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Newswise TORONTO, September 6, 2017 The Ted Rogers Centre for Heart Research today announces that Dr. Raymond Kim is its newest scientific lead, guiding efforts at the countrys only clinic devoted to cardiac genomics.

The Ted Rogers Centre Cardiac Genome Clinic is Canadas first such program to investigate the genetic causes of heart failure in both children and adults. At one of the worlds only cardiac genome clinics, researchers use whole genome sequencing to help identify the cause, formulate appropriate treatment options and optimize the management of patients and family members.

Genomics is a major part of our mission to better understand the nature of heart failure in order to develop novel treatments and preventative strategies, said Dr. Mansoor Husain, executive director of the Ted Rogers Centre. We are excited to have Raymond on board to build a unique program that is set up to have a very positive impact on heart failure care across the lifespan.

Dr. Kim, one of a handful of dual-trained internal medicine and medical genetics specialists in Toronto, is a rising star in medical genetics. He holds appointments at the Division of Clinical and Metabolic Genetics at SickKids, at the Fred A. Litwin Family Centre in Genetic Medicine that is jointly run by UHN and Mount Sinai Hospital, and at the Princess Margaret Cancer Centre. His research interests include genomic medicine, rare disorder registries and weaving novel genetic technologies into patient care.

Dr. Kim will co-direct the Cardiac Genome Clinic along with fellow medical geneticist Dr. Rebekah Jobling (SickKids), who is medical geneticist in the SickKids Division of Clinical and Metabolic Genetics and molecular geneticist in its Genome Diagnostics Molecular Laboratory.

The clinic opens up the incredible opportunity for families facing cardiovascular issues to have a team of scientists search for answers in the genome, said Dr. Kim. Genome testing will gradually become a normalized part of care, and we are at the forefront of this evolution, and are already helping shape best practices in this area.The addition of unique team members like Dr. Jobling makes our team world-class.

Dr. Kim joins three other scientific leads of the Ted Rogers Centre for Heart Research: Dr. Seema Mital, Dr. Heather Ross, and Professor Craig Simmons who are respective experts in genetics, heart failure, and cell and tissue engineering. Together, they are helping direct a vast, collaborative effort to change the lives of Canadians who live with, or are at risk of, heart failure a costly disease that is a global epidemic.

ABOUT THE TED ROGERS CENTRE FOR HEART RESEARCH

The Ted Rogers Centre for Heart Research aims to develop new diagnoses, treatments and tools to prevent and individually manage heart failure Canadas fastest growing cardiac disease. Enabled by an unprecedented gift of $130 million from the Rogers family, the Centre was jointly conceived by its three partner organizations: The Hospital for Sick Children, University Health Network, and the University of Toronto. Together, they committed an additional $139 million toward the Centre representing a $270 million investment in basic science, translational and clinical research, innovation, and education in regenerative medicine, genomics, and the clinical care of children and adults. It is addressing heart failure across the lifespan. http://www.tedrogersresearch.ca / @trogersresearch

To transform the care of children and adults with heart failure through discovery, innovation and knowledge translation.

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New Medical Geneticists Join Ted Rogers Centre for Heart Research - Newswise (press release)

Dr. Krupp's NIH-ACMG Fellowship begins in September 2017 and will last 24 months. She will do five three-month rotations beginning at ACMG and then through the National Human Genome Research Institute (NHGRI), the National Heart, Lung and Blood Institute (NHLBI), the National Institute of Mental Health (NIMH), the National Institute on Minority Health and Health Disparities (NIMHD), and the Precision Medicine Initiative All of Us Research program, followed by a six-month elective.

"I feel privileged to be the first recipient of the NIH-ACMG Fellowship in Genomic Medicine Program Management," said Dr. Krupp. "Responsible leadership is key both to further develop our understanding of human genome variation and to best support genome based predictive medicine programs. This fellowship provides unprecedented opportunities to engage with leaders at NIH and ACMG as they provide contemporary management of such programs. This will foster leadership attributes invaluable for my career goal to contribute leadership oversight in genomic medicine research and program implementation."

Dr. Krupp earned her medical degree from the St. Louis University School of Medicine and is board certified in Anesthesiology. She completed a Pediatric Anesthesiology Fellowship at Children's Hospital and Regional Medical Center in Seattle, WA. Most recently, she was a fellow in Medical Genetics and Genomic Medicine at the University of Colorado School of Medicine. Dr. Krupp has been devoted to medical volunteer work throughout her career and has completed numerous volunteer medical assignments throughout the world including Venezuela, Peru, Haiti, Cambodia and the Dominican Republic.

About the American College of Medical Genetics and Genomics (ACMG) and ACMG Foundation

Founded in 1991, ACMG is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics. The American College of Medical Genetics and Genomics (www.acmg.net) provides education, resources and a voice for more than 2100 biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. The College's mission is to develop and sustain genetic initiatives in clinical and laboratory practice, education and advocacy. Three guiding pillars underpin ACMG's work: 1) Clinical and Laboratory Practice: Establish the paradigm of genomic medicine by issuing statements and evidence-based or expert clinical and laboratory practice guidelines and through descriptions of best practices for the delivery of genomic medicine. 2) Education: Provide education and tools for medical geneticists, other health professionals and the public and grow the genetics workforce. 3) Advocacy: Work with policymakers and payers to support the responsible application of genomics in medical practice. Genetics in Medicine, published monthly, is the official ACMG peer-reviewed journal. ACMG's website offers a variety of resources including Policy Statements, Practice Guidelines, Educational Resources, and a Find a Geneticist tool. The educational and public health programs of the American College of Medical Genetics and Genomics are dependent upon charitable gifts from corporations, foundations, and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Contact Kathy Beal, MBA

ACMG Media Relations,

kbeal@acmg.net

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SOURCE American College of Medical Genetics and Genomics

http://www.acmg.net

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Jennifer Krupp, MD is First Recipient of the New NIH-ACMG Fellowship in Genomic Medicine Program Management - PR Newswire (press release)

Shares of Sarepta Therapeutics soared 12 percent in early trading Wednesday after the biopharmaceutical company reported positive results from a clinical trial of an experimental medicine for Duchenne muscular dystrophy.

The drug, golodirsen, would be Sarepta's second to treat the rare, genetic disease, which causes muscle wasting and can be fatal before patients turn 30. Sarepta focuses on the discovery and development of precision genetic medicines to treat rare neuromuscular diseases.

The new study, conducted in Europe, involved 25 boys with confirmed deletions of the DMD gene amenable to skipping exon 53. Exons are part of the DNA code. The treatment targets a genetic mutation affecting about 8 percent of patients with DMD.

Sarepta's first drug for DMD, Exondys 51 approved on a conditional basis by the FDA last year pending more testing to confirm results treats a mutation affecting about 13 percent. Exondys 51 costs about $300,000 per year.

"Our goal is to treat 100 percent" of DMD suffers, Sarepta CEO Doug Ingram told CNBC's "Squawk Box." "The data that we have this morning shows we're on the right path."

The results, announced before Wall Street's open bell, showed that golodirsen increased production of the protein dystrophin to 1.02 percent of normal levels from about 0.095 percent without the drug. Analysts said those results were higher than expected, but scientists wonder whether that's enough to increase muscle strength and have a clinical benefit.

According to Sarepta, the underlying cause of DMD is a mutation in the gene for dystrophin, which is an essential protein involved in muscle fiber function. DMD occurs in one in every 3,500 to 5,000 males worldwide. Symptoms usually start in early childhood, usually between 3- and 5-years old. It primarily affects boys. But in rare cases can affect girls.

"Sarepta is a small company. We have already invested $1 billion fighting Duchenne muscular dystrophy. And we're not done yet," said Ingram, who was appointed as CEO in July. Ahead of Wednesday, Sarepta had a stock market value of $2.6 billion.

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Shares of drugmaker that targets gene mutations soar after positive muscular dystrophy study - CNBC

TUESDAY, Sept. 5, 2017 (HealthDay News) -- If a gym visit elicits more grimaces than grins, you might be genetically predisposed to dislike exercise, Dutch researchers suggest.

The notion that at least part of a penchant for enjoying exercise -- or not -- may be inherited came from tracking the exercise habits and feelings of several hundred sets of identical twins, fraternal twins, and non-twin siblings between the ages of 12 and 25.

The study team further found that people who enjoyed working out spent more time doing so. And that raises the prospect that new interventions might eventually help boost exercise pleasure among those who've inherited a bias against it.

"Despite the persistent general belief that exercise makes everyone feel better, this is not always the case," said study lead author Nienke Schutte.

