StemCell Therapy

June 30, 2017

Uncovering rare susceptibility variants that contribute to the causes of complex diseases requires large sample sizes and massively parallel sequencing technologies. These sample sizes, often made up of exome and genome data from tens to hundreds of thousands of individuals, are often too large for current analytical tools to process. A team at Baylor College of Medicine, led by Dr. Suzanne Leal, professor of molecular and human genetics, has developed new software called SEQSpark to overcome this processing obstacle. A study on the new technology appears in The American Journal of Human Genetics.

"To handle these large data sets, we built the SEQSpark tool based on the commonly used Spark program, which allows SEQSpark to utilize multiple processing platforms to increase the speed and efficiency of performing data quality control, annotation and rare variant association analysis," Leal said.

To test and validate the versatility and speed of SEQSpark, Leal and her team analyzed benchmarks from the whole genome sequence data from the UK10K, testing specifically for waist-to-hip ratios.

"The analysis and related tasks took about one and a half hours to complete, in total. This includes loading the data, annotation, principal components analysis and single and rare variant aggregate association analysis for the more than 9 million variants present in this sample set," explained Di Zhang, a postdoctoral associate in the Leal lab at Baylor and first author on the paper.

To evaluate SEQSpark's performance in a larger data set, Leal and the research team generated 50,000 simulated exomes. The SEQSprak program ran the analysis for a quantitative trait using several variant aggregate association methods in an hour and forty-five minutes.

When compared to other variant association tools, SEQSpark was consistently faster, reducing computation to a hundredth of the time in some cases.

"What is unique about SEQSpark is that it is scalable, and smaller labs can run it without super specific hardware, and it can also be run in a multi-server environment to increase its speed and capacity for large genetic data sets," Zhang said. "It is ideal for large-scale genetic epidemiological studies and is highly efficient from a computational standpoint."

"We see this software as being very useful as the demand for the analysis of massively parallel sequence data grows. SEQSpark is highly versatile, and as we analyze increasingly large sets of rare variant data, it has the potential to play a key role in furthering personalized medicine," Leal said.

In the future, Leal and her team will continue to test and increase SEQSpark's capabilities and will be analyzing soon data sets that have 500,000 samples or more.

Explore further: Genetic test for familial data improves detection genes causing complex diseases such as Alzheimer's

More information: Di Zhang et al. SEQSpark: A Complete Analysis Tool for Large-Scale Rare Variant Association Studies using Whole-Genome and Exome Sequence Data, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.05.017

A team of researchers at Baylor College of Medicine has developed a family-based association test that improves the detection in families of rare disease-causing variants of genes involved in complex conditions such as Alzheimer's. ...

Precision medicine, which utilizes genetic and molecular techniques to individually tailor treatments and preventative measures for chronic diseases, has become a major national project, with President Obama launching the ...

A multi-institutional team of researchers has sequenced the DNA of 6,700 exomes, the portion of the genome that contains protein-coding genes, as part of the National Heart, Lung and Blood Institute (NHLBI)-funded Exome Sequencing ...

(Medical Xpress)Via genetic analysis, a large international team of researchers has found rare, damaging gene variants that they believe contribute to the risk of a person developing schizophrenia. In their paper published ...

Human genome sequencing costs have dropped precipitously over the last few years, however the analytical ability to meet the growing demand for making sense of large data sets remains as a bottleneck. With the introduction ...

Researchers at EMBL-EBI have developed a new approach to studying the effect of multiple genetic variations on different traits. The new algorithm, published in Nature Methods, makes it possible to perform genetic analysis ...

Following up on findings from a an earlier genome-wide association study (GWAS) of type 2 diabetes (T2D) in Latinos, researchers from the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) traced ...

Although the basic outlines of human hearing have been known for years - sensory cells in the inner ear turn sound waves into the electrical signals that the brain understands as sound - the molecular details have remained ...

Using a new skin cell model, researchers have overcome a barrier that previously prevented the study of living tissue from people at risk for early heart disease and stroke. This research could lead to a new understanding ...

The first results from a functional genetic catalogue of the laboratory mouse has been shared with the biomedical research community, revealing new insights into a range of rare diseases and the possibility of accelerating ...

Whole genome sequencing involves the analysis of all three billion pairs of letters in an individual's DNA and has been hailed as a technology that will usher in a new era of predicting and preventing disease. However, the ...

Researchers have found that genes for coronary heart disease (CAD) also influence reproduction, so in order to reproduce successfully, the genes for heart disease will also be inherited.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

The rest is here:
Researchers build SEQSpark to analyze massive genetic data sets - Medical Xpress

Born in August, Charlie Gard has a rare genetic disorder known as mitochondrial DNA depletion syndrome. Caused by a genetic mutation, it leads to weakened muscles and organ dysfunction, among other symptoms, with a poor prognosis for most patients.

Charlie is on life support and has been in the intensive care unit at the Great Ormond Street Hospital for Children in London since October. His doctors wish to take him off life support, but his parents disagree.

"The domestic courts concluded that it would be lawful for the hospital to withdraw life sustaining treatment because it was likely that Charlie would suffer significant harm if his present suffering was prolonged without any realistic prospect of improvement, and the experimental therapy would be of no effective benefit," a press release from the court announcing the decision said.

Charlie's parents appealed to the UK Supreme Court to decide the best interests of their child. After they lost that appeal, the 10-month-old was due to have his life support switched off at the end of the day June 13.

Gard and Yates then filed a request with the European Court of Human Rights, an international court based in Strasbourg, France, to consider the case.

The original ruling to provide life support until June 13 was extended by European Court of Human Rights initially for one week, until June 19. Rather than making a decision then, the court granted a three week-extension, until July 10, to allow for a more informed decision by the court. That extension ended Tuesday with the courts decision.

However, parental rights are not absolute, and in cases in which doctors and parents disagree, the courts may exercise objective judgment in a child's best interest.

In April, a judge tasked with ruling on the impasse between doctors and parents decided in favor of the Great Ormond Street Hospital doctors. In his decision, Justice Francis said life support treatment should end so Charlie could die with dignity.

The boy's parents challenged this ruling in May, yet it was upheld by a Court of Appeal. Three Supreme Court justices later dismissed another challenge from the couple.

Since Charlie's birth, "his condition has deteriorated seriously," the UK Supreme Court stated in a decision June 8; his brain is severely affected, and "he cannot move his arms or legs or breathe unaided."

On this basis, the court ruled that the child's life support should be switched off June 13, but the family appealed to the European court.

Charlie's parents argued that the UK courts gave insufficient weight to their own human rights, and some of Charlie's human rights, in their decision-making, Wilson said.

After the European court's ruling to extend the deadline while judges considered the case further, the Supreme Court told doctors it "would not be unlawful" to continue to provide life support.

After the extension, a Supreme Court hearing was requested by the government and the Great Ormond Street Hospital for Children, which did not know whether the Strasbourg court order was legally binding in the UK, Wilson explained.

"There was also a secondary issue, which was that (Great Ormond Street Hospital's) legal representatives were concerned that at present, doctors did not have sufficient legal clarity about what they can and can't do if Charlie's condition deteriorates," Wilson said. "So this court was also invited to consider whether any UK court, and if so which court, should handle that matter."

In fact, it has never been used to treat this form of mitochondrial DNA depletion syndrome, according to the British ruling, though it has proved beneficial to patients with a different form of the disease.

"He literally has nothing to lose but potentially a healthier, happier life to gain," they said.

Parents are rightly at the "heart" of decisions made about life-sustaining treatment for critically ill children, noted Dominic Wilkinson, director of medical ethics at the Oxford Uehiro Centre.

"Sadly, reluctantly, doctors and judges do sometimes conclude -- and are justified in concluding -- that slim chances of life are not always better than dying." Sometimes, the "best that medicine can do" -- and the most ethical decision -- is to provide comfort and to avoid painful and unhelpful medical treatments, he wrote.

The court said the decision was meticulous, noting that they spoke with Charlie's health care providers, independent experts, experts recommended by the family, and Charlie's parents to inform the ruling. In the end, the press released said they determined, "it was most likely Charlie was being exposed to continued pain, suffering and distress and that undergoing experimental treatment with no prospects of success would offer no benefit, and continue to cause him significant harm."

CNN's Stephanie Halasz, Debra Goldschmidt and Judith Vonberg contributed to this report.

See the article here:
Court rules hospital can withdraw life support for sick baby Charlie Gard - CNN International

June 29, 2017 Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Scientists have had limited success at identifying specific inherited genes associated with prostate cancer, despite the fact that it is one of the most common non-skin cancers among men. Researchers at University of Utah Health studied prostate cancer patients with multiple cancer diagnoses, many who would not be recommended for genetic tests following current guidelines, to identify genetic mutations that may influence cancer treatment and cancer risk assessment for family members. Their findings are reported in the June issue of the journal Cancer.

"We commonly use a combination of a patient's personal and family cancer histories to identify those individuals who may have a mutation in a gene that predisposes that individual to developing cancers," said Patrick Pili, M.D., medical oncology fellow at the University of Texas MD Anderson Cancer Center. "Testing for hereditary cancers impacts not only the patient with cancer but also potentially the cancer screening and health outcomes of their entire family, but many prostate cancer patients do not meet the current guidelines to test for genetic cancer heritability."

Pili was part of a research team led by Kathleen Cooney, M.D., chair of the Department of Internal Medicine at U of U Health and a Huntsman Cancer Institute investigator, who proposed a strategy to identify germline mutations in men selected for the study based on their clinical history not their family history.

The study was highly selective, including 102 patients who had been diagnosed with prostate cancer and at least one additional primary cancer, like melanoma, pancreatic cancer, testicular cancer, or Hodgkin lymphoma.

The researchers examined the frequency of harmful germline mutations in this group of men. These mutations originate on either the egg or sperm and become incorporated into the DNA of every cell in the body of the resulting offspring.

Using next generation sequencing, the researchers found that 11 percent of the patients had a disease-causing mutation in at least one cancer-predisposing gene, which suggests these genetic variations contributed to their prostate cancer. Cooney found no difference in cancer aggressiveness or age of diagnosis compared to patients without these mutations.

In addition, a certified genetic counselor and co-investigator Elena Stoffel, M.D., University of Michigan Comprehensive Cancer Center, reviewed personal and family histories from each patient to determine whether they would meet clinical genetic testing guidelines. The majority of the men in the study, 64 percent, did not meet current criteria to test for hereditary cancer based on personal and/or family history.

The findings suggest that there are men with heritable prostate cancer-predisposing mutations that are not eligible for genetic screening under current guidelines.

"This is the first paper in which we can show the potential of using a clinical history of multiple cancers, including prostate cancer, in a single individual to identify inherited germline mutations," Cooney said.

The majority of harmful mutations identified were in genes involved in DNA repair.

"These mutations prevent the DNA from healing itself, which can lead to a predisposition for cancer," Cooney said.

This result is also beneficial because drugs like PARP [poly ADP ribose polymerase] inhibitors have a better success rate in treating cancers with the underlying gene mutation associated with DNA repair.

Cooney cautions that this is a small pilot study rather than a broader epidemiological survey, and it consists of a highly specific subset of patients.

"We cannot generalize these findings to the broader population, because we used highly selective criteria to tip us off to patients that may have mutations outside typical hereditary genetic patterns," she said.

The 102 patients included in the study were identified from the University of Michigan's Prostate Cancer Genetics Project, which registers patients who are diagnosed with prostate cancer before age 55 or who have a first- or second-degree relative with prostate cancer. In addition, the research team identified patients from the University of Michigan's Cancer Genetics Registry, which includes individuals with personal or family history suggestive of a hereditary risk of cancer.

"Our findings are in line with those of other studies, suggesting that approximately 1 in 10 men with advanced prostate cancer harbors a genetic variant associated with increased cancer risk," said Stoffel. "While family history is an important tool, there may be better ways to identify patients with genetic risk."

Future studies with larger sample sizes will include sequencing of tumors that will allow investigators to more carefully explore the different features associated with tumors that arise in individuals with germline mutations.

"This approach will help us identify patients at greater risk for aggressive prostate cancer so they can seek earlier screening while pre-symptomatic," Cooney said.

Explore further: Are men with a family history of prostate cancer eligible for active surveillance?

More information: Patrick G. Pili et al. Germline genetic variants in men with prostate cancer and one or more additional cancers, Cancer (2017). DOI: 10.1002/cncr.30817

Journal reference: Cancer

Provided by: University of Utah

Active surveillancecareful monitoring to determine if or when a cancer warrants treatmentis an increasingly prevalent choice for prostate cancer, but it's unclear if the strategy is appropriate for men with a family ...

Inherited mutations in genes that function to repair DNA may contribute to metastatic prostate cancer more than previously recognized, according to a study out today in the New England Journal of Medicine. Though infrequent ...

African-American men develop prostate cancer more often than other men, and it tends to be more deadly for this population. Some of the differences seem to be due to socioeconomic factors, but scientists wondered whether ...

(HealthDay)A man's risk of aggressive and fatal prostate cancer may be heavily influenced by gene mutations previously linked to breast and ovarian cancer in women, a trio of new studies suggests. Findings from the studies ...

Scientists are reporting a test which can predict which patients are most at risk from aggressive prostate cancer, and whether they suffer an increased chance of treatment failure. This test, reported at the European Association ...

A form of genetic variation, called differential RNA splicing, may have a role in tumor aggressiveness and drug resistance in African American men with prostate cancer. Researchers at the George Washington University (GW) ...

While mutations in protein-coding genes have held the limelight in cancer genomics, those in the noncoding genome (home to the regulatory elements that control gene activity) may also have powerful roles in driving tumor ...

A molecular test can pinpoint which patients will have a very low risk of death from breast cancer even 20 years after diagnosis and tumor removal, according to a new clinical study led by UC San Francisco in collaboration ...

Scientists have had limited success at identifying specific inherited genes associated with prostate cancer, despite the fact that it is one of the most common non-skin cancers among men. Researchers at University of Utah ...

Cancerous tumors are formidable enemies, recruiting blood vessels to aid their voracious growth, damaging nearby tissues, and deploying numerous strategies to evade the body's defense systems. But even more malicious are ...

Leukemia researchers led by Dr. John Dick have traced the origins of relapse in acute myeloid leukemia (AML) to rare therapy-resistant leukemia stem cells that are already present at diagnosis and before chemotherapy begins.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read this article:
Researchers propose new approach to identify genetic mutations in ... - Medical Xpress

June 26, 2017 Credit: CC0 Public Domain

Between 15 and 20 percent of black people carry a genetic mutation that puts them at risk for certain chronic kidney disease, but only about half of them develop the illness - a variance that long has puzzled researchers. Now a study has found that the gene mutation's toxic effects require higher than normal levels of a protein called suPAR to trigger the onset and progression of the disease.

The results of the study, published in a research article in the journal Nature Medicine today, could lead soon to new treatments for chronic kidney disease that target these risk factors, according to Dr. Jochen Reiser, the senior author of the paper. Reiser is the chairperson of the Department of Internal Medicine and Ralph C. Brown MD Professor of Medicine at Rush University Medical Center, Chicago.

Chronic kidney disease - or CKD for short - is a progressive failure of function that prevents kidneys from fulfilling their role filtering waste from the blood stream. Nearly 17 percent of people in the U.S. have chronic kidney disease, and approximately 4 percent require dialysis and/or a kidney transplant due to kidney failure. Currently, there are no drugs that can treat CKD in an effective way.

Study analyzed samples from more than 1,000 people with genetic risk for CKD

For the study recounted in the Nature Medicine paper, Reiser worked with a team that included researchers at Emory University, Harvard University, Johns Hopkins University, the National Institute of Health, Ruprecht Karls University of Heidelberg, the Israel Institute of Technology and others. Together, they looked at two well-known genetic risk factors for CKD in black people, the mutated G1 or G2 variations in the gene known as apolipoprotein L1 (APOL1). To be at risk for developing CKD, an individual must have inherited two of these gene variants, one from each parent.