"There are large differences in how people feel during and after exercise," Schutte said. She's a postdoctoral researcher in the department of public and occupational health with the VU Medical Center in Amsterdam.

"In our study," she added, "we submitted healthy adolescent twin pairs to a 20-minute exercise test on a cycle and a 20-minute exercise test on a treadmill. During and after the exercise tests, we asked them to indicate how they felt."

And in the end, Schutte said, "we showed that up to 37 percent of the differences in the subjective experience of exercise was due to genetics."

The study included 115 pairs of identical twins, 111 pairs of fraternal twins and 35 of their non-twin siblings. All of the study volunteers completed a 20-minute stationary bike ride and a 20-minute treadmill run. Both were characterized as "non-vigorous," although an additional bike ride had participants (which also included six non-twin sibling pairs) ride until they were exhausted.

During each ride and run participants were asked to describe how good or bad they felt, and whether the workout made them energetic, lively, jittery or tense. Lifestyle interviews were also conducted to gauge routine exercise habits.

In the end, the research team estimated that genetic predisposition accounted for anywhere between 12 to 37 percent of the variations seen in exercise enjoyment. And the more a person said they enjoyed exercising, the more often they routinely worked out.

That said, the study authors stressed that what they identified for now is simply an association between exercise pleasure and genetics, rather than a definitive case of cause and effect.

But "an important conclusion is that a one-size-fits-all approach to get people to exercise might not be very effective," Schutte said. "Now we know that how you feel during and shortly after an exercise bout is heritable, we can look for the actual genes that are involved."

And successful identification of such genes could mean that "in the future, depending on your genetic profile, interventions [could] be tailored to set realistic person-specific exercise goals," she added.

James Maddux is an emeritus professor in psychology with George Mason University in Fairfax, Va. He said that "the findings make sense," in his opinion.

"And given the accumulating research findings on the role of genes in individual differences among people on biological and psychological factors [such as] intelligence, personality [or] self-control, I'm not at all surprised," he added.

Maddux also suggested that the mere acknowledgement of a genetic underpinning to exercise enjoyment could end up being of practical benefit, even without knowing which specific genes are involved.

"You don't need to identify the genes that may be partly responsible for individual differences in the experience of pleasure and pain during exercise in order to use descriptions of those individual differences to design individualized exercise programs," he said.

What's more, said Maddux, "knowing that there is a genetic contribution may help the high-exercise-discomfort person engage in less self-blame, which can be demoralizing and discouraging. In fact, this could be useful information for personal trainers to pass along to their high-discomfort clients. It could help both of them be a little more patient."

The study was published in the journal Psychology of Sport and Exercise.

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Hate to Work Out? Your DNA May Be to Blame - Ravalli Republic

Researchers say that certain variations of the TOMM40 gene, located on the 19th chromosome outlined above, are heavily associated with developing Alzheimer's disease. Credit: National Center for Biotechnology Information, U.S. National Library of Medicine

The notorious genetic marker of Alzheimer's disease and other forms of dementia, ApoE4, may not be a lone wolf.

Researchers from USC and The University of Manchester have found that another gene, TOMM40, complicates the picture. Although ApoE4 plays a greater role in some types of aging-related memory ability, the researchers believe that TOMM40 may pose an even greater risk for other types.

TOMM40 and APOE genes are neighbors, adjacent to each other on chromosome 19, and they are sometimes used as proxies for one another in genetic studies. At times, scientific research has focused chiefly on one APOE variant, ApoE4, as the No. 1 suspect behind Alzheimer's and dementia-related memory decline. The literature also considers the more common variant of APOE, ApoE3, neutral in risk for Alzheimer's.

USC researchers believe their new findings raise a significant research question: Has TOMM40 been misunderstood as a sidekick to ApoE4 when it is really a mastermind, particularly when ApoE3 is present?

"Typically, ApoE4 has been considered the strongest known genetic risk factor for cognitive decline, memory decline, Alzheimer's disease or dementia-related onset," said T. Em Arpawong, the study's lead author and a postdoctoral fellow in the USC Dornsife College of Letters, Arts and Sciences' Department of Psychology.

"Although prior studies have found some variants of this other gene TOMM40 may heighten the risk for Alzheimer's disease, our study found that a TOMM40 variant was actually more influential than ApoE4 on the decline in immediate memorythe ability to hold onto new information," Arpawong explained.

Studies have shown that the influence of genes associated with memory and cognitive decline intensifies with age. That is why the scientists chose to examine immediate and delayed verbal test results over time in conjunction with genetic markers.

"An example of immediate recall is someone tells you a series of directions to get somewhere and you're able to repeat them back," said Carol A. Prescott, the paper's senior author and professor of psychology at USC Dornsife and professor of gerontology at the USC Davis School of Gerontology. "Delayed recall is being able to remember those directions a few minutes later, as you're on your way."

The study was published in the journal PLOS ONE on Aug. 11.

Tracking memory loss

The team of researchers from USC and The University of Manchester used data from two surveys: the U.S. Health and Retirement Study and the English Longitudinal Study of Ageing. Both data sets are nationally representative samples and include results of verbal memory testing and genetic testing.

The research team used verbal test results from the U.S. Health and Retirement Survey, collected from 1996 to 2012, which interviewed participants via phone every two years. The researchers utilized the verbal memory test scores of 20,650 participants, aged 50 and older who were tested repeatedly to study how their memory changed over time.

To test immediate recall, an interviewer read a list of 10 nouns and then asked the participant to repeat the words back immediately. For delayed recall, the interviewer waited five minutes and then asked the participant to recall the list. Test scores ranged from 0 to 10.

The average score for immediate recall was 5.7 words out of 10, and the delayed recall scoring average was 4.5 words out of 10. A large gap between the two sets of scores can signal the development of Alzheimer's or some other form of dementia.

"There is usually a drop-off in scores between the immediate and the delayed recall tests," Prescott said. "In evaluating memory decline, it is important to look at both types of memory and the difference between them. You would be more worried about a person who has scores of 10 and 5 than a person with scores of 6 and 4."

The first person is worrisome because five minutes after reciting the 10 words perfectly, he or she can recall only half of them, Prescott said. The other person wasn't perfect on the immediate recall test, but five minutes later, was able to remember a greater proportion of words.

To prevent bias in the study's results, the researchers excluded participants who reported that they had received a likely diagnosis of dementia or a dementia-like condition, such as Alzheimer's. They also focused on participants identified as primarily European in heritage to minimize population bias. Results were adjusted for age and sex.

One key innovation of the study is that the researchers used statistical methods to create scores that represent level and decline in delayed recall, separate from level and decline in immediate recall from the repeated assessments of memory. Most of the prior studies have used a total sum score for the two, a score from a single time-point or combined recall scores with other measures of cognition to investigate overall cognitive decline. By separating these components of recall, researchers had a better chance of detecting and explaining how genes affect each of these abilities differently.

The researchers compared the U.S. data to the results of an independent replication sample of participants, age 50 and up, in the English Longitudinal Study of Aging from 2002 to 2012. Interviews and tests were conducted every two years.

Genetic markers for memory

To investigate whether genes associated with immediate and delayed recall abilities, researchers used genetic data from 7,486 participants in the U.S. Health and Retirement Study and 6,898 participants in the English Longitudinal Study of Ageing.

The researchers examined the association between the immediate and delayed recall results with 1.2 million gene variations across the human genome. Only one, TOMM40, had a strong link to declines in immediate recall and level of delayed recall. ApoE4 also was linked but not as strongly.

"Our findings indicate that TOMM40 plays a larger role, specifically, in the decline of verbal learning after age 60," the scientists wrote. "Further, our analyses showed that there are unique effects of TOMM40 beyond ApoE4 effects on both the level of delayed recall prior to age 60 and decline in immediate recall after 60."

Unlike ApoE4, the ApoE3 variant is generally thought to have no influence on Alzheimer's disease or memory decline. However, the team of scientists found that adults who had ApoE3 and a risk variant of TOMM40 were more likely to have lower memory scores. The finding suggests that TOMM40 affects memoryeven when ApoE4 is not a factor.

The team suggested that scientists should further examine the association between ApoE3 and TOMM40 variants and their combined influence on decline in different types of learning and memory.

"Other studies may not have detected the effects of TOMM40," Prescott said. "The results from this study provide more evidence that the causes of memory decline are even more complicated than we thought before, and they raise the question of how many findings in other studies have been attributed to ApoE4 that may be due to TOMM40 or a combination of TOMM40 and ApoE4."

Explore further: Education does not protect against cognitive decline

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Which genetic marker is the ring leader in the onset of Alzheimer's disease? - Medical Xpress

Side effects are a very real consequence to some medication and they could be telling you something you may not know. According to mygeneRX, your genetics have a direct effect on how your body processes medication, this metabolism, in turn, may lead to severe side effects.

A DNA sample of a simple cheek swab can now be accurately profiled to determine your risk of side effects, which will allow you to adjust dosages and avoid certain medications altogether.

According to medical experts, personalised medicine will be the future of medicine as we know it. Personalised medicine is focused on tailoring treatment for the individual. According to mygeneRx, in order for the medication to have the desired effect and then be expelled from the body, proteins called enzymes break down the medication. Some individuals enzymes work more efficiently than others other people dont possess certain enzymes at all.

ALSO READ:Scientist may be able to reverse DNA and ageing

Medications act as inhibitors or inducers of enzymes affecting how the medication works and at what dosages.

According to mygeneRX, simple, non-invasive and affordable genetic testing analyses the genotypes associated with responsiveness to a range of medications, and gives your healthcare practitioner the knowledge to tailor your treatment accordingly. It means greater confidence in taking and prescribing medication.

A body that metabolises certain medications slower may need reduced dosages, whereas a body that has a rapid metabolism might require stronger dosages for the medication to have the desired outcome.

According to mygeneRX, Dr Danny Meyersfeld, a molecular biologist and the founder of DNAlysis biotechnology, says it is critical to understand the genetic make-up of a patient in relation to the prescription of medicine. If healthcare practitioners were to use genetics, heres what they could learn about prescribing the common painkiller codeine.

ALSO READ:Pupils enjoy National Science Week

Typically, the body produces an enzyme called CYP2D6 that breaks down the drug into its active ingredient, morphine, which provides pain relief. Yet up to 10% of patients have genetic variants that produce too little of the enzyme, so almost no codeine gets turned into morphine.

These people get little or no help for their pain. Similarly, about 10% of the population has too many copies of the gene that produces the enzyme, leading to overproduction. For them a little codeine can quickly turn to too much morphine, which can lead to a fatal overdose and side effects such as constipation, dizziness, drowsiness, nausea and vomiting, says Meyersfeld.

Typically, patients with cardiovascular diseases are on different medications such as blood thinners, beta blockers and statins, and with each one, the risk of adverse medicine interaction significantly increases. A genetic test for cardiac patients for drug response has shown to be more effective in guiding treatment decisions or improving outcomes.

He said mygeneRx tests for more than 150 medications including cardiovascular, psychiatry and pain management. It can be ordered online and the cheek swab is done in the privacy of your own home. According to mygeneRX, it is a simple process with substantial benefits.

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How your DNA can prevent medicine side effects - Centurion Rekord

A team of UC San Francisco researchers will receive $11.7 million over four years from the National Institutes of Health (NIH) to launch a new Program in Prenatal and Pediatric Genomic Sequencing (P3EGS) at UCSF. The program is aimed at pursuing equity in the implementation of genomic precision medicine for children and families in the San Francisco Bay Area.

Genomic precision medicine is a broad effort to connect the vast amounts of genetic sequencing data that have been collected in the past decades with information about human population health in order to understand why individuals respond differently to sickness and medical treatment, and to apply this knowledge toward developing more precise diagnostics and therapies targeted to the needs of particular patients and groups.

To advance equity in precision medicine within the Bay Area, the P3EGS team will recruit 1,100 families with children with potential prenatal or pediatric genetic disorders drawn from a diverse set of backgrounds, including medically underserved communities. P3EGS will not only provide state-of-the-art genomic assessments to these families, but also provide genetic counseling, develop software to aid in displaying and communicating genetic data in community clinics, and study the long-term benefits of providing genetic sequencing for these families and children as well as identify the barriers they face in accessing care.

The effort leverages the outstanding clinical, genomics, informatics, bioethics, health economics, and medical anthropology expertise that together form a robust genomics infrastructure at UCSF. The P3EGS team will be helmed by four leading members of the Institute for Human Genetics (IHG) at UCSF:

Neil Risch, PhD, the director of the UCSF Institute for Human Genetics, notes that P3EGS will be among the first users of the newly approved UCSF Whole Exome Sequencing service hosted by the Genomic Medicine Initiative, which he co-directs with Kwok.

Patients will be recruited from the diverse communities served by UCSF Benioff Childrens Hospital Oakland, UCSF Benioff Childrens Hospital San Francisco, UCSF Betty Irene Moore Womens Hospital, and Zuckerberg San Francisco General Hospital (ZSFGH).

Funding for the P3EGS program is part of $18.9 million being awarding by the NIH this year toward research accelerating the use of genome sequencing in clinical care at six sites across the United States, called the Clinical Sequencing Evidence-Generating Research (CSER2) Consortium. The consortium is funded by the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), both part of NIH, and it builds upon an earlier Clinical Sequencing Exploratory Research (CSER) Consortium, initiated in 2010, which included an award to Koenig and colleagues to study the ethics of informing family members of participants in cancer biobank research about unanticipated genetic findings.

The CSER2 awards are designed to support the development of methods needed to integrate genome sequencing into the practice of medicine, improve the discovery and interpretation of genomic variants, and investigate the impact of genome sequencing on health care outcomes. In addition, the funds are intended to generate innovative approaches and best practices to ensure that the effectiveness of genomic medicine can be applied to all individuals and groups, including diverse and underserved populations, and in health care settings that extend beyond academic medical centers.

The full press release about the CSER2 awards is available on the NHGRI website

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New UCSF Program Aims to Advance Equity in Genomic Medicine in the Bay Area - UCSF News Services

Brian J. O'Roak, Ph.D., assistant professor of molecular and medical genetics, OHSU, January 4, 2017. Credit: OHSU/John Valls

Autism spectrum disorder affects approximately one out of every 68 children in the United States. Despite expansive study, the origin and risk factors of the complex condition are not fully understood.

To better understand the root causes, an international team led by researchers at OHSU in Portland, Oregon has applied a new systematic analysis to a cohort of 2,300 families who have a single child affected with autism. The study focused on identifying and characterizing low-lying genetic mutations that may have been missed in previous research, given these mutations are only present in a fraction of the bulk DNA of an individual.

Known as postzygotic mosaic mutations, or PMMs, these genetic changes occur after the conception of the human zygote during the development cycle of a fetus. An individual will contain a mosaicor assortmentof mutated and non-mutated cells with the level of mosaicism depending on the time and location of the mutation's occurrence. This emerging class of genetic risk factors has recently been implicated in various neurologic conditions, however, their role in more complex disorders, such as autism, has been unclear.

Autism risk due to unexpected mosaic mutations

By comparing genetic sequencing data of these familiespart of the Simons Simplex Collection, a permanent repository of precisely characterized genetic samplesthe research team determined that approximately 11 percent of previously reported new mutations affecting a single DNA base, which were thought to have be present at the time of human conception, actually show evidence of the mutation occurring during the development process.

"This initial finding told us that, generally, these mosaic mutations are much more common than previously believed. We thought this might be the tip of a genetic iceberg waiting to be explored," said the study's principal investigator Brian O'Roak, Ph.D., an assistant professor of molecular and medical genetics in the OHSU School of Medicine.

To investigate this possibility, a custom approachleveraging next generation sequencing and molecular barcodes - was developed to both identify these low-level mutations, and also validate that they are, in fact, real and not technological artifacts. With this more sensitive method, the rate of potentially PMMs increased to 22 percent of the new mutations present in children.

The researchers then compared the rates of PMMs that result in different predicted effects on the genome in affected children and their unaffected siblings. This lead to an unexpected finding that so-called "silent" mosaic mutations were enriched in the affected children, contributing risk to approximately 2 percent of the individuals with autism in this cohort. These types of mutations are generally believed to be neutral, as they don't alter the genetic coding of proteins. However, the team found evidence that these mutations might actually be altering how genetic messages are stitched together.

The study also found preliminary evidence that mosaic mutations that alter the protein code of genes essential for development, or genes that resist mutations, are also enriched in individuals with autism. This contributes risk to an additional 1 to 2 percent of individuals with autism. Many of the PMMs occurred in some of the most highly validated autism risk genes identified to date, further suggesting that these mutations are contributing to autism genetic risk. Due to this, the research team believes that overall, mosaic mutations may contribute to autism risk in 3 to 4 percent of this cohort.