The study analyzed blood samples for suPAR levels, screened for APOL1 gene mutations and measured kidney function from two separate cohorts of black patients - 487 people from the Emory Cardiovascular Biobank, 15 percent of whom had a high-risk APOL1 genotype; and 607 from the multi-center African American Study of Kidney Disease and Hypertension, including 24 percent with the high-risk mutation.

Using these two large, unrelated cohorts, the researchers found that plasma suPAR levelsindependently predict renal function decline in individuals with two copies of APOL1 risk variants. APOL1-related risk is reduced by lower levels of plasma suPAR and strengthened by higher levels.

The team then went on and used purified proteins to study if suPAR and APOL1 bind to each other. They found that the mutated G1 and G2 variant did so particularly well on what's known as a receptor on the surface of kidney cells, in this case the suPAR activated receptor alphavbeta3 integrin. "This binding appears to be a key step in the disease onset" adds Dr. Kwi Hye Ko, a scientist at Rush and the study's co-first author.

This binding causes kidney cells to change their structure and function, permitting disease onset. Using cell models and genetically engineered mice, the authors then could reproduce kidney disease changes upon expression of APOL1 gene variants, but the disease required the presence suPAR.

Without elevated suPAR levels, genetic mutation much less likely to trigger disease

Everybody has suPAR, which is produced by bone marrow cells, in their blood, with normal levels around 2400 picogram per milliliter (pg/ml). As levels of suPAR rise, risk for kidney disease rises in turn.

Patients with levels above 3000 picogram per milliliter carry a much higher risk for kidney disease in the general population. Black people are particularly at risk, given the study's finding that suPAR activates its receptor on kidney cells that then attract the APOL1 risk proteins. Over time, these assaults can damage and eventually destroy the kidney.

On the other hand, without high levels of suPAR, the ability of the genetic mutation of APOL1 to exert its damaging effects is impaired, which helps identify patients in most need of suPAR lowering or future anti-suPAR therapy.

"Patients with APOL1 mutations who don't get kidney disease have more commonly low suPAR levels," said Dr. Salim Hayek, co-first author of the paper and a cardiologist at Emory University School of Medicine. "The suPAR level needs to be high to activate the mechanism in the kidney that enables APOL1 proteins" and set off the chain of events the genetic mutation can trigger.

suPAR 'is to the kidneys as cholesterol is to the heart'

Like some other pathological gene mutations, the APOL1 variations may have persisted in the population, in this case in Africa, because they could protect people from infection with the parasites known as trypanosome. explained Sanja Sever, PhD, co-correspondent author of the paper and associate professor of medicine at Harvard Medical School. In the United States, however, fighting parasitic trypanosomes isn't a significant concern, while lifestyle and environmental pressures such as obesity promote the rise in suPAR levels. This scenario sets up people for high risk of kidney disease.

Reiser has spent his career studying a scarring type of chronic kidney disease, focal segmental glomerulosclerosis. In past studies, he discovered that suPAR not only is a marker for kidney disease, but also a likely cause.

"What we are learning today is that suPAR in a general way is to kidneys what cholesterol is to the heart, a substance that can cause damage if levels rise too high, or a substance that can likely make many forms of kidney disease worse," Reiser says. "Based on these fundamental insights, suPAR level testing may become a routine test at many institutions around the world."

Like cholesterol, suPAR levels vary from person to person. Some environmental factors can contribute significantly to elevated suPAR levels. "Lifestyle is a big factor, bigger than we thought," Reiser says.

Smoking, weight gain and even frequent infections can add up and send suPAR to dangerous heights. Weight loss and smoking cessation can help bring levels down, but once elevated, suPAR may not recede to a healthy level again, said Dr. Melissa Tracy, co-author of the study and an associate professor of cardiology at Rush. People at genetic risk for kidney disease should aim to live a healthy life to keep suPAR levels low.

Explore further: Circulating blood factor linked with a leading cause of kidney failure

More information: A tripartite complex of suPAR, APOL1 risk variants and v3 integrin on podocytes mediates chronic kidney disease, Nature Medicine (2017). DOI: 10.1038/nm.4362

Patients with a disease that is a leading cause of kidney failure tend to have high levels of a particular factor circulating in their blood, according to a study appearing in an upcoming issue of the Journal of the American ...

A protein known as suPAR has been identified in recent years as both a reliable marker for chronic kidney disease and a pathogen of the often deadly condition. Its place of origin in the human body, however, has been a mysteryuntil ...

Make room, cholesterol. A new disease marker is entering the medical lexicon: suPAR, or soluble urokinase-type plasminogen activator receptor. A study in the New England Journal of Medicine shows that suPAR, a circulating ...

African Americans have a heightened risk of developing chronic and end-stage kidney disease. This association has been attributed to two common genetic variants - named G1 and G2in APOL1, a gene that codes for a human-specific ...

New research investigates the ties between certain genetic variants and kidney disease in African Americans. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), suggest ...

Transplanted kidneys may not function long-term if they come from donors with variants in a particular gene, according to a study that will be presented at ASN Kidney Week 2014 November 11-16 at the Pennsylvania Convention ...

By age 2, most children have been infected with respiratory syncytial virus (RSV), which usually causes only mild cold symptoms. But people with weakened immune systems, such as infants and the elderly, can face serious complications, ...

Even if hospital workers practice perfect hand hygiene, MRSA can still spread among babies in the NICU, according to new research led by a Drexel University researcher.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are resistant to multiple antibiotics and commonly cause skin infections that can lead to more serious or life-threatening infection in other parts of the body. ...

In a new study, researchers inoculated mice with a new DNA vaccine candidate (pVAX1-D1ME) in order to evaluate its efficiency. They found that the vaccine candidate was able to induce persistent humoral and cellular immune ...

Despite the potentially severe consequences of illness and even death, only about 40 percent of adults in the United States receive flu shots each year; however, researchers believe a new self-administered, painless vaccine ...

A new study has found that flu evolution within some individuals can hint at the virus's eventual evolutionary course worldwide.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See more here:
Catalyst for genetic kidney disease in black people identified - Medical Xpress

Picture a time in the not-too-distant future when whole genome sequencing is routine. A time when, before babies even learn to talk, their parents will have the ability to learn what the future may have in store for their offspring: Is their little girl predisposed to getting breast cancer? Will their happy-go-lucky son one day develop Alzheimer's?

"There is no doubt in my mind that, in addition to going in and having blood chemistry done, you're gonna have DNA sequencing done, too. It will be there at some point," says Nicholas Schork, a quantitative geneticist at the J. Craig Venter Institute in La Jolla, California, who has studied genomic medicine for more than three decades. "We can debate about the timeline, but it'll become routine."

The hope is that genetic testing will make health care more effective by allowing doctors and patients to focus on areas that need attention the patient's genetic "vulnerabilities." At the same time, patients may learn of areas where they won't need to be quite as vigilant. And treatments could, in turn, be perfectly tailored to a patient's specific needs.

But as with any significant and broadly applicable medical advance, there are questions. For example, should patients learn that they carry markers for currently incurable genetic diseases, or that they are at high risk for developing a condition like Alzheimer's, which has no effective treatment? And just who owns all that genetic data? Who will have access to it?

Even with important questions left unanswered, health educators are moving forward to take advantage of the promises genetic testing offers. Washington State University's new Elson S. Floyd College of Medicine has announced it is partnering with Arivale, a Seattle-based company that conducts whole genome sequencing, to help complete a portrait of a person a "portrait" that can be used to promote wellness over that individual's entire lifespan. Every member of the school's inaugural class will have the opportunity to undergo testing, which will also include blood tests and a lifestyle evaluation. Then, over the next year, Arivale's team of nurses and dietitians will provide individually tailored follow-up, based on each individual's risks and goals. It's a unique partnership, made possible in large part because the medical school is new, with its first class of students starting in 2017.

Allowing the medical students to experience genetic testing firsthand is just part of the goal. "We need physicians that understand it well enough that they can make it better going forward," says John Tomkowiak, founding dean of WSU's College of Medicine. "That's where our students are going to be uniquely positioned."

WHAT GENES TELL US

Genetic testing already provides important information about a person's health or their heritage. Hospitals screen newborn babies for certain genetic disorders, and in some cases, tests can detect disorders before birth. And diagnostic testing can confirm, or rule out, many disorders in adults.

Testing doesn't have to be ordered by a physician. For $200, you can provide a saliva sample, mail it back to 23andMe.com and find out not only your ancestry, but also your risks for a number of diseases, including Alzheimer's and Parkinson's. Ancestry.com offers a glimpse into your heritage for $99. Color.com claims to reveal your risk for the most common hereditary cancers, and even offers "complimentary genetic counseling" for a $249 fee.

But if genetic testing is to revolutionize the health care industry, as many have promised, there's still a ways to go. "The technology is at the beginning stages," says Thomas May, a faculty researcher for the HudsonAlpha Institute for Biotechnology.

Companies like 23andMe offer genetic tests that may provide information about some genetic disorders from currently known genetic variants. But whole genome sequencing is different; it will reveal all your individual genetic variants.

How valuable is that information? There are a relatively small number of conditions that researchers are confident result from a specific genetic variant, May says. For example, there is one variant that researchers have found is associated with an increased risk of developing breast or ovarian cancer. A genetic test that shows an increased risk for breast cancer is considered an "actionable" outcome, meaning there are things you can do to prevent the outcome, like beginning mammograms earlier. Though there are more than 50 actionable outcomes like that, it's still a relatively small number.

Adding to the confusion is the fact that not everyone who develops breast cancer actually has the genetic variant in fact, May says only about 10 percent do. So even if testing shows that you don't have the "breast cancer gene," that doesn't mean it's OK to stop getting mammograms.

"Most variants and correlations are of that type: We can't say for certain if you're gonna get a disease," May says.

Doctors are mixed about whether genetic testing is currently having a real impact on patients. In a May survey conducted by the Medscape Physician Oncology Report on Genomics Testing, 71 percent of oncologists surveyed felt that genetic testing was either "very" or "extremely" important to the oncology field. At the same time, 61 percent said that, currently, fewer than a quarter of their patients would actually benefit from genetic testing.

The number of diseases with "actionable" outcomes will inevitably grow, as more people are tested and more data becomes available. But this leaves deeper questions, says Schork, the quantitative geneticist. A company or health care provider would likely give patients information about diseases that can be prevented or cured. If someone is predisposed to obesity, for instance, then he or she can elect to receive targeted care to reduce that risk.

But what about diseases that, right now, are incurable?

Take Huntington's disease, a genetic disorder that breaks down nerve cells in the brain. It's rare, but it's a "hideous way to die," Schork says. A person can be screened at the age of 25 and be found to carry the Huntington's gene, but there's debate about whether or not that information should be shared with a client or not. The same goes for genetic variants related to Alzheimer's disease.

"If there's nothing they can do about it, then there's a concern about whether or not that information should be imparted," Schork says.

When the Food and Drug Administration ordered 23andMe to stop telling customers their odds of contracting diseases in 2013, Harvard Medical School genetics professor Robert Green and Laura Beskow, a professor at Duke University's Institute for Genome Sciences and Policy, argued against the FDA. They cited a number of studies showing that direct-to-consumer genetic testing does not cause a large percentage of customers despair. In an interview with the New York Times in April, Green said the potential for distress based on results of a genetic test for Alzheimer's was "much smaller than anticipated."

Another question: Who really owns the DNA data that is being collected from willing users of genetic testing? Consider Myriad, a company that offers genetic testing both to help determine cancer risk and design better treatment plans for patients who already have cancer. The company has something that "others do not," Schork says: insight into which genetic variants predispose women to breast cancer.

What Myriad is really selling, then, is not the genetic test itself, but access to insights it has gained through mining its database, insights that can be leveraged into whatever level of payment the company decides to charge.

It's potentially critical information that could help save a life, and some argue that the data should be in the public domain not held by a private company.

"There have been huge debates about whether the community should challenge the monopoly that Myriad has," Schork says. "There are many groups out there that would like to counteract the monopoly Myriad has, by building public domain data sets."

JUST ONE TOOL

"Genetic testing is not a blueprint. It's really not," says Jennifer Lovejoy, chief translational science officer for Arivale. "Genes are really just one factor the environment, diet, exercise, pollutants and even emotional state have a big impact on genes."

That's why Arivale not only collects genetic information on each client, but also evaluates various blood tests and lifestyle factors to create a "dense data cloud" of information about a patient.

"That is the grand vision: that everybody would have these dense, dynamic data clouds, and understand the choices that will be optimal to optimize wellness and avoid disease," says Lovejoy.

Arivale touts the success stories among its nearly 2,000 clients. One client found out he had a gene associated with high sensitivity to saturated fat, giving him a better indication of an appropriate diet that helped him lose weight. Another client discovered that his genes may have an impact on his cholesterol. Another learned he was at risk of developing diabetes.

Ideally, this type of preventive care will soon be covered by insurance, Lovejoy says. The thinking is that preventing disease will bring down the cost of health care overall, making insurers likely to cover more preventive care, "but we have to prove it," Lovejoy says. Researchers are conducting studies and trials to do just that, and if they can prove it, then genetic testing could soon be routine in health care.

"If you think about what health care should mean, it should mean, one, the ability to deal with disease and that's what everyone does today," Arivale co-founder Leroy Hood said at a press conference in April announcing the company's partnership with WSU. "But two, it should mean the ability to optimize wellness for each individual. That is, improving their health and/or letting them avoid disease." That's a concept Hood calls "scientific wellness, and he thinks it could lead to "a whole new health care industry in the future."

Tomkowiak, of WSU's College of Medicine, agrees: "The concept of scientific wellness has the potential to disrupt the entire industry by shifting the cost curve, by keeping people healthier and reducing the cost of health care overall."

Regardless of whether or not Arivale becomes an industry leader, Tomkowiak believes that the practice of medicine will be fundamentally altered in the near future.

"We absolutely believe that seven years from now, the practice of scientific medicine and scientific wellness will be common," he says. "Instead of being behind the curve, we want... to be leading this effort."

For about $3,500, clients can sign up for Arivale's program. The fee includes whole genome sequencing, which is also available from other sources. So how do Arivale clients achieve "scientific wellness"? Here are the elements of their program:

Welcome package: Clients get a welcome package with a Fitbit to track sleep, activity and heart rate. The package asks for information to help understand a client's bacteria in their gut, and asks for a sample of saliva to measure a person's stress level.

Online test: Clients take a series of online assessments about their goals, health history, lifestyle, stress, personality and happiness.

Call from coach: You'll talk to a coach who will get to know what you want to accomplish and give you a personalized action plan.

Labs: You'll take blood tests so your coach can understand your current health. While you're there, they'll take your vital signs.

A picture emerges: The various test create a picture of you, which an Arivale coach will use to provide a step-by-step plan to "optimize your wellness," according to the company.

Follow-up: You're not done yet. You'll be contacted by your coach regularly to review your action plan, and Arivale will provide reports on how you're progressing. Every six months, you'll complete another set of clinical labs.

Source: arivale.com/your-journey

Read more here:
What's In Your Genes? - Pacific Northwest Inlander

Pacific Standard

The Future of Medicine Depends on Protections for Pre-Existing Conditions Pacific Standard Biomedical researchers can see a future where genetic tests are used to treat and prevent many diseases before major symptoms even present themselves. But that future won't be possible without strong insurance protections for pre-existing conditions.

View post:
The Future of Medicine Depends on Protections for Pre-Existing Conditions - Pacific Standard

This file photo shows doctors at Memorial Sloan Kettering Cancer Center in New York City.