Understanding the timeline and location of mosaic mutations

Determining exactly when and where these mutations are occurring during development is challenging. The PMMs identified were present in 10 to 75 percent of the cells examined from the children's blood, suggesting that they likely occurred early in development. However, the exact timeline was not known.

By leveraging the unique family design of the Simons Simplex Collection cohort, O'Roak's team analyzed the parents' genomes and discovered that 6.8 percent of the supposedly "new" mutations present in children at conception could actually be traced back to a PMM that occurred early in the development of their parent. These mutations were generally present in 20 to 75 percent of the parents' blood cells, providing indirect evidence that many of the PMMs occurring in children did in fact happen very early during development and that they likely contribute mosaicism across the body, including in the brain.

"In addition to a need for broader research focused on the role that mosaicism plays in autism and related disorders, our data argue that physicians should be requiring more sensitive testing of both children and parents, when a new disorder-related genetic mutation is identified," O'Roak said. "These mutation can go from being in a few percent of the cells of a parent to 100 percent of the cells of a child. If present, at even low levels in the parents, the risk of additional children receiving this mutation is dramatically increased."

"Exonic mosaic mutations contribute risk for Autism Spectrum Disorder" published today in The American Journal of Human Genetics.

Explore further: Late-breaking mutations may play an important role in autism

More information: Deidre R. Krupp et al. Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.07.016

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Study identifies new genetic risk factor for developing autism ... - Medical Xpress

New Delhi [India], Aug 31 (ANI-BusinessWireIndia): PerkinElmer Health Sciences Pvt Ltd (PEHS), a screening and diagnostic laboratory of PerkinElmer, Inc. today announced that it has kicked off a series of seminars for neurologists, paediatricians and gynaecologists in Delhi, Mumbai, Hyderabad, Chennai and Mangalore, India.

These events serve as an ideal platform for discussing PerkinElmers recently launched affordable gene panels, whole exome sequencing (WES) and whole genome sequencing (WGS) services using next generation sequencing and other complementary assays to address the broad range of genetic disorders.

At the first conference, which took place in Delhi, Dr. Madhuri Hegde, Vice President and Chief Scientific Officer, PerkinElmer Diagnostic Laboratory Services, delivered a talk, Simplifying Genomics: Transforming Complexity into Meaning to a group of clinicians.

Starting her presentation, Dr. Hegde said, A growing interest in personalized medicine calls for genome sequencing in clinical diagnostics, but major challenges must be addressed before its full potential can be realized. This talk on a medical genetic testing algorithm will help clinicians select the most appropriate molecular diagnostic tool for each scenario. Dr. Hegde also serves on the board of ACMG Foundation for Genetics and Genomic Medicine and is an Adjunct Professor of Genetics and Paediatrics at Emory University and Georgia Institute of Technology.

Dr. IC Verma, a pioneer in the field of Genetic Medicine joined the session in Delhi and commented: This is a most exciting time in genetics. As a result of the new genomic sequencing technologies, we can arrive at a diagnosis in many more patients than before. Finding the variation in genes is leading to the development of new treatments for the genetic disorders. The medical professionals must take advantage of the genomic tests being offered in India at an affordable rate. The genetic tests enable screening of couples for being carriers of genetic disorders, genetic counseling and prenatal diagnosis to prevent disease and the possibility of new treatments.

Dr. Verma is a renowned medical geneticist. He received genetics training in the UK, USA & Switzerland. He is a Fellow of the Royal College of Physicians, London, the American Academy of Pediatrics, and the National Academy of Medical Sciences, New Delhi. He has received a number of national awards Ranbaxy Science Award, ICMR, NAMS and BC Roy Medical Council award. He is a Member and Vice-chairman of the Ethics Committee of the International Human Genome Organization (HUGO) and serves as an adviser in genetics to the WHO in Geneva, and to Roche Genetics in Basel.

The launch of our genetics service is all about providing quality and specialized service to clinicians in India. Dr. Hegde brings our customers high confidence in PerkinElmers quality sample analysis and reporting, said Jayashree Thacker, President, PerkinElmer India. We have been observing a high demand of sequencing services for rare inherited disease. Combining these offerings with our current portfolio will help address the evolving needs of our customers.

PerkinElmer now offers its customers a global genomic lab testing platform that performs screening and diagnostic testing, specializing in newborn screening and high throughput next generation sequencing for rare inherited diseases. (ANI-BusinessWireIndia)

This is published unedited from the ANI feed.

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PerkinElmer hosts Medical Genomics Seminars in India - India.com

A new genetics study adds fuel to the debate about muscle aches that have been reported by many people taking popular cholesterol-lowering drugs called statins.

About 60 percent of people of European descent carry a genetic variant that may make them more susceptible to muscle aches in general. But counterintuitively, these people had a lower risk of muscle pain when they took statins compared with placebos, researchers report August 29 in the European Heart Journal.

Millions of people take statins to lower cholesterol and fend off the hardening of arteries. But up to 78 percent of patients stop taking the medicine. One common reason for ceasing the drugs use is side effects, especially muscle pain, says John Guyton, a clinical lipidologist at Duke University School of Medicine.

It has been unclear, however, whether statins are to blame for the pain. In one study, 43 percent of patients who had muscle aches while taking at least one type of statin were also pained by other types of statin (SN: 5/13/17, p. 22). But 37 percent of muscle-ache sufferers in that study had pain not related to statin use. Other clinical trials have found no difference in muscle aches between people taking statins and those not taking the drugs.

The new study hints that genetic factors, especially ones involved in the immune systems maintenance and repair of muscles, may affect peoples reactions to statins. This is a major advance in our understanding about myalgia, or muscle pain, says Guyton, who was not involved in the study.

People with two copies of the common form of the gene LILRB5 tend to have higher-than-usual blood levels of two proteins released by injured muscles, creatine phosphokinase and lactate dehydrogenase. Higher levels of those proteins may predispose people to more aches and pains. In an examination of data from several studies involving white Europeans, people with dual copies of the common variant were nearly twice as likely to have achy muscles while taking statins as people with a less common variant, Moneeza Siddiqui of the University of Dundee School of Medicine in Scotland and colleagues discovered.

But when researchers examined who had pain when taking statins versus placebos, those with two copies of the common variant seemed to be protected from getting statin-associated muscle pain. Why is not clear.

People with double copies of the common form of the gene who experience muscle pain may stop taking statins because they erroneously think the drugs are causing the pain, study coauthor Colin Palmer of the University of Dundee said in a news release.

The less common version of the gene is linked to reduced levels of the muscle-damage proteins, and should protect against myalgia. Yet people with this version of the gene were the ones more likely to develop muscle pain specifically linked to taking statins during the trials.

The finding suggests that when people with the less common variant develop muscle pain while taking statins, the effect really is from the drugs, the researchers say.

But researchers still dont know the nitty-gritty details of how the genetic variants promote or protect against myalgia while on statins. Neither version of the gene guarantees that a patient will develop side effects or that they wont. The team proposes further clinical trials to unravel interactions between the gene and the drugs.

More study is needed before doctors can add the gene to the list of tests patients get, Guyton says. I dont think were ready to put this genetic screen into clinical practice at all, he says. For now, its much easier just to give the patient the statin and see what happens.

More here:
Muscle pain in people on statins may have a genetic link - Science News Magazine

In a step that heralds a new era in cancer treatment, the U.S. Food and Drug Administration said Wednesday it has approved a form of gene therapy that is highly effective at fighting an aggressive form of leukemia in young patients with no other options.

The treatment, to be marketed under the name Kymriah, is neither a pill nor an injection, but a personalized medicine service that functions as a living drug. Patients would have their bodys own disease-fighting T cells fortified and multiplied in a lab, then get the cells back to help them fight their cancer.

In clinical trials of 88 patients with a relapsing or treatment-resistant form of acute lymphoblastic leukemia, 73 went into remission after receiving the experimental treatment.

FDA Commissioner Scott Gottlieb, himself a survivor of blood cancer, predicted that this new approach to cancer treatment will change the face of modern medicine.

Cancer researchers and physicians outside the agency shared Gottliebs enthusiasm.

Dr. Crystal L. Mackall, associate director of Stanford Universitys Cancer Institute, called Kymriah a transformative therapy. It represents an entirely new class of cancer therapies that holds promise for all cancer patients.

Acute lymphoblastic leukemiais the most common form of pediatric cancer, affecting some 3,000 children and young adults yearly in the United States. Though it is considered highly curable in most patients, about 600 each year either do not respond to chemotherapy or see their leukemia return after an initial round of successful treatment.