An experimental cancer medicine called larotrectinib has shown promise treating a diverse range of cancers in people young and old, researchers said at a major cancer conference in the United States.

The treatment targets a genetic abnormality which is often found in rare cancers - including salivary gland cancer, juvenile breast cancer, and a soft tissue cancer known as infantile fibrosarcoma - which are particularly difficult to treat.

This abnormality also occurs in about 0.5 percent to one percent of many common cancers.

In the study released at the American Society of Clinical Oncology conference, 76 percent of cancer patients - both children and adults with 17 different kinds of cancer - responded well to the medicine.

A total of 79 percent were alive after one year. The study is ongoing.

Twelve percent went into complete remission from their cancer.

The clinical trial included 55 patients - 43 adults and 12 children. All had advanced cancers in various organs, including the colon, pancreas and lung, as well as melanoma.

"These findings embody the original promise of precision oncology: treating a patient based on the type of mutation, regardless of where the cancer originated," said lead study author David Hyman, chief of early drug development at Memorial Sloan Kettering Cancer Center in New York.

"We believe that the dramatic response of tumors with TRK fusions to larotrectinib supports widespread genetic testing in patients with advanced cancer to see if they have this abnormality."

Made by Loxo Oncology Inc., larotrectinib is a selective inhibitor of tropomyosin receptor kinase (TRK) fusion proteins.

TRK proteins are a product of a genetic abnormality when a TRK gene in a cancer cell fuses with one of many other genes, researchers said.

The US Food and Drug Administration has not yet approved the treatment for widespread use.

The treatment was well tolerated by patients, and the most common side effects were fatigue and mild dizziness.

"If approved, larotrectinib could become the first therapy of any kind to be developed and approved simultaneously in adults and children, and the first targeted therapy to be indicated for a molecular definition of cancer that spans all traditionally-defined types of tumors," said Hyman.

(Source:AFP)

Read more:
New cancer medicine targets rare genetic flaw - Press TV

SUNDAY, June 4, 2017 (HealthDay News) -- A twice-daily pill could help some advanced breast cancer patients avoid or delay follow-up sessions of chemotherapy, a new clinical trial reports.

The drug olaparib (Lynparza) reduced the chances of cancer progression by about 42 percent in women with breast cancer linked to BRCA1 and BRCA2 gene mutations, according to the study.

Olaparib delayed cancer progression by about three months. The drug also caused tumors to shrink in three out of five patients who received the medication, the researchers reported.

"Clearly the drug was more effective than traditional chemotherapy," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"This is a group where a response is more difficult to obtain -- a young group with a more aggressive form of cancer -- and nonetheless we saw a close to 60 percent objective response rate," he said.

The study was funded by AstraZeneca, the maker of Lynparza.

Olaparib works by cutting off the avenues that malignant cancer cells use to stay alive, said lead researcher Dr. Mark Robson. He's a medical oncologist and clinic director of Clinical Genetics Service at Memorial Sloan Kettering Cancer Center in New York City.

The drug inhibits PARP, an enzyme that helps cells repair damaged DNA, Robson said.

Normal cells denied access to PARP will turn to the BRCA genes for help, since they also support the repair of damaged DNA, Robson said.

But that "backup capability" is not available to breast cancer cells in women with BRCA gene mutations, Robson said.

"When you inhibit PARP, the cell can't rescue itself," Robson said. "In theory, you should have a very targeted approach, one specifically directed at the cancers in people who have this particular inherited predisposition."

Olaparib already has been approved by the U.S. Food and Drug Administration for use in women with BRCA-related ovarian cancer. Robson and his colleagues figured that it also should be helpful in treating women with breast cancer linked to this genetic mutation.

The study included 302 patients who had breast cancer that had spread to other areas of their body (metastatic breast cancer). All of the women had an inherited BRCA mutation.

They were randomly assigned to either take olaparib twice a day or receive standard chemotherapy. All of the patients had received as many as two prior rounds of chemotherapy for their breast cancer. Women who had hormone receptor-positive cancer also had been given hormone therapy.

After 14 months of treatment, on average, people taking olaparib had a 42 percent lower risk of having their cancer progress compared with those who received another round of chemotherapy, Robson said.

The average time of cancer progression was about seven months with olaparib compared with 4.2 months with chemotherapy.

Tumors also shrank in about 60 percent of patients given olaparib. That compared with a 29 percent reduction for those on chemotherapy, the researchers said.

Severe side effects also were less common with olaparib. The drug's side effects bothered 37 percent of patients compared with half of those on chemo. The drug's most common side effects were nausea and anemia.

"There were fewer patients who discontinued treatment because of toxicity compared to those who received chemotherapy," Robson said. "Generally it was pretty well tolerated."

Only about 3 percent of breast cancers occur in people with BRCA1 and BRCA2 mutations, the researchers said in background notes.

Despite this, the results are "quite exciting," said Dr. Julie Fasano, an assistant professor of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

Olaparib could wind up being used early in the treatment of metastatic breast cancer as an alternative to chemotherapy, and future studies might find that the drug is effective against other forms of breast cancer, Fasano said.

"It may be a practice-changing study, in terms of being able to postpone IV chemotherapy and its associated side effects" like hair loss and low white blood cell counts, Fasano said.

Lichtenfeld noted that olaparib also places less burden on patients.

"It may be easier for women to take two pills a day rather than go in for regular chemotherapy," Lichtenfeld said. "Clearly, this is a treatment that will garner considerable interest.

The findings were scheduled to be presented Sunday at the American Society of Clinical Oncology's annual meeting, in Chicago. The study was also published June 4 in the New England Journal of Medicine.

Go here to see the original:
Drug Helps Fight Breast Tumors Tied to 'Cancer Genes' - Sioux City Journal

A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibility to a disease refers to a genetic predisposition to a health problem,[1] which may eventually be triggered by particular environmental or lifestyle factors, such as tobacco smoking or diet. Genetic testing is able to identify individuals who are genetically predisposed to certain diseases.

Predisposition is the capacity we are born with to learn things such as language and concept of self. Negative environmental influences may block the predisposition (ability) we have to do some things. Behaviors displayed by animals can be influenced by genetic predispositions. Genetic predisposition towards certain human behaviors is scientifically investigated by attempts to identify patterns of human behavior that seem to be invariant over long periods of time and in very different cultures.

For example, philosopher Daniel Dennett has proposed that humans are genetically predisposed to have a theory of mind because there has been evolutionary selection for the human ability to adopt the intentional stance.[1] The intentional stance is a useful behavioral strategy by which humans assume that others have minds like their own. This assumption allows you to predict the behavior of others based on personal knowledge of what you would do.

E. O. Wilson's book on sociobiology and his book Consilience discuss the idea of genetic predisposition to behaviors

The field of evolutionary psychology explores the idea that certain behaviors have been selected for during the course of evolution.

The Genetic Information Nondiscrimination Act, which was signed into law by President Bush on May 21, 2008,[2] prohibits discrimination in employment and health insurance based on genetic information.

See more here:
Genetic predisposition - Wikipedia

To aid our variant interpretation process, we created an openly-available online tool to efficiently classify variants based on the evidence categories outlined in the article: Richards, et al. Standards and guidelines for the interpretation of sequence variants. 2015. This site displays the evidence categories and descriptions from Table 3 and Table 4 with simple checkboxes for selecting appropriate criteria. The site then incorporates the algorithm in Table 5 to automatically assign the pathogenicity or benign impact based on the selected evidence categories. Since our process often requires analyzing multiple variants per patient, we have also allowed the option of aggregating each variant into an exportable table at the foot of the website for easy documentation of the variant review process for our records. Although this tool is based on the ACMG/AMP Standards and Guidelines, it is not affiliated with ACMG, AMP, or any of the authors of the publication.

_ PVS1 null variant (nonsense, frameshift, canonical 1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease

_ PS1 Same amino acid change as a previously established pathogenic variant regardless of nucleotide change _ PS2 De novo (both maternity and paternity confirmed) in a patient with the disease and no family history _ PS3 Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product _ PS4 The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls _ PP1 (Strong evidence) Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease

_ PM1 Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation _ PM2 Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium _ PM3 For recessive disorders, detected in trans with a pathogenic variant _ PM4 Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants _ PM5 Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before _ PM6 Assumed de novo, but without confirmation of paternity and maternity _ PP1 (Moderate evidence) Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease

_ PP1 Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease _ PP2 Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease _ PP3 Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) _ PP4 Patients phenotype or family history is highly specific for a disease with a single genetic etiology _ PP5 Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation

_ BP1 Missense variant in a gene for which primarily truncating variants are known to cause disease _ BP2 Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern _ BP3 In-frame deletions/insertions in a repetitive region without a known function _ BP4 Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.) _ BP5 Variant found in a case with an alternate molecular basis for disease _ BP6 Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation _ BP7 A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved

_ BS1 Allele frequency is greater than expected for disorder _ BS2 Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age _ BS3 Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing _ BS4 Lack of segregation in affected members of a family

_ BA1 Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium

_ Sequencing artifact as determined by depth, quality, or other previously reviewed data

Download Table as CSV

Please note that the text of the variant evidence has been pulled directly from Richards, et al. Genet Med. 2015 May;17(5). This site does not claim authorship of any of the variant evidence descriptions.

This tool is based on the published ACMG/AMP Standards and Guidelines [Genet Med (2015)]. Anyone using this tool should be familiar with that publication. Individuals or institutions choosing to use this tool for clinical variant classification purposes assume legal responsibility for the consequences of its use. The authors make no warranty, express or implied, nor assume any legal liability or responsibility for any purpose for which the tool is used.

Please cite the following when using this tool in publications: Kleinberger J, Maloney KA, Pollin TI, Jeng LJ. An openly available online tool for implementing the ACMG/AMP standards and guidelines for the interpretation of sequence variants. Genet Med. 2016 Mar 17. doi: 10.1038/gim.2016.13. [Epub ahead of print] PubMed PMID: 26986878.

Read more:
Genetic Variant Interpretation Tool | University of ...

Imagine a world where an ambulance arrives to pick you up, not after a heart attack but before it happens, based on a signal sent from a device on your arm via your mobile phone. This sounds like the stuff of science fiction but could become a reality. It is all part of focusing healthcare more on prevention and less on cure. You dont wait for your car to break down before getting it repaired; you have it serviced and act on warning signs. Similarly, with healthcare, prevention is cheaper, more effective and less traumatic.

Another major change is a shift from a one size fits all approach to one tailored to individuals. Most medical treatments are designed for the average patient, and are successful for some but not others. Advances in what is called precision medicine will allow treatments to be tailored to characteristics, such as a persons genetic makeup or the genetic profile of a tumour.

The science that makes possible this combination of prevention and tailoring is genomics. The Human Genome Project mapped the human genome sequence in 2001, which is freely available in public databases. Less well known are the Precision Medicine Initiative in the US (which is creating a health database of a million Americans) and the 100,000 Genomes Project in the UK. These have only become viable because of huge advances in technology and data analytics.

Sequencing the first human genome cost $2.7bn and took 15 years. By 2008, the cost of sequencing had fallen to about $10m. Now sequencing can be done in a few days, with analysis in a few weeks, at cost of $1,000-$2,000.

Your genome is all the genetic information in your bodys instruction manual, encoded as DNA within the 23 chromosome pairs in cell nuclei. We are all very similar genetically: 99.9% of peoples genes are identical and it is the final tenth of a percent that determines differences like hair colour, build and predisposition to disease. Sequencing therefore has the ability to highlight a greater likelihood (or not) of developing conditions such as heart disease, lung cancer or Alzheimers.

The main aim of the 100,000 Genomes Project is to transform the use of genetics in the NHS. The project is run by Genomics England, a company owned by the Department of Health. It will sequence 100,000 whole genomes, half in people with rare genetic diseases (and close relatives who do not exhibit the disease) and half in patients with cancer. The results will be linked with patients medical records and stored securely and confidentially. By combining this information and allowing authorised researchers to access it, the project aims to provide a diagnosis for some patients with rare diseases and adapt cancer treatments. It will help to develop genomic medicine services for the NHS and support researchers to develop new medicines, therapies and diagnostic tests.

The 100,000 Genomes Project and similar ones around the world are unlikely to help the participants directly as the science of genomics is still in its infancy and there is a yawning gap between what sequencing technology enables us to discover and what doctors can do about it. However, it could provide invaluable data to help their children and grandchildren, as well as saving the NHS billions.

John Thornton is the director of e-ssential Resources and an independent adviser on business transformation, financial management and innovation.

John.Thornton@e-ssentialresources.co.uk

Go here to see the original:
Future medicine is all in the genes - Public Finance

New research published today in Genome Medicine uses large-scale DNA sequencing to identify genetic variants that cause developmental delay, a condition that currently goes undiagnosed in a large number of cases. Here to tell us more is author of the research, Dr. Greg Cooper.

Dr. Greg Cooper 30 May 2017

Developmental delay is associated with impaired cognition and failure to meet developmental milestones.

Developmental delay affects 1-2% of children worldwide. Symptoms often associated with developmental delay include impaired cognition, failure to meet developmental milestones, craniofacial and skeletal abnormalities, autism, and seizures. These disabilities can pose major medical, financial and psychological challenges.

Specific diagnoses for children with developmental delay are in many cases elusive, and the lack of a diagnosis is a major hardship for patients and their families. Inaccurate or unavailable diagnoses can result in years of expensive, invasive, and futile testing that complicates treatment decisions and may also lead to anxiety and emotional distress. Moreover, not knowing the reason for specific developmental delays slows research into improving therapeutic or educational options.

Anna Brooke Ainsworth, diagnosed with Cornelia de Lange syndrome (CDL), a rare genetic developmental disorder

In an effort to end the diagnostic odyssey for children with developmental delay, we have employed large-scale DNA sequencing to identify specific genetic variants that are causally relevant to developmental disabilities. As part of the NHGRI-funded Clinical Sequencing Exploratory Research Consortium, we began enrolling affected children into our study in 2013. Thus far, we have sequenced 371 children who present with developmental delay, and we have found the genetic cause and thus contributed to more precise and definitive clinical diagnoses in 27%.

We also enrolled biological parents when available to facilitate the identification of de novo i.e., present in a child but absent from his/her parents genetic variants, as these are known to be enriched among variants that cause developmental disabilities.

By sequencing the affected child and their parents, we were able in many cases to more efficiently identify the pathogenic variant relevant to their symptoms. In addition, by efficiently revealing relatively short lists of candidate de novo variants, trio sequencing also can greatly improve discovery of novel disease contributions.

That said, through retrospective analysis of proband genetic variants in the absence of parental sequence information, we were able to show that completing sequencing for only the child will often still yield a diagnosis, but will on average require more time and analytical effort when compared to the analysis of a trio.

Reanalysis success is driven by, and dependent upon, data sharing by clinicians and scientists who are also sequencing developmentally delayed patients.

Through our study, we observed that finding a pathogenic variant in an affected child is more challenging when close relatives have a neurological condition. This finding suggests that the underlying genetics in such multiplex families are more complex and harder to interpret than in simplex families, and that this distinction influences the success rate in terms of pathogenic variant discovery.

We also demonstrate that reanalysis over time of data from affected children with no initially identified causal genetic finding will often lead to new findings that considerably improve overall yield. Reanalysis success is driven by, and dependent upon, data sharing by clinicians and scientists who are also sequencing developmentally delayed patients.

Our data underscore the value of whole genome sequencing as an effective first-choice diagnostic tool in patients with developmental disabilities. Further, such sequencing, especially as proband-parent trios, will advance clinical and research progress and reduce the number and length of diagnostic odysseys that continue to impact numerous children and their families.