Those patients dont make it none of them do, said Dr. Stephan A. Grupp, director of the cancer immunotherapy program at Childrens Hospital of Philadelphia, who administered the first course of Kymriah five years ago when it was an experimental treatment called CTL019.

That initial patient, 7-year-old Emily Whitehead of Philipsburg, Pa., saw her leukemia remit completely within three weeks of getting the treatment. Now 12, she was among those calling on the FDA to approve Kymriah for other patients like her.

Certainly for blood cancers, this is a game-changer, Grupp said. Adapting this therapy for patients with solid tumors, he said, will be the work of the next five years.

The new approach was designed to fight some of the most stubborn cancers by giving the bodys immune system a very specific assist.

It starts by harvesting a cancer patients T cells, the warriors of the immune system. The cells are delivered to a specialized lab where scientists alter their DNA, essentially reprogramming them to target cancer cells. These reengineered cells are called chimeric antigen receptor T cells, or CAR-T cells.

The new and improved cells are copied millions of times before theyre sent back to the patient. Once infused into the bloodstream, the CAR-T cells are much better equipped to hunt down and kill cancer cells, wherever they may hide.

Novartis, the company that developed Kymriah, intends to have 32 certified treatment centers up and running by the end of 2018. Patients up to the age of 25 would go to one of these centers to have their T cells harvested and later reintroduced in their modified form.

The cells themselves will be genetically engineered at a Novartis manufacturing facility in Morris Plains, N.J.

Kymriah is the first CAR-T treatment to come before the FDA, but it wont be the last. No fewer than 76 CAR-T treatments are currently under review at the FDA, and Gottlieb predicted that other approvals would follow.

Therapies that would operate in similar ways engineering the immune systems T cells to fight disease more effectively are under investigation for a host of other conditions, including HIV/AIDS, genetic and autoimmune disorders and other forms of cancer.

Todays FDA ruling is a milestone, said Dr. David Maloney, medical director of cellular immunotherapy at Fred Hutchinson Cancer Research Center in Seattle. This is just the first of what will soon be many new immunotherapy-based treatments for a variety of cancers.

Novartis, the Swiss pharmaceutical company that is gearing up to provide Kymriah to as many as 600 patients a year, said it would charge $475,000 for the treatment.

Novartis representatives said they calculated a cost-effective price for the therapy that fell between $600,000 and $750,000. But the company chose instead to charge a price that it said would cover costs, and to introduce a novel approach to billing. Chief Executive Joseph Jimenez said the company will not charge hospitals for the therapy if the patient does not fully respond in a given period of time.

The company also said it will launch a patient assistance program for those who are uninsured or underinsured, and provide some travel assistance for patients and caregivers seeking the treatment.

Gottlieb touted Kymriahs approval as a turning point for the FDA as well. Novartis application for Kymriah came just seven months ago. The agency tagged the application with two designations that ensured its speedy review.

First proposed in 1972, the idea of correcting or enhancing genes to treat disease has a history buoyed by promise but also buffeted by failures. With recent advances in genomic medicine, cell biology and genetic engineering, efforts to locate and edit the genes and cells that play a key role in disease have injected new hope for such treatments.

Gene and cell therapies that target the immune system for enhancement have been particularly promising. They do, however, come with risks specifically, that the activation of immune cells will run amok, sparking reactions ranging from rash and itching to fever and flu-like symptoms that can lead to death.

In approving Kymriah, the FDA warned that it has the potential to cause severe side effects, including cytokine release syndrome, an overreaction to the activation and proliferation of immune cells that causes high fever and flu-like symptoms, and neurological events. Both can be life-threatening. Kymriah can also cause serious infections, low blood pressure, acute kidney injury, fever and low oxygen levels.

The FDA called for continuing safety studies of the new therapy.

melissa.healy@latimes.com

@LATMelissaHealy

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In 2013, University of Virginia researcher Michael McConnell published research that would forever change how scientists study brain cells.

McConnell and a team of nationwide collaborators discovered a genetic mosaic in the brains neurons, proving that brain cells are not exact replicas of each other, and that each individual neuron contains a slightly different genetic makeup.

McConnell, an assistant professor in the School of Medicines Department of Biochemistry and Molecular Genetics, has been using this new information to investigate how variations in individual neurons impact neuropsychiatric disorders like schizophrenia and epilepsy. With a recent $50,000 grant from the Bow Foundation, McConnell will expand his research to explore the cause of a rare genetic disorder known as GNAO1 so named for the faulty protein-coding gene that is its likely source.

GNAO1 causes seizures, movement disorders and developmental delays. Currently, only 50 people worldwide are known to have the disease. The Bow Foundation seeks to increase awareness so that other probable victims of the disorder can be properly diagnosed and to raise funds for further research and treatment.

UVA Today recently sat down with McConnell to find out more about how GNAO1 fits into his broader research and what his continued work means for all neuropsychiatric disorders.

Q. Can you explain the general goals of your lab?

A. My lab has two general directions. One is brain somatic mosaicism, which is a finding that different neurons in the brain have different genomes from one another. We usually think every cell in a single persons body has the same blueprint for how they develop and what they become. It turns out that blueprint changes a little bit in the neurons from neuron to neuron. So you have slightly different versions of the same blueprint and we want to know what that means.

The second area of our work focuses on a new technology called induced pluripotent stem cells, or iPSCs. The technology permits us to make stem cell from skin cells. We can do this with patients, and use the stem cells to make specific cell types with same genetic mutations that are in the patients. That lets us create and study the persons brain cells in a dish. So now, if that person has a neurological disease, we can in a dish study that persons disease and identify drugs that alter the disease. Its a very personalized medicine approach to that disease.

Q. Does cell-level genomic variety exist in other areas of the body outside the central nervous system?

A. Every cell in your body has mutations of one kind or another, but brain cells are there for your whole life, so the differences have a bigger impact there. A skin cell is gone in a month. An intestinal cell is gone in a week. Any changes in those cells will rarely have an opportunity to cause a problem unless they cause a tumor.

Q. How does your research intersect with the goals of the Bow Foundation?

A. Let me back up to a little bit of history on that. When I got to UVA four years ago, I started talking quite a lot with Howard Goodkin and Mark Beenhakker. Mark is an assistant professor in pharmacology. Howard is a pediatric neurologist and works with children with epilepsy. I had this interest in epilepsy and UVA has a historic and current strength in epilepsy research.

We started talking about how to use iPSCs the technology that we use to study mosaicism to help Howards patients. As we talked about it and I learned more about epilepsy, we quickly realized that there are a substantial number of patients with epilepsy or seizure disorders where we cant do a genetic test to figure out what drug to use on those patients.

Clinical guidance, like Howards expertise, allows him to make a pretty good diagnosis and know what drugs to try first and second and third. But around 30 percent of children that come in with epilepsy never find the drug that works, and theyre in for a lifetime of trial-and-error. We realized that we could use iPSC-derived neurons to test drugs in the dish instead of going through all of the trial-and-error with patients. Thats the bigger project that weve been moving toward.

The Bow Foundation was formed by patient advocates after this rare genetic mutation in GNAO1 was identified. GNAO1 is a subunit of a G protein-coupled receptor; some mutations in this receptor can lead to epilepsy while others lead to movement disorders.

Were still trying to learn about these patients, and the biggest thing the Bow Foundation is doing is trying to address that by creating a patient registry. At the same time, the foundation has provided funds for us to start making and testing iPSCs and launch this approach to personalized medicine for epilepsy.

In the GNAO1 patients, we expect to be able to study their neurons in a dish and understand why they behave differently, why the electrical activity in their brain is different or why they develop differently.

Q. What other more widespread disorders, in addition to schizophrenia and epilepsy, are likely to benefit from your research?

A. Im part of a broader project called the Brain Somatic Mosaicism Network that is conducting research on diseases that span the neuropsychiatric field. Our lab covers schizophrenia, but other nodes within that network are researching autism, bipolar disorder, Tourette syndrome and other psychiatric diseases where the genetic cause is difficult to identify. Thats the underlying theme.

Read more:
Researcher Seeks to Unravel the Brain's Genetic Tapestry to Tackle Rare Disorder - University of Virginia

In 2007, DNA pioneer James Watson became the first person to have his entire genome sequencedmaking all of his 6 billion base pairs publicly available for research. Well, almost all of them. He left one spot blank, on the long arm of chromosome 19, where a gene called APOE lives. Certain variations in APOE increase your chances of developing Alzheimers, and Watson wanted to keep that information private.

Except it wasnt. Researchers quickly pointed out you could predict Watsons APOE variant based on signatures in the surrounding DNA. They didnt actually do it, but database managers wasted no time in redacting another two million base pairs surrounding the APOE gene.

This is the dilemma at the heart of precision medicine: It requires people to give up some of their privacy in service of the greater scientific good. To completely eliminate the risk of outing an individual based on their DNA records, youd have to strip it of the same identifying details that make it scientifically useful. But now, computer scientists and mathematicians are working toward an alternative solution. Instead of stripping genomic data, theyre encrypting it.

Gill Bejerano leads a developmental biology lab at Stanford that investigates the genetic roots of human disease. In 2013, when he realized he needed more genomic data, his lab joined Stanford Hospitals Pediatrics Departmentan arduous process that required extensive vetting and training of all his staff and equipment. This is how most institutions solve the privacy perils of data sharing. They limit who can access all the genomes in their possession to a trusted few, and only share obfuscated summary statistics more widely.

So when Bejerano found himself sitting in on a faculty talk given by Dan Boneh, head of the applied cryptography group at Stanford, he was struck with an idea. He scribbled down a mathematical formula for one of the genetic computations he uses often in his work. Afterward, he approached Boneh and showed it to him. Could you compute these outputs without knowing the inputs? he asked. Sure, said Boneh.

Last week, Bejerano and Boneh published a paper in Science that did just that. Using a cryptographic genome cloaking method, the scientists were able to do things like identify responsible mutations in groups of patients with rare diseases and compare groups of patients at two medical centers to find shared mutations associated with shared symptoms, all while keeping 97 percent of each participants unique genetic information completely hidden. They accomplished this by converting variations in each genome into a linear series of values. That allowed them to conduct any analyses they needed while only revealing genes relevant to that particular investigation.

Just like programs have bugs, people have bugs, says Bejerano. Finding disease-causing genetic traits is a lot like spotting flaws in computer code. You have to compare code that works to code that doesnt. But genetic data is much more sensitive, and people (rightly) worry that it might be used against them by insurers, or even stolen by hackers. If a patient held the cryptographic key to their data, they could get a valuable medical diagnosis while not exposing the rest of their genome to outside threats. You can make rules about not discriminating on the basis of genetics, or you can provide technology where you cant discriminate against people even if you wanted to, says Bejerano. Thats a much stronger statement.

The National Institutes of Health have been working toward such a technology since reidentification researchers first began connecting the dots in anonymous genomics data. In 2010, the agency founded a national center for Integrating Data for Analysis, Anonymization and Sharing housed on the campus of UC San Diego. And since 2015, iDash has been funding annual competitions to develop privacy-preserving genomics protocols. Another promising approach iDash has supported is something called fully homomorphic encryption, which allows users to run any computation they want on totally encrypted data without losing years of computing time.

Kristen Lauter, head of cryptography research at Microsoft, focuses on this form of encryption, and her team has taken home the iDash prize two years running. Critically, the method encodes the data in such a way that scientists dont lose the flexibility to perform medically useful genetic tests. Unlike previous encryption schemes, Lauters tool preserves the underlying mathematical structure of the data. That allows computers to do the math that delivers genetic diagnoses, for example, on totally encrypted data. Scientists get a key to decode the final results, but they never see the source.

This is extra important as more and more genetic data moves off local servers and into the cloud. The NIH lets users download human genomic data from its repositories, and in 2014, the agency started letting people store and analyze that data in private or commercial cloud environments. But under NIHs policy, its the scientists using the datanot the cloud service providerresponsible with ensuring its security. Cloud providers can get hacked, or subpoenaed by law enforcement, something researchers have no control over. That is, unless theres a viable encryption for data stored in the cloud.

If we dont think about it now, in five to 10 years a lot peoples genomic information will be used in ways they did not intend, says Lauter. But encryption is a funny technology to work with, she says. One that requires building trust between researchers and consumers. You can propose any crazy encryption you want and say its secure. Why should anyone believe you?

Thats where federal review comes in. In July, Lauters group, along with researchers from IBM and academic institutions around the world launched a process to standardize homomorphic encryption protocols. The National Institute for Standards and Technology will now begin reviewing draft standards and collecting public comments. If all goes well, genomics researchers and privacy advocates might finally have something they can agree on.

Originally posted here:
To Protect Genetic Privacy, Encrypt Your DNA - WIRED

Dr. Alexandre R. Colas is an assistant professor at SBP. Credit: James Short

Researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP), the Cardiovascular Institute at Stanford University and other institutions were surprised to discover that the four genes in the Id family play a crucial role in heart development, telling undifferentiated stem cells to form heart tubes and eventually muscle. While Id genes have long been known for their activity in neurons and blood cells, this is the first time they've been linked to heart development. These findings give scientists a new tool to create large numbers of cardiac cells to regenerate damaged heart tissue. The study was published in the journal Genes & Development.

"It has always been unclear what intra-cellular mechanism initiates cardiac cell fate from undifferentiated cells," says Alexandre Colas, Ph.D., assistant professor in the Development, Aging and Regeneration Program at SBP and corresponding author on the paper. "These genes are the earliest determinants of cardiac cell fate. This enables us to generate unlimited amounts of bona fide cardiac progenitors for regenerative purposes, disease modeling and drug discovery."

The international team, which included researchers from the International Centre for Genetic Engineering and Biotechnology in Italy, University Pierre and Marie Curie in France and the University of Coimbra in Portugal, combined CRISPR-Cas9 gene editing, high-throughput microRNA screening and other techniques to identify the role Id genes play in heart development.

In particular, CRISPR played a crucial role, allowing them to knock out all four Id genes. Previous studies had knocked out some of these genes, which led to damaged hearts. However, removing all four genes created mouse embryos with no hearts at all. This discovery comes after a decades-long effort to identify the genes responsible for heart development.

"This is a completely unanticipated pathway in making the heart," says co-author Mark Mercola, Ph.D., professor of Medicine at Stanford and adjunct professor at SBP. "People have been working for a hundred years to figure out how the heart is specified during development. Nobody in all that time had ever implicated the Id protein."

Further study showed Id genes enable heart formation by turning down the Tcf3 and Foxa2 proteins, which inhibit the process, and turning up Evx1, Grrp1 and Mesp1, which support the process.

In addition to contributing a new chapter in the understanding of heart development, this study illuminates a powerful technique to screen for protein function in complex phenotypical assays, which was previously co-developed by Colas and Mercola. This technology could have wide-spread impact throughout biology.

"On a technical level, this project succeeded because it combined high-throughput approaches with stem cells to functionally scan the entire proteome for individual proteins involved in making heart tissue," says Mercola. "It shows that we can effectively walk through the genome to find genes that control complex biology, like making heart cells or causing disease."

Understanding this pathway could ultimately jumpstart efforts to use stem cells to generate heart muscle and replace damaged tissue. In addition, because Id proteins are the earliest known mechanism to control cardiac cell fate, this work is an important milestone in understanding cardiovascular developmental biology.

"We've been influenced by the skeletal muscle development field, which found the regulator of myogenic lineage, or myoD," says Colas. "For decades, we have been trying to find the cardiac equivalent. The fact that Id genes are sufficient to direct stem cells to differentiate towards the cardiac lineage, and that you don't have a heart when you ablate them from the genome, suggests the Id family collectively is a candidate for cardioD."

Explore further: Discovery of a key regulatory gene in cardiac valve formation

More information: Thomas J. Cunningham et al, Id genes are essential for early heart formation, Genes & Development (2017). DOI: 10.1101/gad.300400.117

More here:
Id genes play surprise role in cardiac development - Medical Xpress

Ross Pomeroy | August 18, 2017 | Real Clear Science

Chiropractic, homeopathy, acupuncture, juice diets, and other forms of unproven alternative medicine cannot cure cancer, no matter what some quacks might claim.

[A]s a newstudypublished in theJournal of the National Cancer Institutemakes painfully clear, as a treatment for cancer, alternative medicine does not cure; it kills.

A team of scientists from Yale University perused theNational Cancer Database, a collection of 34 million records of cancer patients along with their treatments and outcomes, to identify patients who elected to forgo conventional cancer treatments like chemotherapy, radiotherapy, and surgery in favor of alternative medicine.

After five years, 78.3% of subjects who received conventional treatments were still alive, compared to only 54.7% of subjects who used alternative medicine. Even more startling, breast cancer patients who used alternative medicine were five times more likely to die. Colorectal cancer patients were four times more likely to die. Lung cancer patients were twice as likely to die.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Alternative Medicine Kills Cancer Patients, Study Finds

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Alternative medicine can kill you - Genetic Literacy Project

Of the nearly 4 million women in the United States who have had either breast cancer or ovarian cancer, at least 1.5 million have a high risk of carrying certain types of genetic mutations that could increase their risk for additional cancers in the future.