View the latest posts on the On Medicine homepage

By commenting, youre agreeing to follow our community guidelines.

Go here to see the original:
Finding the genetic causes of developmental delay - BMC Blogs Network (blog)

Sessions/Tracks

On behalf of Conference Series LLC we are pleased to welcome you all to Chicago, Illinois, USA to attend the 10th Global Summit on Toxicology and Applied Pharmacology during July 20-22, 2017

Toxicology 2017 is one of the most significant conferences in the world where it contains many disciplines related to the research work and which are prominent in the field it is a leading platform to debate and acquire about the present and developing research works of Toxicology and Pharmacology. Toxicology 2017 which is scheduled at Chicago, USA influences main and important advances in the field. The conference may lead to long-lasting scientific collaborations.

Track 1: Toxicology and Pharmacology

The connected discipline of toxicology includes the study of the nature and mechanisms of deleterious effects of chemicals on living beings. The study of toxicology as a distinct, yet related, discipline to pharmacology highlights the emphasis of toxicologists in formulating measures aimed at protective public health against exposures associated with toxic materials in food, air and water, as well as hazards that may be related with drugs. The word pharmacology itself comes from the Greek word. Pharmacology not only includes the sighting of drugs, but also the study of their biochemical properties, mechanisms of action, uses and biological effects.

Toxicology Conferences | Pharmacology Conferences | Toxicology and Pharmacology Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; Society of Toxicology; Academy of Toxicological Sciences; American Board of Toxicology; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; EUROTOX; German Society of Toxicology

Track 2: Mechanisms of Toxicity

Mechanisms of toxicity are important in both practical and theory wise. It provides a rational basis for understanding descriptive toxicity data, approximating the possibility that a substance will cause risky effects, establishing measures to avoid or antagonize the toxic effects, designing drugs and industrialized chemicals that are fewer hazardous, and evolving pesticides that are more selectively poisonous for their target organisms.

Toxicity Conferences | Immunotoxicity Conferences | Drug Toxicity Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 5th Immunogenicity & Immunotoxicity Conference on February 6-7, 2017 in San Diego, CA; 2nd International Conference on Pollutant Toxic Ions and Molecules, 6 - 9 November 2017, Lisbon, Portugal; Stem Cells in Drug Discovery & Toxicity Screening, July 10-11, 2017, Boston, USA; 19th International Conference on Predictive Human Toxicity, February 16 - 17, 2017, London, United Kingdom; Predicting Drug Toxicity, June 13-14, 2017, Boston, USA; Academy of Toxicological Sciences; EUROTOX; American Board of Toxicology; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association;

Track 3: Molecular Toxicology

Molecular toxicology, the use of sub-atomic science standards and advancements to preclinical wellbeing appraisal, speaks to a key apparatus for comprehension systems of danger and surveying the dangers connected with toxicities. The utilization of quality expression markers to early stage preclinical security evaluation can possibly affect pipelines in two fundamental zones: lead improvement and issue administration.

Toxicology Conferences | Molecular Conferences | Molecular Toxicology Conferences

International Conference on Molecular Evolution July 18-19, 2016 Bangkok, Thailand; 2nd World Congress on Molecular Genetics and Gene Therapy July 3-5, 2017 Bangkok, Thailand; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; Computational Aspects: Biomolecular NMR (GRS) June 10 - 11, 2017, USA; Association for Molecular Pathology (AMP) April 3-5, 2017, Berlin, Germany; International Conference on Biochemistry and Molecular Biology April 3-5 2017, Munich, Germany; 60th Annual Conference of the Canadian Society for Molecular Biosciences May 16-20, 2017, Ottawa, Canada; Canadian Anatomic and Molecular Pathology, February 2-4, 2017, Whistler, Canada; 2nd International Conference on Pollutant Toxic Ions and Molecules, 6 - 9 November 2017, Lisbon, Portugal; Academy of Toxicological Sciences; American Board of Toxicology; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association;

Track 4: Applied Toxicology

Applied Toxicology deals with the fundamentals in toxicology and risk assessment, including the most important databases. The topics related to Applied Toxicology are Medicinal Chemistry, Biochemistry, Environmental Chemistry, Pharmacology, Pharmacodynamics, Pharmacokinetics and Instrumental Chemistry. Toxicology is the study of the toxic substances which are poisons and their risky effects on biological systems. Drugs are medicines for diseases but can also have unsafe effects prominent to toxicity and deadly injuries

Occupational Toxicology Conferences | Toxicology Conferences | Pharmaceutical Conferences

11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; EUROTOX; Academy of Toxicological Sciences; American Board of Toxicology; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology

Track 5: Regulatory Toxicology

Regulatory Toxicology includes the gathering, handling and evaluation of epidemiological as well as experimental toxicology data to license toxicologically grounded results absorbed to the safety of health against injurious effects of biochemical materials. Furthermore, Regulatory Toxicology supports the growth of regular procedures and new challenging approaches in order to constantly progress the technical basis for decision-making developments.

Regulatory Toxicology Conferences | Toxicology Conferences | Pharmacovigilance Conference

12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Academy of Toxicological Sciences; Argentine Toxicological Association; American Board of Toxicology; EUROTOX; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Austrian Society of Toxicology; Colombia Society of Toxicology;

Track 6: Clinical Toxicology

Clinical toxicology is absorbed on the diseases related with short-term and long-term disclosure to numerous toxic substances. It typically overlaps with other disciplines such as biochemistry, pharmacology, and pathology. Persons who specify in clinical toxicology are referred to as clinical toxicologists. Their work emphases around the identification, analysis, and treatment of conditions resulting from disclosure to harmful agents. They regularly study the toxic effects of numerous drugs in the body, and are also apprehensive with the treatment and prevention of drug toxicity in the population.

Toxicology Conferences | Clinical Toxicology Conferences | Pharmacology Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States;Academy of Toxicological Sciences; American Board of Toxicology; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology;

Track 7: Computational Toxicology

Computational toxicology is a discipline in the area of computational molecular sciences which is definitely swiftly emerging due to the overall public attention stimulated by many of us initiatives. Health care specialists beauty sector fragrance and flavour as well seeing that lawmakers and chemical substance protection regulators. It really is of particular concern in remedy discovery and progression and its own assessment is compulsory for the getting of new medicines for humans make use of it. The effect of toxicity and safety connected events in the progression of new biochemical elements is significant whether it pertains to medications or other chemical substances.

Computational Conferences | Toxicology Conferences | Computational Toxicology Conferences

3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology; EUROTOX; Academy of Toxicological Sciences; American Board of Toxicology;

Track 8: Organ Toxicity

The gathering of antimicrobial drugs and their metabolic by-products in organs can be poisonous, leading to organ injury. Toxicity is the degree to which a material can harm an organism. Toxicity can mention to the effect on an entire organism and the result on a substructure of the creature such as organ which may effect on any organ of the human being organ or tissue in the human body can be affected by antimicrobial toxicity

Organ Toxicology Conferences | Toxicity Conferences | Neurotoxicology Conferences

3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; Predicting Drug Toxicity, June 13-14, 2017, Boston, USA 5th Immunogenicity & Immunotoxicity Conference ImmunoTX Summit on February 6-7, 2017 in San Diego, CA; 2nd International Conference on Pollutant Toxic Ions and Molecules, 6 - 9 November 2017, Lisbon, Portugal; 19th International Conference on Predictive Human Toxicity, February 16 - 17, 2017, London, United Kingdom; Stem Cells in Drug Discovery & Toxicity Screening, July 10-11, 2017, Boston, USA; American Board of Toxicology; Society of Toxicology ; Society of Toxicology of Canada; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology; EUROTOX; Academy of Toxicological Sciences;

Track 9: Applied Pharmacology

Applied Pharmacology is the clinical utilizations of the medications and its use in genuine medicinal practice. Where in this it lets the doctors to extend his realities of the medication the approach it would really work in the medicinal science. It is the utilization of the medications and how the pharmacological activities or data could be connected to the therapeutics. Additionally to give clarification to various medications having associated with the pharmacological activity. It Provides elucidations about medication collaborations and to clear up the activity of different medications on the numerous organs in the body when they are sick state with symptoms disagreements

Pharmacology Conferences | Toxicology Conferences | Pharmaceutical Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 5th International Conference on Pharmacology and Ethnopharmacology Mar 23-25, 2017 Orlando, USA; 6th Global Experts Meeting on Cardiovascular Pharmacology and Cardiac Medications April 13-14, 2017 Dubai, UAE; 7th Global Experts Meeting on Neuropharmacology July 31-Aug 02, 2017 Milan, Italy; 10th International Conference on Neuropharmacology and Neuropharmaceuticals Oct 23-24, 2017 Dubai, UAE; 7th European Congress of Pharmacology 26-30 June 2016 stanbul, Turkey; Annual International Conference on Pharmacology and Pharmaceutical Sciences (PHARMA), 26 - 27 October 2015 Bangkok, Thailand; 18th International Conference on Pharmaceutical Sciences and Pharmacology January 21-22,2016 Paris, France; 117th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics March 8 - 12, 2016 San Diego, California, USA; World congress on pharma and Advanced Clinical Research November 6-8, 2017, Singapore; American Board of Toxicology; Society of Toxicology ; Society of Toxicology of Canada; EUROTOX; Academy of Toxicological Sciences; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology

Track 10: Genetic Toxicology

Genetic toxicology is of the toxic effects of harm to deoxyribonucleic acid (DNA). Genetic info, programmed chemically in DNA, is conserved, simulated and transmitted to consecutive generations with high reliability. Damage to DNA can happen through usual biological procedure or as the result of contact of DNA, directly or indirectly, with biochemical, physical or agents. Genetic toxicology over the years has been to examine mechanisms of inheritance by providing tools to study DNA and RNA structure, DNA repair and the role of mutation at both the individual and population levels

Genetic Conferences | Medical Toxicology Conferences | Genetic Toxicology Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Society of Toxicology; Society of Toxicology of Canada; EUROTOX; Academy of Toxicological Sciences; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology; American Board of Toxicology

Track 11: Risk assessment

Risk assessment is a methodical investigation of an assignment, job or procedure that we carry out at work for the persistence of classifying the important risks that are present. Risk assessments are very significant as they form an essential part of a virtuous occupational health and safety management strategy. They help to make consciousness of exposures and risks. Identify them who may be at risk. The identification, assessment, and valuation of the levels of risks complicated in a situation, their assessment against standards, and determination of an acceptable level of risk

Risk Assessment Conferences | Occupational Conferences | Toxicology Conferences

11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Society of Toxicology; Society of Toxicology of Canada; EUROTOX; Academy of Toxicological Sciences; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology; American Board of Toxicology

Track 12: Environmental and Occupational Toxicology

Environmental Toxicology is the investigation of effects of contaminations on the structure and capacity of biological communities. It does exclude the regular poisons, additionally the synthetic chemicals and their impact on the earth. It relies on upon the impacts of the toxicants on the organic chemistry and physiology. The principle motivation behind the natural toxicology is to recognize the mode/site of the activity of a xenobiotic. It additionally incorporate how the chemicals travel through biological systems and how they are consumed and metabolized by plants and creatures, the instruments by which they cause illness, result in inherent deformities, or toxin living beings

Environmental Toxicology Conferences | Ecologic Conferences | Occupational Conferences

12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Academy of Toxicological Sciences; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Colombia Society of Toxicology; American Board of Toxicology; Society of Toxicology; Society of Toxicology of Canada

Track 13: Experimental Toxicology

Protection of any live non-human vertebrate drifting animals of a tame species shall not be used in processes. The take care of animals used in processes, including management, shall have had suitable education and preparation. Experimental Toxicology widely covers all features of experimental and clinical studies of functional, biochemical and structural disorder. Validity announcements are also given in valuation procedures particularly if a skilled must choose which data of.

Experimental Conferences | Toxicology Conferences | Pharmaceutical Conferences

10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA;9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; American College of Medical Toxicology; Argentine Toxicological Association; American Board of Toxicology; Society of Toxicology; Society of Toxicology of Canada

Track 14: Immunotoxicology

Immunotoxicology offers a critical assessment of planned experimental animal models and methods, and discusses the influence that immunotoxicity can make to the overall valuation of chemical-induced adverse health effects on individuals and the ecosystem. Animal models of autoimmunity associated with chemical exposure, includes recommendations for the selection of sentinel species in ecotoxicology

Immunological Conferences | Immunotoxicology Conferences | Toxicity Conferences

12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; 53rd European Societies of Toxicology, September 10-13, 2017, Bratislava, Slovak; 19th International Conference on Toxicology and Applied Pharmacology, March 29 - 30, 2017 Singapore, SG; 15th International Conference on Toxicology and Clinical Pharmacology December 14-16, 2017 Dubai, UAE; 56th Annual Meeting of Society of Toxicology March 12-16, 2017 Baltimore USA; Society of Environmental Toxicology and Chemistry North America 38th Annual Meeting, November 1216, 2017, Minneapolis, Minnesota, United States; Academy of Toxicological Sciences; International Union of Toxicology; American College of Medical Toxicology; Argentine Toxicological Association; Colombia Society of Toxicology; American Board of Toxicology; Society of Toxicology

Track 15: Toxicity Testing

Toxicity is key to evaluate potential dangers to people through the intense, sub endless, and interminable presentation of creatures to pesticides. The more correct sorts of harmfulness that are resolved incorporate cancer-causing nature; developing incorporating teratogenicity in regenerative danger and neurotoxicity the degree of metabolite testing required relies on upon the level of conceivable poisonous quality and ecological steadiness of the metabolite. A toxicity test, by augmentation, is intended to create information in regards to the antagonistic impacts of a material on human or creature wellbeing, or the earth.

Toxicology Conferences | Toxicity Conferences | Pharmaceutical Conferences

9th Euro-Global Summit on Toxicology and Applied Pharmacology June 22-24, 2017 Paris, France; 11th Global Toxicology and Risk Management Meeting October 10-12, 2017 London, UK; 10th Global Summit on Toxicology and Applied Pharmacology July 20-22, 2017 Chicago, USA; 3rd Global Genomics and Toxicogenomics Meeting September 27-28, 2017 Chicago, USA; 12th International Conference on Environmental Toxicology and Ecological Risk Assessment October 19-20, 2017 Atlanta, USA; Stem Cells in Drug Discovery & Toxicity Screening, July 10-11, 2017, Boston, USA; 2nd International Conference on Pollutant Toxic Ions and Molecules, 6 - 9 November 2017, Lisbon, Portugal; Predicting Drug Toxicity, June 13-14, 2017, Boston, USA 5th Immunogenicity & Immunotoxicity Conference, one of three parallel tracks to the ImmunoTX Summit on February 6-7, 2017 in San Diego, CA; 19th International Conference on Predictive Human Toxicity, February 16 - 17, 2017, London, United Kingdom; American Board of Toxicology; Society of Toxicology; Society of Toxicology of Canada; EUROTOX; Academy of Toxicological Sciences International Union of Toxicology; Argentine Toxicological Association; Austrian Society of Toxicology; Colombia Society of Toxicology; American College of Medical Toxicology

Toxicology 2016

6th Global Summit on Toxicology and Applied Pharmacology was hosted by the Conference Series LLC in Houston, USA during October 17-19, 2016. The conference was focused on the theme "Bringing together leading researchers to share pragmatic insights" and facilitated by the Conference Series LLC. Liberal reaction and cooperation was received from the Editorial Board Members of Conference Series LLC Journals, Toxicology-2016 Organizing Committee Members, and from researchers, analysts and pioneers in Toxicology.

The conference was started by the Keynote Forum and we are chuffed to thank all our Keynote Speakers, Honorable Guests, Speakers and Conference Attendees for creating a successful meeting.