And although the mutations, including those that affect the BRCA1 and BRCA2 genes, can be identified through a simple blood or saliva test, more than 80 percent of those women have not taken the test or even discussed it with a health care provider, according to a new study from the UCLA Fielding School of Public Health.

The study is published online August 18 in the peer-reviewed Journal of Clinical Oncology.

"Many of these women have inherited genetic changes that put them and their family members at risk for future cancers," said Dr. Christopher Childers, a resident physician in the department of surgery at the David Geffen School of Medicine at UCLA and the study's lead author. "Identifying a mutation is often important for surgical decision-making and cancer therapy, but its importance extends further than that. If individuals are aware that they have these mutations, they can take steps to lower their future cancer risk."

Childers said people who know they have the mutations would be advised to undergo more frequent and specialized screening (such as breast MRI), consider preventive medications, undergo risk-reducing surgery or make lifestyle modifications (including improving diet and exercise habits, and stopping smoking).

Testing for BRCA1 and BRCA2 mutations, which are still the leading risk factors for inherited breast and ovarian cancer, has been available since the mid-1990s. But scientists now know that mutations in several other genes can increase the risk for breast and ovarian cancers; those mutations can also be detected by contemporary genetic tests.

The researchers examined data from the 2005, 2010 and 2015 National Health Interview Surveys, which are conducted by the Centers for Disease Control and Prevention. Then, drawing from the National Cancer Center Network's guidelines for managing care for people with cancer, the scientists identified five criteria to determine women for whom the genetic test would be most beneficial:

Of 47,218 women whose records were reviewed, 2.7 percent had had breast cancer. Among those who met at least one of these four criteria, 29 percent had discussed the genetic test with a health care provider, 20.2 percent were advised to undergo the test, and only 15.3 percent had taken it.

Some 0.4 percent of women in the survey had had ovarian cancer. Of them, 15.1 percent discussed the genetic test with a health care provider, 13.1 percent were advised to undergo the test and just 10.5 percent had taken it.

Based on those figures, the UCLA researchers estimated that 1.2 million to 1.3 million women in the U.S. who would be most likely to benefit from the test have not taken it.

"Many women are not receiving vital information that can aid with cancer prevention and early detection for them and their family," said co-author Kimberly Childers, a genetic counselor and regional manager of the Providence Health and Services Southern California's clinical genetics and genomics program. "Thus, we have identified an incredible unmet need for genetic testing across the country."

The paper suggests some reasons that so few women have undergone the test, including that NCCN guidelines have changed over the years, and the relatively small number of board-certified genetic counselors who specialize in cancer testing. (The researchers also note that genetic counselors are unevenly distributed throughout the country, with 500 in California but only five each in Wyoming, Alaska, Missouri and Mississippi.)

"Also, when women change doctors, their new physicians may not be aware of their histories or of the new eligibility guidelines," said James Macinko, professor of health policy and management and of community health sciences at the Fielding School, and the study's senior author.

The study has some limitations, including that data was self-reported and not verified by medical records, and that subjects may not have accurately remembered whether they discussed or took the genetic test.

Explore further: Genetic predisposition to breast cancer due to non-brca mutations in ashkenazi Jewish women

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Few women with history of breast cancer and ovarian cancer take a recommended genetic test - Medical Xpress

VIDEO Life Lessons: Next generation...

When Audrey Lapidus 10-month old son, Calvin, didnt reach normal milestones like rolling over or crawling, she knew something was wrong.

He was certainly different from our first child, said Lapidus, of Los Angeles. He had a lot of gastrointestinal issues and we were taking him to the doctor quite a bit.

Four specialists saw Calvin and batteries of tests proved inconclusive. Still, Lapidus persisted.

I was pushing for even more testing, and our geneticist at UCLA said, If you can wait one more month, were going to be launching a brand new test called exome sequencing, she said. We were lucky to be in the right place at the right time and get the information we did.

In 2012, Calvin Lapidus became the first patient to undergo exome sequencing at UCLA. He was subsequently diagnosed with a rare genetic condition known as Pitt-Hopkins Syndrome, which is most commonly characterized by developmental delays, possible breathing problems, seizures and gastrointestinal problems.

Though there is no cure for Pitt-Hopkins, finally having a diagnosis allowed Calvin to begin therapy.

The diagnosis gave us a point to move forward from, rather than just existing in that scary no-mans land where we knew nothing, Lapidus said.

Unfortunately, there are a lot of people living in that no-mans land, desperate for any type of answers to their medical conditions, said Dr. Stanley Nelson, professor of human genetics and pathology and laboratory medicine at the David Geffen School of Medicine at UCLA. Many families suffer for years without so much as a name for their condition.

What exome sequencing allows doctors to do is to analyze more than 20,000 genes at once, with one simple blood test.

In the past, genetic testing was done one gene at a time, which is time-consuming and expensive.

Rather than testing one sequential gene after another, exome sequencing saves time, money and effort, said Dr. Julian Martinez-Agosto, a pediatrician and researcher at the Resnick Neuropsychiatric Hospital at UCLA.

The exome consists of all the genomes exons, which are the coding portion of genes. Clinical exome sequencing is a test for identifying disease-causing DNA variants within the 1 percent of the genome which codes for proteins, the exons, or flanks the regions which code for proteins, called splice junctions.

To date, mutations in the protein-coding parts of genes accounts for nearly 85 percent of all mutations known to cause genetic diseases, so surveying just this portion of the genome is an efficient and powerful diagnostic tool. Exome sequencing can help detect rare disorders like spinocerebellar ataxia, which progressively diminishes a persons movements, and suggest the likelihood of more common conditions like autism spectrum disorder and epilepsy.

More than 4,000 adults and children have undergone exome testing at UCLA since 2012. Of difficult to solve cases, more than 30 percent are solved through this process, which is a dramatic improvement over prior technologies. Thus, Nelson and his team support wider use of genome-sequencing techniques and better insurance coverage, which would further benefit patients and resolve diagnostically difficult cases at much younger ages.

Since her sons diagnosis, Lapidus helped found the Pitt-Hopkins Syndrome Research Foundation. Having Calvins diagnosis gave us a roadmap of where to start, where to go and whats realistic as far as therapies and treatments, she said. None of that would have been possible without that test.

Next, experts at UCLA are testing the relative merits of broader whole genome sequencing to analyze all 6 billion bases that make up a persons genome. The team is exploring integration of this DNA sequencing with state-of-the-art RNA or gene expression analysis to improve the diagnostic rate.

The entire human genome was first sequenced in 1990 at a cost of $2.7 billion. Today, doctors can perform the same test at a tiny fraction of that cost, and believe that sequencing whole genomes of individuals could vastly improve disease diagnoses and medical care.

See original here:
Life Lessons: Next generation testing - WFMZ Allentown

In this photo provided by Oregon Health & Science University, taken through a microscope, human embryos grow in a laboratory for a few days after researchers used gene editing technology to successfully repair a heart disease-causing genetic mutation. The work, a scientific first led by researchers at Oregon Health & Science University, marks a step toward one day preventing babies from inheriting diseases that run in the family.(Oregon Health & Science University via AP)

By Johnny Kung

Mon., Aug. 21, 2017

Recently, an international team of scientists successfully corrected a disease-causing gene in human embryos, using a gene editing technique called CRISPR. This has led to much excitement about the prospects of curing debilitating diseases in entire family lineages.

At the same time, the possibility of changing embryos genes has renewed fear about designer babies. The hype in both directions should be tempered by the fact that both these scenarios are some ways off a lot more work will need to be done to improve the techniques safety and efficacy before it can be applied in the clinic.

And because a lot of diseases, as well as other physical and behavioural characteristics, are controlled by the complex interaction of many genes with each other and with the environment, in many cases simple genetic fixes may never be possible.

But while the technology is still in early stages, now is the time to have frank, open and societywide conversations about how gene editing should be moving forward and genetic medicine more broadly, including the use of advanced genetic testing and sequencing to diagnose disease, personalize medical treatments, screening babies, etc.

We must raise broad awareness of the health benefits as well as the personal, social and ethical implications of genetics. This is important for individuals both to understand their options when making decisions about their own health care, and to participate as informed citizens in democratic deliberations about whether and how genetic technologies should be developed and applied.