The conference has encrusted through the following sessions:

We would like to specially mention our Keynote Speakers who participated very enthusiastically and actively

The speakers gave their productive commitment as exceptionally enlightening presentations and made the meeting an extraordinary achievement.

We thank all the members who supported the conference by encouraging the healthy discussions. Conference Series LLC expresses gratitude to the Organizing Committee Members for their generous nearness, support and help towards Toxicology-2016. After the immense idealistic reaction from logical crew, prestigious identities and the Editorial Board individuals from Conference Series LLC, we are pleased to announce our forth coming conference 10th Global Summit on Toxicology and Applied Pharmacology" to be held in Chicago, USA during July 20-22, 2017.

We anticipate your precious presence at the Toxicology-2017 Conference.

Let us meet again @ Toxicology-2017

Toxicology 2015

Toxicology 2015 Past Conference Report

Conference Series LLC is the proud host of the4thGlobal Summit on Toxicologywhich took place inPhiladelphia, USAduringAugust 24-26, 2015with the theme,Exploring the Tailored Strategies and Lucid Technologies in Toxicology and Pharmacology.The Editorial Board Members of Conference Series LLC Journals and the Organizing Committee Members of the conference have extended their unsparing support and active participation towards Toxicology 2015. The participants included eminent speakers, scientists, industrialists, delegates, researchers and students who thoroughly relished the conference.

The core of the conference revolved around interactive sessions on the following scientific tracks:

This event is a collaborative effort and Conference Series LLC would like to thank the following people for making this conference a grand success:

Moderators

Keynote Speakers

We would sincerely thank the distinguished speakers who resplendently conducted workshops on Genotoxicity:

The conference marked its start by an opening ceremony which included introduction by the Honorable Guests and the Members of Keynote Forum. All the speakers have extended their contribution in the form of highly informative presentations to lead the conference to the ladder of success. Conference Series LLC extends its warm gratitude towards all the Participants, Eminent Speakers, Young Researchers, Delegates and Students.

All accepted abstracts have been indexed inConference Series LLCjournal, theJournal ofClinical Toxicologyas a special issue.

After the huge optimistic response from scientific fraternity, renowned personalities and the Editorial Board Members ofConference Series LLCfrom across the world,Conference Series LLCis pleased to announce the5thGlobal Summit on Toxicology and Applied Pharmacologyto be held duringOctober 17-19, 2016inHouston, Texas, USA.

We look forward to welcoming you to theToxicology 2016Conference and hope that the event will be both informative and enjoyable.

Toxicology-2014

Toxicology 2014 Past Conference Report

The3rdInternational Summit on Toxicology & Applied Pharmacologytook place inChicago, USAonOctober 20-22, 2014. The conference was titled: New Challenges and Innovations in Pharmacological and Toxicological Sciences and hosted by theConference Series LLC. Generous response and active participation was received from the Editorial Board Members ofConference Series LLCJournals, Toxicology-2014 Organizing Committee Members, as well as from scientists, researchers and leaders in Toxicology.

Students from various parts of the world took active participation in poster presentations. Students who presented well were awarded Best Poster Presentations for their outstanding contribution in the field of Toxicology.

The conference was carried out through various sessions and the discussions were held on the following scientific tracks:

The conference was opened by introductions from the honorable guests and members of the keynote forum. On the first day of opening the keynote speakers were,

Gerhard Eisenbrand,University of Kaiserslautern, Germany

Pavel Vodicka,Institute of Experimental Medicine, Czech Republic

Anne Marie Vinggaard,Technical University of Denmark, Denmark

Special session was conducted by Carter Cliff, Cellular Dynamics International, USA on the topic Pluripotent stem cell models-Application in toxicology and beyond, Heres-Pulido M E, Universidad Nacional Autnoma de Mxico, Mexico on the topic The Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster.

Symposium conducted by Cinzia Forni from University of Rome Tor Vergata, Italy and Hemant Misra from Prolong Pharmaceuticals, USA and the title of the Symposium is Stress response in living organisms exposed to pollutants.

All the speakers gave their fruitful contribution in the form of highly informative presentations and made the conference a great success.

All accepted abstracts have been indexed inConference Series LLCJournal of Clinical Toxicologyas a special issue.

Toxicology-2013

Toxicology 2013 Past Conference Report

The2ndInternational Summit on Toxicologytook place inLas Vegas, USAonOctober 07-09, 2013.The conference was titled: Insight into the Global Issues of Toxicology and hosted by theConference Series LLC. Generous response and active participation was received from the Editorial Board Members ofConference Series LLCJournals, Organizing Committee Members, scientists, researchers, clinical experts and leaders from the field of Toxicology.

Original post:
Toxicology Conferences 2017 | Pharmacology Conferences ...

Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.

In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicine.

Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, mental retardation, autism, and mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics, teratogens, and prenatal diagnosis. Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for neurologic, endocrine, cardiovascular, pulmonary, ophthalmologic, renal, psychiatric, and dermatologic conditions.

In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, see the Human genome project) that have enabled an unprecedented understanding of genetic disorders.

Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders. Referrals are made to genetics clinics for a variety of reasons, including birth defects, developmental delay, autism, epilepsy, short stature, and many others. Examples of genetic syndromes that are commonly seen in the genetics clinic include chromosomal rearrangements, Down syndrome, DiGeorge syndrome (22q11.2 Deletion Syndrome), Fragile X syndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, and Williams syndrome.

In the United States, physicians who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG).[1] In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by the ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M.D. or D.O. degree (or their equivalent) and have completed a minimum of 24 months of training in an ACGME-accredited residency program in internal medicine, pediatrics, obstetrics and gynecology, or other medical specialty.[2]

Metabolic (or biochemical) genetics involves the diagnosis and management of inborn errors of metabolism in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates, amino acids, and lipids. Examples of metabolic disorders include galactosemia, glycogen storage disease, lysosomal storage disorders, metabolic acidosis, peroxisomal disorders, phenylketonuria, and urea cycle disorders.

Cytogenetics is the study of chromosomes and chromosome abnormalities. While cytogenetics historically relied on microscopy to analyze chromosomes, new molecular technologies such as array comparative genomic hybridization are now becoming widely used. Examples of chromosome abnormalities include aneuploidy, chromosomal rearrangements, and genomic deletion/duplication disorders.

Molecular genetics involves the discovery of and laboratory testing for DNA mutations that underlie many single gene disorders. Examples of single gene disorders include achondroplasia, cystic fibrosis, Duchenne muscular dystrophy, hereditary breast cancer (BRCA1/2), Huntington disease, Marfan syndrome, Noonan syndrome, and Rett syndrome. Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, and uniparental disomy.

Mitochondrial genetics concerns the diagnosis and management of mitochondrial disorders, which have a molecular basis but often result in biochemical abnormalities due to deficient energy production.

There exists some overlap between medical genetic diagnostic laboratories and molecular pathology.

Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, and risks in other family members, within the framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders. The precise role of the genetic counselor varies somewhat depending on the disorder.

Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism, brachydactyly (short fingers and toes), and hemophilia. Mathematical approaches were also devised and applied to human genetics. Population genetics was created.

Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in the 21st century.

The clinical setting in which patients are evaluated determines the scope of practice, diagnostic, and therapeutic interventions. For the purposes of general discussion, the typical encounters between patients and genetic practitioners may involve:

Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish a differential diagnosis and recommend appropriate testing. Increasingly, clinicians use SimulConsult, paired with the National Library of Medicine Gene Review articles, to narrow the list of hypotheses (known as the differential diagnosis) and identify the tests that are relevant for a particular patient. These tests might evaluate for chromosomal disorders, inborn errors of metabolism, or single gene disorders.

Chromosome studies are used in the general genetics clinic to determine a cause for developmental delay/mental retardation, birth defects, dysmorphic features, and/or autism. Chromosome analysis is also performed in the prenatal setting to determine whether a fetus is affected with aneuploidy or other chromosome rearrangements. Finally, chromosome abnormalities are often detected in cancer samples. A large number of different methods have been developed for chromosome analysis:

Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In the US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests:

Each cell of the body contains the hereditary information (DNA) wrapped up in structures called chromosomes. Since genetic syndromes are typically the result of alterations of the chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly inborn errors of metabolism, the mechanism of disease is well understood and offers the potential for dietary and medical management to prevent or reduce the long-term complications. In other cases, infusion therapy is used to replace the missing enzyme. Current research is actively seeking to use gene therapy or other new medications to treat specific genetic disorders.

In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in the hypothetical example:

Compound "A" is metabolized to "B" by enzyme "X", compound "B" is metabolized to "C" by enzyme "Y", and compound "C" is metabolized to "D" by enzyme "Z". If enzyme "Z" is missing, compound "D" will be missing, while compounds "A", "B", and "C" will build up. The pathogenesis of this particular condition could result from lack of compound "D", if it is critical for some cellular function, or from toxicity due to excess "A", "B", and/or "C". Treatment of the metabolic disorder could be achieved through dietary supplementation of compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with a medication that promoted disposal of excess "A", "B", or "C". Another approach that can be taken is enzyme replacement therapy, in which a patient is given an infusion of the missing enzyme.

Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including galactosemia, phenylketonuria (PKU), maple syrup urine disease, organic acidurias and urea cycle disorders. Such restrictive diets can be difficult for the patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders.

Medical approaches include enhancement of residual enzyme activity (in cases where the enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase, treatment with NTBC in Tyrosinemia to inhibit the production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders.

Certain lysosomal storage diseases are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include Gaucher disease, Fabry disease, Mucopolysaccharidoses and Glycogen storage disease type II. Such treatments are limited by the ability of the enzyme to reach the affected areas (the blood brain barrier prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders.

There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. It should be noted that the information included in this section applies to the typical pathways in the United States and there may be differences in other countries. US Practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics.

Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different from a typically laboratory test that provides a "snapshot" of an individual's health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns.

On 19 March 2015, scientists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger, to edit the human genome in a way that can be inherited.[3][4][5][6] In April 2015 and April 2016, Chinese researchers reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[7][8][9] In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR and related techniques on condition that the embryos were destroyed within seven days.[10] In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit.[11]

The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the American Society of Human Genetics. The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis.

Medical genetics is now recognized as a distinct medical specialty in the U.S. with its own approved board (the American Board of Medical Genetics) and clinical specialty college (the American College of Medical Genetics). The College holds an annual scientific meeting, publishes a monthly journal, Genetics in Medicine, and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics.

The broad range of research in medical genetics reflects the overall scope of this field, including basic research on genetic inheritance and the human genome, mechanisms of genetic and metabolic disorders, translational research on new treatment modalities, and the impact of genetic testing

Basic research geneticists usually undertake research in universities, biotechnology firms and research institutes.

Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation influence group differences in health outcomes.[12][13][14] According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases.[15] Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model.[16] However, the generality of the model has not yet been established and, in some cases, is in doubt.[13][17][18] Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model.[19]

Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare.[20][21] Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry.[19][22] However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in the incidence of the disease.

The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background.[17][23][24][25] If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift.[26]

One area in which population categories can be important considerations in genetics research is in controlling for confounding between population substructure, environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied,[27] although the magnitude of this problem in genetic association studies is subject to debate.[28][29] Various methods have been developed to detect and account for population substructure,[30][31] but these methods can be difficult to apply in practice.[32]

Population substructure also can be used to advantage in genetic association studies. For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations.[33][34][35][36] Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.[37][38]

Go here to see the original:
Medical genetics - Wikipedia

The genetic code is the set of rules by which information encoded within genetic material (DNA or mRNA sequences) is translated into proteins by living cells. Translation is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

The code defines how sequences of nucleotide triplets, called codons, specify which amino acid will be added next during protein synthesis. With some exceptions,[1] a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. Because the vast majority of genes are encoded with exactly the same code (see the RNA codon table), this particular code is often referred to as the canonical or standard genetic code, or simply the genetic code, though in fact some variant codes have evolved. For example, protein synthesis in human mitochondria relies on a genetic code that differs from the standard genetic code.

While the "genetic code" determines a protein's amino acid sequence, other genomic regions determine when and where these proteins are produced according to a multitude of more complex "gene regulatory codes".

Serious efforts to understand how proteins are encoded began after the structure of DNA was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins. With four different nucleotides, a code of 2 nucleotides would allow for only a maximum of 42 = 16 amino acids. A code of 3 nucleotides could code for a maximum of 43 = 64 amino acids.[2]

The Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases; Marshall Nirenberg and Heinrich J. Matthaei were the first to elucidate the nature of a codon in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine.[3] They thereby deduced that the codon UUU specified the amino acid phenylalanine. This was followed by experiments in Severo Ochoa's laboratory that demonstrated that the poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysine[4] and that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline.[5] Therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using different copolymers most of the remaining codons were then determined. Subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA (tRNA), the adapter molecule that facilitates the process of translating RNA into protein. This work was based upon earlier studies by Severo Ochoa, who received the Nobel Prize in Physiology or Medicine in 1959 for his work on the enzymology of RNA synthesis.[6]

Extending this work, Nirenberg and Philip Leder revealed the triplet nature of the genetic code and deciphered the codons of the standard genetic code. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, the components of cells that translate RNA into protein. Unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments.[7] In 1968, Khorana, Holley and Nirenberg received the Nobel Prize in Physiology or Medicine for their work.[8]

A codon is defined by the initial nucleotide from which translation starts and sets the frame for a run of uninterrupted triplets, which is known as an "open reading frame" (ORF). For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA, and CCC; and, if read from the second position, it contains the codons GGA and AAC; if read starting from the third position, GAA and ACC. Every sequence can, thus, be read in its 5' 3' direction in three reading frames, each of which will produce a different amino acid sequence (in the given example, Gly-Lys-Pro, Gly-Asn, or Glu-Thr, respectively). With double-stranded DNA, there are six possible reading frames, three in the forward orientation on one strand and three reverse on the opposite strand.[9]:330 The actual frame from which a protein sequence is translated is defined by a start codon, usually the first AUG codon in the mRNA sequence.

In eukaryotes, ORFs in exons are often interrupted by introns.

Translation starts with a chain initiation codon or start codon. Unlike stop codons, the codon alone is not sufficient to begin the process. Nearby sequences such as the Shine-Dalgarno sequence in E. coli and initiation factors are also required to start translation. The most common start codon is AUG, which is read as methionine or, in bacteria, as formylmethionine. Alternative start codons depending on the organism include "GUG" or "UUG"; these codons normally represent valine and leucine, respectively, but as start codons they are translated as methionine or formylmethionine.[10]

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. "Amber" was named by discoverers Richard Epstein and Charles Steinberg after their friend Harris Bernstein, whose last name means "amber" in German.[11] The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme. Stop codons are also called "termination" or "nonsense" codons. They signal release of the nascent polypeptide from the ribosome because there is no cognate tRNA that has anticodons complementary to these stop signals, and so a release factor binds to the ribosome instead.[12]

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can affect the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low1 error in every 10100million basesdue to the "proofreading" ability of DNA polymerases.[14][15]

Missense mutations and nonsense mutations are examples of point mutations, which can cause genetic diseases such as sickle-cell disease and thalassemia respectively.[16][17][18] Clinically important missense mutations generally change the properties of the coded amino acid residue between being basic, acidic, polar or non-polar, whereas nonsense mutations result in a stop codon.[9]:266

Mutations that disrupt the reading frame sequence by indels (insertions or deletions) of a non-multiple of 3 nucleotide bases are known as frameshift mutations. These mutations usually result in a completely different translation from the original, and are also very likely to cause a stop codon to be read, which truncates the creation of the protein.[19] These mutations may impair the function of the resulting protein, and are thus rare in in vivo protein-coding sequences. One reason inheritance of frameshift mutations is rare is that, if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause death before the organism is viable.[20] Frameshift mutations may result in severe genetic diseases such as Tay-Sachs disease.[21]

Although most mutations that change protein sequences are harmful or neutral, some mutations have a beneficial effect on an organism.[22] These mutations may enable the mutant organism to withstand particular environmental stresses better than wild type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection.[23]Viruses that use RNA as their genetic material have rapid mutation rates,[24] which can be an advantage, since these viruses will evolve constantly and rapidly, and thus evade the defensive responses of e.g. the human immune system.[25] In large populations of asexually reproducing organisms, for example, E. coli, multiple beneficial mutations may co-occur. This phenomenon is called clonal interference and causes competition among the mutations.[26]

Degeneracy is the redundancy of the genetic code. This term was given by Bernfield and Nirenberg. The genetic code has redundancy but no ambiguity (see the codon tables below for the full correlation). For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example, the amino acid leucine is specified by YUR or CUN (UUA, UUG, CUU, CUC, CUA, or CUG) codons (difference in the first or third position indicated using IUPAC notation), while the amino acid serine is specified by UCN or AGY (UCA, UCG, UCC, UCU, AGU, or AGC) codons (difference in the first, second, or third position).[27]:102117:521522 A practical consequence of redundancy is that errors in the third position of the triplet codon cause only a silent mutation or an error that would not affect the protein because the hydrophilicity or hydrophobicity is maintained by equivalent substitution of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids. NCN yields amino acid residues that are small in size and moderate in hydropathy; NAN encodes average size hydrophilic residues. The genetic code is so well-structured for hydropathy that a mathematical analysis (Singular Value Decomposition) of 12 variables (4 nucleotides x 3 positions) yields a remarkable correlation (C = 0.95) for predicting the hydropathy of the encoded amino acid directly from the triplet nucleotide sequence, without translation.[28][29] Note in the table, below, eight amino acids are not affected at all by mutations at the third position of the codon, whereas in the figure above, a mutation at the second position is likely to cause a radical change in the physicochemical properties of the encoded amino acid.

The frequency of codons, also known as codon usage bias, can vary from species to species with functional implications for the control of translation. The following codon usage table is for the human genome.[30]

While slight variations on the standard code had been predicted earlier,[31] none were discovered until 1979, when researchers studying human mitochondrial genes discovered they used an alternative code.[32] Many slight variants have been discovered since then,[33] including various alternative mitochondrial codes,[34] and small variants such as translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than a leucine in yeasts of the "CTG clade" (Candida albicans is member of this group).[35][36][37] Because viruses must use the same genetic code as their hosts, modifications to the standard genetic code could interfere with the synthesis or functioning of viral proteins.[38] However, some viruses (such as totiviruses) have adapted to the genetic code modification of the host.[39] In bacteria and archaea, GUG and UUG are common start codons, but in rare cases, certain proteins may use alternative start codons not normally used by that species.[33]

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending on associated signal sequences in the messenger RNA. For example, UGA can code for selenocysteine and UAG can code for pyrrolysine. Selenocysteine is now viewed as the 21st amino acid, and pyrrolysine is viewed as the 22nd.[33] Unlike selenocysteine, pyrrolysine encoded UAG is translated with the participation of a dedicated aminoacyl-tRNA synthetase.[40] Both selenocysteine and pyrrolysine may be present in the same organism.[41] Although the genetic code is normally fixed in an organism, the achaeal prokaryote Acetohalobium arabaticum can expand its genetic code from 20 to 21 amino acids (by including pyrrolysine) under different conditions of growth.[42]

Despite these differences, all known naturally occurring codes are very similar to each other, and the coding mechanism is the same for all organisms: three-base codons, tRNA, ribosomes, reading the code in the same direction and translating the code three letters at a time into sequences of amino acids.

Variant genetic codes used by an organism can be inferred by identifying highly conserved genes encoded in that genome, and comparing its codon usage to the amino acids in homologous proteins of other organisms. For example, the program FACIL[43] infers a genetic code by searching which amino acids in homologous protein domains are most often aligned to every codon. The resulting amino acid probabilities for each codon are displayed in a genetic code logo, that also shows the support for a stop codon.

The DNA codon table is essentially identical to that for RNA, but with U replaced by T.

The origin of the genetic code is a part of the question of the origin of life. Under the main hypothesis for the origin of life, the RNA world hypothesis, any model for the emergence of genetic code is intimately related to a model of the transfer from ribozymes (RNA enzymes) to proteins as the principal enzymes in cells. In line with the RNA world hypothesis, transfer RNA molecules appear to have evolved before modern aminoacyl-tRNA synthetases, so the latter cannot be part of the explanation of its patterns.[45]

A consideration of a hypothetical random genetic code further motivates a biochemical or evolutionary model for the origin of the genetic code. If amino acids were randomly assigned to triplet codons, there would be 1.51084 possible genetic codes to choose from.[46]:163 This number is found by calculating how many ways there are to place 21 items (20 amino acids plus one stop) in 64 bins, wherein each item is used at least once. [2] In fact, the distribution of codon assignments in the genetic code is nonrandom.[47] In particular, the genetic code clusters certain amino acid assignments. For example, amino acids that share the same biosynthetic pathway tend to have the same first base in their codons. This could be an evolutionary relic of early simpler genetic code with fewer amino acids, that later diverged to code for a larger set of amino acids.[48] It could also reflect steric and chemical properties that had another effect on the codon during its evolution. Amino acids with similar physical properties also tend to have similar codons,[49][50] reducing the problems caused by point mutations and mistranslations.[47]

Given the non-random genetic triplet coding scheme, it has been suggested that a tenable hypothesis for the origin of genetic code should address multiple aspects of the codon table such as absence of codons for D-amino acids, secondary codon patterns for some amino acids, confinement of synonymous positions to third position, a limited set of only 20 amino acids instead of a number closer to 64, and the relation of stop codon patterns to amino acid coding patterns.[51]

There are three main ideas for the origin of the genetic code, and many models belong to either one of them or to a combination thereof:[52]

Hypotheses for the origin of the genetic code have addressed a variety of scenarios:[56]

Since 2001, 40 non-natural amino acids have been added into protein by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl tRNA-synthetase pair to encode it with diverse physicochemical and biological properties in order to be used as a tool to exploring protein structure and function or to create novel or enhanced proteins.[71][72]

H. Murakami and M. Sisido have extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th (in vivo) codon.[73]

Read this article:
Genetic code - Wikipedia

The Master of Science in Genetic Counseling Program at the Icahn School of Medicine at Mount Sinai (ISMMS) provides students with many opportunities for study, research, and practice in the challenging and exciting field of genetic counseling.

Our program, part of the ISMMS Graduate School of Biomedical Sciences, is sponsored by the Department of Genetics and Genomics Sciences, one of the largest departments of its kind in the world. Our faculty is renowned in the diagnosis, treatment and counseling of genetic disorders and is at the forefront of basic science research. Our large multidisciplinary center provides clinical and laboratory services to a wide range of culturally diverse patients and their families, along with our proven commitment to the community we serve.

The Master of Science in Genetic Counseling program is a 21-month, full-time course of study accredited by the Accreditation Council for Genetic Counseling (ACGC), which blends didactic coursework with a variety of clinical rotations.The Program has a 100% job placement rate for those seeking positions within the genetic counseling field. The first time Board certification pass rate for the classes of 2013, 2014 and 2015 is 95.5%.

Our students grow in skills and knowledge while enjoying access to the incomparable opportunities present in a prestigious academic medical center in the heart of New York City.

The Genetic Counseling Program was established in 1991 as a Certificate Program to train individuals with related advanced degrees to become genetic counselors. It became a Master of Science degree program in 1995 and is accredited by the Accreditation Council for Genetic Counseling (ACGC). As part of The Mount Sinai Health System.Our students have access to the laboratories, libraries, and educational resources of ISMMS as part of The Mount Sinai Health System.

The integration of academic and clinical disciplines within one of the country's preeminent health systems provides an ideal environment for our master's program, affording our students unparalleled opportunities for study, research, and practice in the challenging and exciting field of genetic counseling.

Randi Zinberg, MS, CGC Director, Master of Science Program in Genetic Counseling Email: randi.zinberg@mssm.edu

Sabrina Suckiel, MS, CGC Assistant Director, Master of Science Program in Genetic Counseling Email: sabrina.suckiel@mssm.edu

Julie McGlynn, MS, CGC Director, Clinical Training, Master of Science Program in Genetic Counseling Email: julie.mcglynn@mssm.edu

Genetics and Genomics Faculty

Who are genetic counselors?

Integrating the digital universe to better diagnose, treat and prevent disease

A professional network for the interests of genetic counselors

Promoting high standards in genetic counseling

Student Life and Resources

1st Year Genetic Counseling Program Experience at ISMMS

Live in one of the worlds most vibrant cities

Finance your graduate education

Course registrations, academic calendars, transcripts and more

Embracing the principles of diversity and inclusion

Learn about graduate student housing

Discover and explore research at ISMMS

Read the original:
Master of Science in Genetic Counseling | Icahn School of ...

Bookshelf

A collection of biomedical books that can be searched directly or from linked data in other NCBI databases. The collection includes biomedical textbooks, other scientific titles, genetic resources such as GeneReviews, and NCBI help manuals.

A resource to provide a public, tracked record of reported relationships between human variation and observed health status with supporting evidence. Related information intheNIH Genetic Testing Registry (GTR),MedGen,Gene,OMIM,PubMedand other sources is accessible through hyperlinks on the records.

A registry and results database of publicly- and privately-supported clinical studies of human participants conducted around the world.

An archive and distribution center for the description and results of studies which investigate the interaction of genotype and phenotype. These studies include genome-wide association (GWAS), medical resequencing, molecular diagnostic assays, as well as association between genotype and non-clinical traits.

An open, publicly accessible platform where the HLA community can submit, edit, view, and exchange data related to the human major histocompatibility complex. It consists of an interactive Alignment Viewer for HLA and related genes, an MHC microsatellite database, a sequence interpretation site for Sequencing Based Typing (SBT), and a Primer/Probe database.

A searchable database of genes, focusing on genomes that have been completely sequenced and that have an active research community to contribute gene-specific data. Information includes nomenclature, chromosomal localization, gene products and their attributes (e.g., protein interactions), associated markers, phenotypes, interactions, and links to citations, sequences, variation details, maps, expression reports, homologs, protein domain content, and external databases.

A collection of expert-authored, peer-reviewed disease descriptions on the NCBI Bookshelf that apply genetic testing to the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions.

Summaries of information for selected genetic disorders with discussions of the underlying mutation(s) and clinical features, as well as links to related databases and organizations.

A voluntary registry of genetic tests and laboratories, with detailed information about the tests such as what is measured and analytic and clinical validity. GTR also is a nexus for information about genetic conditions and provides context-specific links to a variety of resources, including practice guidelines, published literature, and genetic data/information. The initial scope of GTR includes single gene tests for Mendelian disorders, as well as arrays, panels and pharmacogenetic tests.

A database of known interactions of HIV-1 proteins with proteins from human hosts. It provides annotated bibliographies of published reports of protein interactions, with links to the corresponding PubMed records and sequence data.

A compilation of data from the NIAID Influenza Genome Sequencing Project and GenBank. It provides tools for flu sequence analysis, annotation and submission to GenBank. This resource also has links to other flu sequence resources, and publications and general information about flu viruses.

A portal to information about medical genetics. MedGen includes term lists from multiple sources and organizes them into concept groupings and hierarchies. Links are also provided to information related to those concepts in the NIH Genetic Testing Registry (GTR), ClinVar,Gene, OMIM, PubMed, and other sources.

A project involving the collection and analysis of bacterial pathogen genomic sequences originating from food, environmental and patient isolates. Currently, an automated pipeline clusters and identifies sequences supplied primarily by public health laboratories to assist in the investigation of foodborne disease outbreaks and discover potential sources of food contamination.

A database of human genes and genetic disorders. NCBI maintains current content and continues to support its searching and integration with other NCBI databases. However, OMIM now has a new home at omim.org, and users are directed to this site for full record displays.

A database of citations and abstracts for biomedical literature from MEDLINE and additional life science journals. Links are provided when full text versions of the articles are available via PubMed Central (described below) or other websites.

A digital archive of full-text biomedical and life sciences journal literature, including clinical medicine and public health.

A collection of clinical effectiveness reviews and other resources to help consumers and clinicians use and understand clinical research results. These are drawn from the NCBI Bookshelf and PubMed, including published systematic reviews from organizations such as the Agency for Health Care Research and Quality, The Cochrane Collaboration, and others (see complete listing). Links to full text articles are provided when available.

A collection of resources specifically designed to support the research of retroviruses, including a genotyping tool that uses the BLAST algorithm to identify the genotype of a query sequence; an alignment tool for global alignment of multiple sequences; an HIV-1 automatic sequence annotation tool; and annotated maps of numerous retroviruses viewable in GenBank, FASTA, and graphic formats, with links to associated sequence records.

A summary of data for the SARS coronavirus (CoV), including links to the most recent sequence data and publications, links to other SARS related resources, and a pre-computed alignment of genome sequences from various isolates.

An extension of the Influenza Virus Resource to other organisms, providing an interface to download sequence sets of selected viruses, analysis tools, including virus-specific BLAST pages, and genome annotation pipelines.

Read more:
Genetics & Medicine - Site Guide - NCBI

Deoxyribonucleic acid (i;[1]DNA) is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), they are one of the four major types of macromolecules that are essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix.

The two DNA strands are termed polynucleotides since they are composed of simpler monomer units called nucleotides.[2][3] Each nucleotide is composed of one of four nitrogen-containing nucleobaseseither cytosine (C), guanine (G), adenine (A), or thymine (T)and a sugar called deoxyribose and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together (according to base pairing rules (A with T, and C with G) with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, and weighs 50 billion tonnes.[4] In comparison, the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon (TtC).[5]

DNA stores biological information. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences.