In the U.S., affordability and insurance coverage strongly influence access to genetic medicine. In Canada, the reality of strapped budgets means access is far from equal either. But our public health-care system means it is at least conceivable that these technologies will eventually be available to a higher proportion of people who need them.

For example, OHIP currently pays for genetic testing and counselling for a number of diseases, such as http://www.mountsinai.on.ca/care/mkbc/medical-services/genetic-testingBRCA testingEND for breast and ovarian cancer, for patients who satisfy certain eligibility criteria. It also covers a kind of genetic screening tests called non-invasive prenatal testing (NIPT) for eligible pregnant women. Precisely because of this potential for widespread adoption, there is all the greater need for broad-based conversations about genetics.

Crucially, to ensure that the largest possible cross section of society will benefit from, and not be harmed by, advances in genetic technologies, these conversations must include the voices of all communities.

This is especially true for those who, for well-justified historical reasons, may harbour deep distrust of the biomedical establishment. In the U.S., for much of the 20th century, the eugenics movement had resulted in a range of sterilization programs, discriminatory policies and scientific abuses (such as the infamous Tuskegee syphilis trials) that disproportionately targeted the poor and, especially, racial minorities such as African Americans.

While the eugenics movement might have been less established in Canada, where it did occur (e.g., the sterilization program in Alberta or the Indian hospitals in B.C.) it had most heavily affected Indigenous communities. In both countries, this shameful history has led to lower trust and usage of the health-care system by the affected communities.

As genetic medicine advances, many scientists and health researchers are pointing out the importance of having the diversity of human populations represented in genetic studies in order to gain medical insights that can benefit everyone. If we fail to fully engage these under-represented communities and ensure that genetics is not just another way to exploit and discriminate against them, then we risk worsening this historical and ongoing injustice.

New genetic technologies, such as gene editing, also bring issues of disability rights into sharper focus. While designer babies may not be an immediate concern, even the possibility of selecting and changing our offsprings characteristics raises thorny questions.

For example, what conditions count as medically necessarily to treat how about deafness, dwarfism, autism, or intersex conditions? Ultimately, it is about what kinds of people get to live, and who gets to make those decisions. Many disability rights advocates (e.g., the Down syndrome community) are already voicing concerns about what these emerging technologies mean for how their communities are seen and valued today.

We must make sure that the conversations around genetics are not only about generalized notions of safety or effectiveness, or concerns of playing God. These conversations must also encompass questions of access and justice, and acknowledge that the benefits and harms of genetic technologies, like any new technologies, are not distributed equally.

And these conversations must involve all communities (be they of different racial or ethnic background, gender or sexuality, and physical or cognitive abilities) in a way that ensures their voices are respected and heard.

This is a task that will involve concerted efforts from scientists, funders and industry, to build trust with these communities and to genuinely listen and respond to their concerns. And it will need to be done in collaboration with many partners, including schools, community and faith groups, and the art/entertainment industry.

The ability to understand and, perhaps one day, change our genetics has huge potential to improve human well-being. Lets make sure that everyone will enjoy these benefits, and that no communities are left behind, or worse yet, harmed in the process.

Johnny Kung is the director of new initiatives for the Personal Genetics Education Project (www.pged.org ) at Harvard Medical Schools Department of Genetics.

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Designer babies the not most urgent concern of genetic medicine - Toronto Star

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A comprehensive genomic analysis of Wilms tumor - the most common kidney cancer in children - found genetic mutations involving a large number of genes that fall into two major categories. These categories involve cellular processes that occur early in kidney development. The study, published in Nature Genetics, offers the possibility that targeting these processes, instead of single genes, may provide new opportunities for treatment of Wilms tumor.

"It is very difficult to therapeutically target over 40 genes that may be mutated in Wilms tumor," said senior author Elizabeth Perlman, MD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago. "We discovered that many of these genetic mutations converge into two developmental pathways that lead to cancer. Early development of the kidney starts with rapid proliferation of undifferentiated cells. Within these cells, a signal triggers a switch to undergo differentiation into the normal cells of the kidney. In Wilms tumors, one set of mutations promotes abnormal and continued proliferation of the undifferentiated cells. A second set of mutations impacts the differentiation switch itself. Targeting these two different pathways in future studies might be more efficient than targeting individual gene mutations."

Perlman is the Head of the Department of Pathology and Laboratory Medicine at Lurie Children's and a Professor of Pathology at Northwestern University Feinberg School of Medicine. She is the Arthur C. King Professor of Pathology and Laboratory Medicine.

In the study, Perlman and colleagues in the Children's Oncology Group and the National Cancer Institute initially identified all genetic mutations in 117 Wilms tumor cases. Then they focused on a set of genetic mutations that occurred in more than one case and conducted a targeted analysis of these recurrent mutations in 651 Wilms tumors to validate the results. They found that the most common genes mutated in Wilms tumor were TP53, CTNNB1, DROSHA, WT1 and FAM123B.

In an unexpected finding, Perlman and colleagues also identified underlying germline mutations - or mutations in all the cells of the body - in at least 10 percent of Wilms tumor cases. "Our discovery of germline mutations in so many cases of Wilms tumor means that the children and family members of these patients may be at risk for tumor development," said Perlman.

Explore further: Researchers find new gene mutations for Wilms Tumor

More information: A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nature Genetics (2017). DOI: 10.1038/ng.3940

Journal reference: Nature Genetics

Provided by: Ann & Robert H. Lurie Children's Hospital of Chicago

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Comprehensive genomic analysis offers insights into causes of Wilms tumor development - Medical Xpress

We all have about 24,000 genes. How those genes are structured and interact can determine our current health and our future health.

Modern medicine includes specialists in this field called Clinical Geneticists. In todays TPR Lifeline, Bioscience-Medicine reporter Wendy Rigby talks to Baylor College of Medicines Scott McLean, MD, about his work at the Childrens Hospital of San Antonio.

Rigby: Dr. McLean, what is clinical genetics?

McLean: Clinical genetics is the medical specialty that uses genetic information to improve your genetic health or to understand the basis for a variety of medical conditions.

Those of us who have had children in Texas know that while youre still in the hospital, you get some genetic testing done. What is that called and what are you looking for?

We have newborn screening which is actually a blood test that is given to all babies 24 and 48 hours of age. The blood test involves collecting that blood on a piece of paper, filter paper, and sending that to the Texas State Department of Health Services in Austin where they do a series of tests.

This is the foot prick?

This is where you prick the heel. It seem awfully cruel. Babies cry. Parents dont like it. But its actually a wonderful test because it allows us to screen for over 50 conditions.

Give us some examples. What are some of the genetic conditions we might have heard of?

Well, the initial condition that was screened for in newborn screening in the United States was PKU which stands for Phenylketonuria. This is a condition that results in intellectual disability and seizures. We can change that outcome if we are able to identify the condition early enough and change the diet.

Lets say a child comes in to Childrens Hospital of San Antonio. Doctors are having trouble figuring out whats going on. Are you called in to consult?

Most of our patients that we see in the outpatient clinic are sent to us by consultation from physicians in the community or from nurseries, neonatal intensive care units. They range from situations such as multiple birth defects, to autism, intellectual disability, seizures, encephalopathy, blindness, deafness. Theres a whole gamut of reasons that folks come to see us.

When these children become grownups, does that information that youve learned about them help them out if theyre planning to have their own children in the future?

So when pediatric patients make the transition from pediatric care to adult care, its very common for information and ideas to get lost. And we certainly would hope that people remember that. Sometimes when we have identified a situation in a little baby, I tell the parents that I want them to put a sticky note on the last page of their baby book so that when they are showing the baby book to their childs fiance and they get to the last page, it reminds them you need to go back to see the geneticist because theres this genetic situation that you need to have a nice long chat about so that you can plan your family as carefully as possible.

Right. So the work youre doing today could help someone 30 years in the future.

Well, genetics is a very unique specialty in that regard because when we see a patient were not thinking about their next year of life or their next two years of life or the next month. We do think about that. But this is a lifelong diagnosis and a lifelong situation. So I often joke with my patients that Im going to try to put them on the 90-year plan. What we figure out now about their genetics is going to be helpful for them throughout their entire lifespan, at least up until 90 years. And then after that theyre on their own. But well get them to 90.

So its an exciting time to be in the field.

Very exciting. I think the era of gene therapy which for many people we thought was never going to happen, its very promising because we have new technologies that I think are going to allow for advances in that area.

Dr. Scott McLean with Baylor College of Medicine and the Childrens Hospital of San Antonio, thanks for the information.

Youre quite welcome.

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TPR Lifeline: Clinical Genetics Is A Growing Field - Texas Public Radio