The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts.[6] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was identified by James Watson and Francis Crick in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.[7]

DNA is a long polymer made from repeating units called nucleotides.[8][9] The structure of DNA is non-static,[10] all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34ngstrms (3.4nanometres) and a radius of 10ngstrms (1.0nanometre).[11] According to another study, when measured in a particular solution, the DNA chain measured 22 to 26ngstrms wide (2.2 to 2.6nanometres), and one nucleotide unit measured 3.3 (0.33nm) long.[12] Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the DNA in the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs[13] and would be 85mm long if straightened.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.[14][15] These two long strands entwine like vines, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.[16]

The backbone of the DNA strand is made from alternating phosphate and sugar residues.[17] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime (5) and three prime (3), with the 5 end having a terminal phosphate group and the 3 end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.[15]

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.[19] In the aqueous environment of the cell, the conjugated bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.[20][21]

The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T.[15] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.[22]

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37, thymine has been replaced by uracil.[23] Another phage - Staphylococcal phage S6 - has been identified with a genome where thymine has been replaced by uracil.[24]

Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera.[25] Biosynthesis of J occurs in two steps: in the first step a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second HOMedU is glycosylated to form J.[26] Proteins that bind specifically to this base have been identified.[27][28][29] These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia.[30] J appears to act as a termination signal for RNA polymerase II.[31][32]

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 wide and the other, the minor groove, is 12 wide.[33] The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.[34] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.[35] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[9]

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart a process known as melting to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands.[36] In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.[37]

In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.[38]

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[39] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.[40] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.[41]

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.[42] In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,[43] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.[44]

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.[45] If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.[46] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[47]

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.[17] The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.[48]

The first published reports of A-DNA X-ray diffraction patternsand also B-DNAused analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA.[49][50] An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions.[51] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.[11]

Although the B-DNA form is most common under the conditions found in cells,[52] it is not a well-defined conformation but a family of related DNA conformations[53] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.[54][55]

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.[56][57] Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.[58] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.[59]

For many years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced,[60][60][61] though the research was disputed,[61][62] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.[63]

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3 ends of chromosomes.[64] These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.[65] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.[66]

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure.[68] These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit.[69] Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.[70] At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.[68]

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.[71] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.[72]

For one example, cytosine methylation, produces 5-methylcytosine, which is important for X-inactivation of chromosomes.[73] The average level of methylation varies between organisms the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.[74] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.[75] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,[76] and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[77][78]

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.[80] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.[81] A typical human cell contains about 150,000 bases that have suffered oxidative damage.[82] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.[83] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[84][85] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.[86][87][88]

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.[89] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.[90] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.[91] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.[92]

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[93] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.[94] The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.[95] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma".[96] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.[97]

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes.[65][99] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.[100] These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.[101]

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5 to 3 direction, different mechanisms are used to copy the antiparallel strands of the double helix.[102] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 g/L, and its concentration in natural aquatic environments may be as high at 88 g/L.[103] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;[104] it may provide nutrients;[105] and it may act as a buffer to recruit or titrate ions or antibiotics.[106] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;[107] it may contribute to biofilm formation;[108] and it may contribute to the biofilm's physical strength and resistance to biological stress.[109]

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[110][111] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.[112] Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[113] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[114] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.[115] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.[116]

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[117] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[119] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.[120]

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[121] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[34]

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5-GATATC-3 and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system.[123] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands.[124] Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.[124]

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.[46] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.[125] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.[47]

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.[126] These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are created based on existing polynucleotide chainswhich are called templates. These enzymes function by repeatedly adding a nucleotide to the 3 hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5 to 3 direction.[127] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3 to 5 exonuclease activity is activated and the incorrect base removed.[128] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.[129]

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.[64][130] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.[65]

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.[131]

A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[133] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.[134] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.[135]

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.[136] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.[137] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.[138]

DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.[139][140] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.[141] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.[142] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.[143] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,[144] but these claims are controversial.[145][146]

Building blocks of DNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.[147][148][149] Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.[150]

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.[151] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[152] or be grown in agriculture.[153][154]

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.[155] However, identification can be complicated if the scene is contaminated with DNA from several people.[156] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,[157] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[158]

The development of forensic science, and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defence to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also used successfully to positively identify victims of mass casualty incidents,[159] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth but there are new methods to test paternity while a mother is still pregnant.[160]

Deoxyribozymes, also called DNAzymes or catalytic DNA are first discovered in 1994.[161] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.[162] The most extensively studied class of DNAzymes are RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),[161] the CA1-3 DNAzymes (copper-specific),[163] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).[164] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in living cells.

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory.[165] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.[166] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function.[167] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.[168] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.[169] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.[170]Nanomechanical devices and algorithmic self-assembly have also been demonstrated,[171] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.[172]

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.[173] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[174][175]

In a paper published in Nature in January 2013, scientists from the European Bioinformatics Institute and Agilent Technologies proposed a mechanism to use DNA's ability to code information as a means of digital data storage. The group was able to encode 739 kilobytes of data into DNA code, synthesize the actual DNA, then sequence the DNA and decode the information back to its original form, with a reported 100% accuracy. The encoded information consisted of text files and audio files. A prior experiment was published in August 2012. It was conducted by researchers at Harvard University, where the text of a 54,000-word book was encoded in DNA.[176][177]

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".[178][179] In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.[180][181] In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit.[182] Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. Levene thought the chain was short and the bases repeated in a fixed order. In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.[183]

In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".[184][185] In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.[186][187] This system provided the first clear suggestion that DNA carries genetic informationthe AveryMacLeodMcCarty experimentwhen Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943.[188] DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the HersheyChase experiment showed that DNA is the genetic material of the T2 phage.[189]

In 1953, James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature.[11] Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51")[190] taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired.

Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.[191] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model;[50][192] this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature.[51] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.[193] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.[194]

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[195] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the MeselsonStahl experiment.[196] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.[197] These findings represent the birth of molecular biology.

Read more from the original source:
DNA - Wikipedia

What are BRCA1 and BRCA2?

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of the cells genetic material. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast and ovarian cancers, and they have been associated with increased risks of several additional types of cancer. Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers (1) and about 5 to 10 percent of all breast cancers (2). In addition, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall (3). Breast and ovarian cancers associated with BRCA1 and BRCA2 mutations tend to develop at younger ages than their nonhereditary counterparts.

A harmful BRCA1 or BRCA2 mutation can be inherited from a persons mother or father. Each child of a parent who carries a mutation in one of these genes has a 50 percent chance (or 1 chance in 2) of inheriting the mutation. The effects of mutations in BRCA1 and BRCA2 are seen even when a persons second copy of the gene is normal.

How much does having a BRCA1 or BRCA2 gene mutation increase a womans risk of breast and ovarian cancer?

A womans lifetime risk of developing breast and/or ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2.

Breast cancer: About 12 percent of women in the general population will develop breast cancer sometime during their lives (4). By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years (5, 6).

Ovarian cancer: About 1.3 percent of women in the general population will develop ovarian cancer sometime during their lives (4). By contrast, according to the most recent estimates, 39 percent of women who inherit a harmful BRCA1 mutation (5, 6) and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years (5, 6).

It is important to note that these estimated percentages of lifetime risk are different from those available previously; the estimates have changed as more information has become available, and they may change again with additional research. No long-term general population studies have directly compared cancer risk in women who have and do not have a harmful BRCA1 or BRCA2 mutation.

It is also important to note that other characteristics of a particular woman can make her cancer risk higher or lower than the average risks. These characteristics include her family history ofbreast, ovarian, and, possibly, other cancers; the specific mutation(s) she has inherited; and other risk factors, suchas her reproductivehistory. However, at this time, based on current data, none of these other factors seems to be as strong as the effect of carrying a harmful BRCA1 or BRCA2 mutation.

What other cancers have been linked to mutations in BRCA1 and BRCA2?

Are mutations in BRCA1 and BRCA2 more common in certain racial/ethnic populations than others?

Yes. For example, people of Ashkenazi Jewish descent have a higher prevalence of harmful BRCA1 and BRCA2 mutations than people in the general U.S. population. Other ethnic and geographic populations around the world, such as the Norwegian, Dutch, and Icelandic peoples, also have a higher prevalence of specific harmful BRCA1 and BRCA2 mutations.

In addition, limited data indicate that the prevalence of specific harmful BRCA1 and BRCA2 mutations may vary among individual racial and ethnic groups in the United States, including African Americans, Hispanics, Asian Americans, and non-Hispanic whites (15, 16).

Are genetic tests available to detect BRCA1 and BRCA2 mutations?

Yes. Several different tests are available, including tests that look for a known mutation in one of the genes (i.e., a mutation that has already been identified in another family member) and tests that check for all possible mutations in both genes. DNA (from a blood or saliva sample) is needed for mutation testing. The sample is sent to a laboratory for analysis. It usually takes about a month to get the test results.

Who should consider genetic testing for BRCA1 and BRCA2 mutations?

Because harmful BRCA1 and BRCA2 gene mutations are relatively rare in the general population, most experts agree that mutation testing of individuals who do not have cancer should be performed only when the persons individual or family history suggests the possible presence of a harmful mutation in BRCA1 or BRCA2.

In December 2013, the United States Preventive Services Task Force recommended that women who have family members with breast, ovarian, fallopian tube, or peritoneal cancer be evaluated to see if they have a family history that is associated with an increased risk of a harmful mutation in one of these genes (17).

Several screening tools are now available to help health care providers with this evaluation (17). These tools assess family history factors that are associated with an increased likelihood of having a harmful mutation in BRCA1 or BRCA2, including:

When an individual has a family history that is suggestive of the presence of a BRCA1 or BRCA2 mutation, it may be most informative to first test a family member who has cancer if that person is still alive and willing to be tested. If that person is found to have a harmful BRCA1 or BRCA2 mutation, then other family members may want to consider genetic counseling to learn more about their potential risks and whether genetic testing for mutations in BRCA1 and BRCA2 might be appropriate for them.

If it is not possible to confirm the presence of a harmful BRCA1 or BRCA2 mutation in a family member who has cancer, it is appropriate for both men and women who do not have cancer but have a family medical history that suggests the presence of such a mutation to have genetic counseling for possible testing.

Some individualsfor example, those who were adopted at birthmay not know their family history. In cases where a woman with an unknown family history has an early-onset breast cancer or ovarian cancer or a man with an unknown family history is diagnosed with breast cancer, it may be reasonable for that individual to consider genetic testing for a BRCA1 or BRCA2 mutation. Individuals with an unknown family history who do not have an early-onset cancer or male breast cancer are at very low risk of having a harmful BRCA1 or BRCA2 mutation and are unlikely to benefit from routine genetic testing.

Professional societies do not recommend that children, even those with a family history suggestive of a harmful BRCA1 or BRCA2 mutation, undergo genetic testing for BRCA1 or BRCA2. This is because no risk-reduction strategies exist for children, and children's risks of developing a cancer type associated with a BRCA1 or BRCA2 mutation are extremely low. After children with a family history suggestive of a harmful BRCA1 or BRCA2 mutation become adults, however, they may want to obtain genetic counseling about whether or not to undergoing genetic testing.

Should people considering genetic testing for BRCA1 and BRCA2 mutations talk with a genetic counselor?

Genetic counseling is generally recommended before and after any genetic test for an inherited cancer syndrome. This counseling should be performed by a health care professional who is experienced in cancer genetics. Genetic counseling usually covers many aspects of the testing process, including:

How much does BRCA1 and BRCA2 mutation testing cost?

The Affordable Care Act considers genetic counseling and BRCA1 and BRCA2 mutation testing for individuals at high risk a covered preventive service. People considering BRCA1 and BRCA2 mutation testing may want to confirm their insurance coverage for genetic tests before having the test.

Some of the genetic testing companies that offer testing for BRCA1 and BRCA2 mutations may offer testing at no charge to patients who lack insurance and meet specific financial and medical criteria.

What does a positive BRCA1 or BRCA2 genetic test result mean?

BRCA1 and BRCA2 gene mutation testing can give several possible results: a positive result, a negative result, or an ambiguous or uncertain result.

A positive test result indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 and, therefore, has an increased risk of developing certain cancers. However, a positive test result cannot tell whether or when an individual will actually develop cancer. For example, some women who inherit a harmful BRCA1 or BRCA2 mutation will never develop breast or ovarian cancer.

A positive genetic test result may also have important health and social implications for family members, including future generations. Unlike most other medical tests, genetic tests can reveal information not only about the person being tested but also about that persons relatives:

What does a negative BRCA1 or BRCA2 test result mean?

A negative test result can be more difficult to understand than a positive result because what the result means depends in part on an individuals family history of cancer and whether a BRCA1 or BRCA2 mutation has been identified in a blood relative.

If a close (first- or second-degree) relative of the tested person is known to carry a harmful BRCA1 or BRCA2 mutation, a negative test result is clear: it means that person does not carry the harmful mutation that is responsible for the familial cancer, and thus cannot pass it on to their children. Such a test result is called a true negative. A person with such a test result is currently thought to have the same risk of cancer as someone in the general population.

If the tested person has a family history that suggests the possibility of having a harmful mutation in BRCA1 or BRCA2 but complete gene testing identifies no such mutation in the family, a negative result is less clear. The likelihood that genetic testing will miss a known harmful BRCA1 or BRCA2 mutation is very low, but it could happen. Moreover, scientists continue to discover new BRCA1 and BRCA2 mutations and have not yet identified all potentially harmful ones. Therefore, it is possible that a person in this scenario with a "negative" test result actually has an as-yet unknown harmful BRCA1 or BRCA2 mutation that has not been identified.

It is also possible for people to have a mutation in a gene other than BRCA1 or BRCA2 that increases their cancer risk but is not detectable by the test used. People considering genetic testing for BRCA1 and BRCA2 mutations may want to discuss these potential uncertainties with a genetic counselor before undergoing testing.

What does an ambiguous or uncertain BRCA1 or BRCA2 test result mean?

Sometimes, a genetic test finds a change in BRCA1 or BRCA2 that has not been previously associated with cancer. This type of test result may be described as ambiguous (often referred to as a genetic variant of uncertain significance) because it isnt known whether this specific gene change affects a persons risk of developing cancer. One study found that 10 percent of women who underwent BRCA1 and BRCA2 mutation testing had this type of ambiguous result (18).

As more research is conducted and more people are tested for BRCA1 and BRCA2 mutations, scientists will learn more about these changes and cancer risk. Genetic counseling can help a person understand what an ambiguous change in BRCA1 or BRCA2 may mean in terms of cancer risk. Over time, additional studies of variants of uncertain significance may result in a specific mutation being re-classified as either harmful or clearly not harmful.

How can a person who has a positive test result manage their risk of cancer?

Several options are available for managing cancer risk in individuals who have a known harmful BRCA1 or BRCA2 mutation. These include enhanced screening, prophylactic (risk-reducing) surgery, and chemoprevention.

Enhanced Screening. Some women who test positive for BRCA1 and BRCA2 mutations may choose to start cancer screening at younger ages than the general population or to have more frequent screening. For example, some experts recommend that women who carry a harmful BRCA1 or BRCA2 mutation undergo clinical breast examinations beginning at age 25 to 35 years (19). And some expert groups recommend that women who carry such a mutation have a mammogram every year, beginning at age 25 to 35 years.

Enhanced screening may increase the chance of detecting breast cancer at an early stage, when it may have a better chance of being treated successfully. Women who have a positive test result should ask their health care provider about the possible harms of diagnostic tests that involve radiation (mammograms or x-rays).

Recent studies have shown that MRI may be more sensitive than mammography for women at high risk of breast cancer (20, 21). However, mammography can also identify some breast cancers that are not identified by MRI (22), and MRI may be less specific (i.e., lead to more false-positive results) than mammography. Several organizations, such as the American Cancer Society and the National Comprehensive Cancer Network, now recommend annual screening with mammography and MRI for women who have a high risk of breast cancer.

No effective ovarian cancer screening methods currently exist. Some groups recommend transvaginal ultrasound, blood tests for the antigen CA-125, and clinical examinations for ovarian cancer screening in women with harmful BRCA1 or BRCA2 mutations, but none of these methods appears to detect ovarian tumors at an early enough stage to reduce the risk of dying from ovarian cancer (23). For a screening method to be considered effective, it must have demonstrated reduced mortality from the disease of interest. This standard has not yet been met for ovarian cancer screening.

The benefits of screening for breast and other cancers in men who carry harmful mutations in BRCA1 or BRCA2 is also not known, but some expert groups recommend that men who are known to carry a harmful mutation undergo regular mammography as well as testing for prostate cancer. The value of these screening strategies remains unproven at present.

Prophylactic (Risk-reducing) Surgery. Prophylactic surgery involves removing as much of the "at-risk" tissue as possible. Women may choose to have both breasts removed (bilateral prophylactic mastectomy) to reduce their risk of breast cancer. Surgery to remove a woman's ovaries and fallopian tubes (bilateral prophylactic salpingo-oophorectomy) can help reduce her risk of ovarian cancer. Removing the ovaries also reduces the risk of breast cancer in premenopausal women by eliminating a source of hormones that can fuel the growth of some types of breast cancer.

No evidence is available regarding the effectiveness of bilateral prophylactic mastectomy in reducing breast cancer risk in men with a harmful BRCA1 or BRCA2 mutation or a family history of breast cancer. Therefore, bilateral prophylactic mastectomy for men at high risk of breast cancer is considered an experimental procedure, and insurance companies will not normally cover it.

Prophylactic surgery does not completely guarantee that cancer will not develop because not all at-risk tissue can be removed by these procedures. Some women have developed breast cancer, ovarian cancer, or primary peritoneal carcinomatosis (a type of cancer similar to ovarian cancer) even after prophylactic surgery. Nevertheless, the mortality reduction associated with this surgery is substantial: Research demonstrates that women who underwent bilateral prophylactic salpingo-oophorectomy had a nearly 80 percent reduction in risk of dying from ovarian cancer, a 56 percent reduction in risk of dying from breast cancer (24), and a 77 percent reduction in risk of dying from any cause (25).

Emerging evidence (25) suggests that the amount of protection that removing the ovaries and fallopian tubes provides against the development of breast and ovarian cancer may be similar for carriers of BRCA1 and BRCA2 mutations, in contrast to earlier studies (26).

Chemoprevention. Chemoprevention is the use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the recurrence of, cancer. Although two chemopreventive drugs (tamoxifen and raloxifene) have been approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of breast cancer in women at increased risk, the role of these drugs in women with harmful BRCA1 or BRCA2 mutations is not yet clear.

Data from three studies suggest that tamoxifen may be able to help lower the risk of breast cancer in BRCA1 and BRCA2 mutation carriers (27), including the risk of cancer in the opposite breast among women previously diagnosed with breast cancer (28, 29). Studies have not examined the effectiveness of raloxifene in BRCA1 and BRCA2 mutation carriers specifically.

Oral contraceptives (birth control pills) are thought to reduce the risk of ovarian cancer by about 50 percent both in the general population and in women with harmful BRCA1 or BRCA2 mutations (30).

What are some of the benefits of genetic testing for breast and ovarian cancer risk?

There can be benefits to genetic testing, regardless of whether a person receives a positive or a negative result.

The potential benefits of a true negative result include a sense of relief regarding the future risk of cancer, learning that one's children are not at risk of inheriting the family's cancer susceptibility, and the possibility that special checkups, tests, or preventive surgeries may not be needed.

A positive test result may bring relief by resolving uncertainty regarding future cancer risk and may allow people to make informed decisions about their future, including taking steps to reduce their cancer risk. In addition, people who have a positive test result may choose to participate in medical research that could, in the long run, help reduce deaths from hereditary breast and ovarian cancer.

What are some of the possible harms of genetic testing for breast and ovarian cancer risk?

The direct medical harms of genetic testing are minimal, but knowledge of test results may have harmful effects on a persons emotions, social relationships, finances, and medical choices.

People who receive a positive test result may feel anxious, depressed, or angry. They may have difficulty making choices about whether to have preventive surgery or about which surgery to have.

People who receive a negative test result may experience survivor guilt, caused by the knowledge that they likely do not have an increased risk of developing a disease that affects one or more loved ones.

Because genetic testing can reveal information about more than one family member, the emotions caused by test results can create tension within families. Test results can also affect personal life choices, such as decisions about career, marriage, and childbearing.

Violations of privacy and of the confidentiality of genetic test results are additional potential risks. However, the federal Health Insurance Portability and Accountability Act and various state laws protect the privacy of a persons genetic information. Moreover, the federal Genetic Information Nondiscrimination Act, along with many state laws, prohibits discrimination based on genetic information in relation to health insurance and employment, although it does not cover life insurance, disability insurance, or long-term care insurance.

Finally, there is a small chance that test results may not be accurate, leading people to make decisions based on incorrect information. Although inaccurate results are unlikely, people with these concerns should address them during genetic counseling.

What are the implications of having a harmful BRCA1 or BRCA2 mutation for breast and ovarian cancer prognosis and treatment?

A number of studies have investigated possible clinical differences between breast and ovarian cancers that are associated with harmful BRCA1 or BRCA2 mutations and cancers that are not associated with these mutations.

There is some evidence that, over the long term, women who carry these mutations are more likely to develop a second cancer in either the same (ipsilateral) breast or the opposite (contralateral) breast than women who do not carry these mutations. Thus, some women with a harmful BRCA1 or BRCA2 mutation who develop breast cancer in one breast opt for a bilateral mastectomy, even if they would otherwise be candidates for breast-conserving surgery. In fact, because of the increased risk of a second breast cancer among BRCA1 and BRCA2 mutation carriers, some doctors recommend that women with early-onset breast cancer and those whose family history is consistent with a mutation in one of these genes have genetic testing when breast cancer is diagnosed.

Breast cancers in women with a harmful BRCA1 mutation are also more likely to be "triple-negative cancers" (i.e., the breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein), which generally have poorer prognosis than other breast cancers.

Because the products of the BRCA1 and BRCA2 genes are involved in DNA repair, some investigators have suggested that cancer cells with a harmful mutation in either of these genes may be more sensitive to anticancer agents that act by damaging DNA, such as cisplatin. In preclinical studies, drugs called PARP inhibitors, which block the repair of DNA damage, have been found to arrest the growth of cancer cells that have BRCA1 or BRCA2 mutations. These drugs have also shown some activity in cancer patients who carry BRCA1 or BRCA2 mutations, and researchers are continuing to develop and test these drugs.

What research is currently being done to help individuals with harmful BRCA1 or BRCA2 mutations?

Research studies are being conducted to find new and better ways of detecting, treating, and preventing cancer in people who carry mutations in BRCA1 and BRCA2. Additional studies are focused on improving genetic counseling methods and outcomes. Our knowledge in these areas is evolving rapidly.

Information about active clinical trials (research studies with people) for individuals with BRCA1 or BRCA2 mutations is available on NCIs website. The following links will retrieve lists of clinical trials open to individuals with BRCA1 or BRCA2 mutations.

NCIs Cancer Information Service (CIS) can also provide information about clinical trials and help with clinical trial searches.

Do inherited mutations in other genes increase the risk of breast and/or ovarian tumors?

Yes. Although harmful mutations in BRCA1 and BRCA2 are responsible for the disease in nearly half of families with multiple cases of breast cancer and up to 90 percent of families with both breast and ovarian cancer, mutations in a number of other genes have been associated with increased risks of breast and/or ovarian cancers (2, 31). These other genes include several that are associated with the inherited disorders Cowden syndrome, Peutz-Jeghers syndrome, Li-Fraumeni syndrome, and Fanconi anemia, which increase the risk of many cancer types.

Most mutations in these other genes are associated with smaller increases in breast cancer risk than are seen with mutations in BRCA1 and BRCA2. However, researchers recently reported that inherited mutations in the PALB2 gene are associated with a risk of breast cancer nearly as high as that associated with inherited BRCA1 and BRCA2 mutations (32). They estimated that 33 percent of women who inherit a harmful mutation in PALB2 will develop breast cancer by age 70 years. The estimated risk of breast cancer associated with a harmful PALB2 mutation is even higher for women who have a family history of breast cancer: 58 percent of those women will develop breast cancer by age 70 years.

PALB2, like BRCA1 and BRCA2, is a tumor suppressor gene. The PALB2 gene produces a protein that interacts with the proteins produced by the BRCA1 and BRCA2 genes to help repair breaks in DNA. Harmful mutations in PALB2 (also known as FANCN) are associated with increased risks of ovarian, pancreatic, and prostate cancers in addition to an increased risk of breast cancer (13, 33, 34). Mutations in PALB2, when inherited from each parent, can cause a Fanconi anemia subtype, FA-N, that is associated with childhood solid tumors (13, 33, 35).

Although genetic testing for PALB2 mutations is available, expert groups have not yet developed specific guidelines for who should be tested for, or the management of breast cancer risk in individuals with, PALB2 mutations.

Go here to see the original:
BRCA1 and BRCA2: Cancer Risk and Genetic Testing Fact ...

23 pairs of chromosomes. One unique you.

Experience your ancestry in a new way! Get a breakdown of your global ancestry by percentages, connect with DNA relatives and more.

Get an even more comprehensive understanding of your genetics. Receive 65+ online reports on your ancestry, traits and health - and more.

You are made of cells. And the cells in your body have 23 pairs of chromosomes. Your chromosomes are made of DNA, which can tell you a lot about you. Explore your 23 pairs today.

Find out what your 23 pairs of chromosomes can tell you.

Your DNA analysis is performed in US laboratories that are certified to meet CLIA standardsthe Clinical Laboratory Improvement Amendments of 1988.

A CLIA-certified lab must meet certain quality standards, including qualifications for individuals who perform the test and other standards that ensure the accuracy and reliability of results.

We use leading technology to genotype your DNAa custom Illumina HumanOmniExpress-24 format chip.

Learn more about our process.

Provide your saliva sample from home. Mail it back to our lab in the same kit it came inthe postage is pre-paid.

We bring your genetics to you.

Learn more about how it works.

We hear from thousands of customers around the world who write in to tell us about their 23andMe experienceand the impact it has had on their life.

See stories that inspire us.

Here are just a few of the things people frequently ask about 23andMe. If you don't see your question here, get in touch with us.

23andMe was founded in 2006 to help people access, understand and benefit from the human genome.

We have more than one million genotyped customers around the world.

In 2015, 23andMe was granted authorization by the US Food and Drug Administration (FDA) to market the first direct-to-consumer genetic test.

23andMe offers two Personal Genetic Services: Health + Ancestry and Ancestry. Both services require submitting a saliva sample using our saliva collection kit that you send to the lab for analysis.

Our Health + Ancestry Service examines your genes to tell you about your ancestry, carrier status,* wellness and traits. We analyze, compile and distill the information extracted from your DNA into 65+ reports you can access online and share with family and friends. See full list of reports offered.

Our Ancestry Service helps you understand who you are, where you came from and your family story. We analyze, compile and distill your DNA information into reports on your Ancestry Composition, Haplogroups, Neanderthal Ancestry and provide a DNA Relatives tool to enable you to connect with people who share DNA with you.

If you have the Health + Ancestry Service you have access to the full 23andMe experience. If you only have the Ancestry Service, you can easily upgrade to the Health + Ancestry Service for $125 at any time which gives you access to all 65+ reports on ancestry, carrier status,* wellness and traits. To upgrade, log in to your 23andMe account and navigate to the Settings page. You will receive immediate access to your new health reports.

23andMe is the first and only genetic service available directly to you that includes reports that meet FDA standards for clinical and scientific validity.

Our rigorous quality standards:

You choose how your genetic information is used and shared with others. We tell you how those choices are implemented and how we collect, use and disclose your information.

*Our tests can be used to determine carrier status in adults from saliva collected using an FDA-cleared collection device (OrageneDX model OGD-500.001), but cannot determine if you have two copies of the genetic variant. The tests are not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On their own, carrier status tests are not intended to tell you anything about the health of your fetus, or your newborn child's risk of developing a particular disease later in life.

The Cystic Fibrosis carrier status test is indicated for the detection of 28 variants in the CFTR gene and is most relevant for people of Ashkenazi Jewish, European, and Hispanic/Latino descent. The Sickle Cell Anemia carrier status test is indicated for the detection of the HbS variant in the HBB gene and is most relevant for people of African descent. The carrier status tests related to hereditary hearing loss consist of two tests one indicated for the detection of two variants in the GJB2 gene which is most relevant for people of Ashkenazi Jewish and European descent, and one indicated for the detection of six variants in the SLC26A4 gene.

Get a breakdown of your global ancestry, connect with DNA relatives and more.

Receive 65+ online reports on your ancestry, traits and health - and more.

Your DNA can tell you about your family history. Reports include: Ancestry Composition, Haplogroups, Neanderthal Ancestry

Find and connect with relatives in the 23andMe database who share DNA with you.

If you are starting a family, find out if you are a carrier for an inherited condition. Example reports include: Cystic Fibrosis, Sickle Cell Anemia, Hereditary Hearing Loss

Learn how your genes play a role in your well-being and lifestyle choices. Example reports include: Deep Sleep, Lactose Intolerance, Saturated Fat and Weight

Explore what makes you unique, from food preferences to physical features. Example reports include: Male Bald Spot, Sweet vs. Salty, Unibrow

23andMe is the first and only genetic service available directly to you that includes reports that meet FDA standards for clinical and scientific validity.

23andMe was founded in 2006 to help people access, understand and benefit from the human genome.

We have more than one million genotyped customers around the world. Read more.

See what customers are saying about us. Read more.

You can make a difference by participating in research online, from anywhere. Read more.

We are here to help with your questions. No question is too big or small. Read more.

See the list of important policies below. Click to read more.

Your DNA can tell you about your family history. See sample report. See sample report.

Learn how your genes play a role in your well-being and lifestyle choices. See sample report. See sample report.

Explore what makes you unique, from food preference to physical features. See sample report. See sample report.

If you are starting a family, find out if you are a carrier for an inherited condition. See sample report. See sample report.

1 variant in the SACS gene; relevant for French Canadian descent

1 variant in the SLC12A6 gene; relevant for French Canadian descent

3 variants in the PKHD1 gene

10 variants in the HBB gene; relevant for Cypriot, Greek, Italian, Sardinian descent

1 variant in the BLM gene; relevant for Ashkenazi Jewish descent

2 variants in the PMM2 gene; relevant for Danish descent

28 variants in the CFTR gene; relevant for European, Hispanic/Latino, Ashkenazi Jewish descent

2 variants in the HSD17B4 gene

1 variant in the DLD gene; relevant for Ashkenazi Jewish descent

1 variant in the IKBKAP gene; relevant for Ashkenazi Jewish descent

3 variants in the FANCC gene; relevant for Ashkenazi Jewish descent

1 variant in the BCS1L gene; relevant for Finnish descent

1 variant in the G6PC gene; relevant for Ashkenazi Jewish descent

2 variants in the SLC37A4 gene

3 variants in the ALDOB gene; relevant for European descent

3 variants in the LAMB3 gene

1 variant in the LRPPRC gene; relevant for French Canadian descent

1 variant in the SGCA gene; relevant for Finnish descent

1 variant in the SGCB gene; relevant for Southern Indiana Amish descent

1 variant in the FKRP gene; relevant for European descent

3 variants in the ACADM gene; relevant for Northern European descent

2 variants in the BCKDHB gene; relevant for Ashkenazi Jewish descent

1 variant in the CLN5 gene; relevant for Finnish descent

3 variants in the PPT1 gene; relevant for Finnish descent

3 variants in the SMPD1 gene; relevant for Ashkenazi Jewish descent

1 variant in the NBN gene; relevant for Eastern European descent

2 variants in the GJB2 gene; relevant for Ashkenazi Jewish, European descent

6 variants in the SLC26A4 gene

23 variants in the PAH gene; relevant for Northern European descent

1 variant in the GRHPR gene; relevant for European descent

1 variant in the PEX7 gene

1 variant in the SLC17A5 gene; relevant for Finnish, Swedish descent

1 variant in the HBB gene; relevant for African descent

1 variant in the ALDH3A2 gene; relevant for Swedish descent

4 variants in the HEXA gene; relevant for Ashkenazi Jewish, Cajun descent

4 variants in the FAH gene; relevant for French Canadian, Finnish descent

1 variant in the PCDH15 gene; relevant for Ashkenazi Jewish descent

1 variant in the CLRN1 gene; relevant for Ashkenazi Jewish descent

1 variant in the PEX1 gene

*Our tests can be used to determine carrier status in adults from saliva collected using an FDA-cleared collection device (OrageneDX model OGD-500.001), but cannot determine if you have two copies of the genetic variant. The tests are not intended to diagnose a disease, or tell you anything about your risk for developing a disease in the future. On their own, carrier status tests are not intended to tell you anything about the health of your fetus, or your newborn child's risk of developing a particular disease later in life.

Our product is in English only, and due to the applicable regulations it is only available for customers with shipping addresses in the following countries.

If your country is not listed, visit the International site.

The rest is here:
23andMe - DNA Genetic Testing & Analysis