StemCell Therapy

A friend of mine with Central American, Southern European, and West African ancestry islactose intolerant. Drinking milk products upsets her stomach, and so she avoids them. About a decade ago, because of her low dairy intake, she feared that she might not be getting enough calcium, so she asked her doctor for abone density test. He responded that she didnt need one because blacks do not get osteoporosis.

My friend is not alone. The view that black people dont need a bone density test is a longstanding and common myth. A2006 studyin North Carolina found that out of 531 African American and Euro-American women screened for bone mineral density, only 15 percent were African American womendespite the fact that African American women made up almost half of that clinical population. A health fair in Albany, New York, in 2000,turned into a ruckuswhen black women were refused free osteoporosis screening. The situationhasnt changed muchin more recent years.

Meanwhile,FRAX, a widely used calculatorthat estimates ones risk of osteoporotic fractures, is based on bone density combined with age, sex, and, yes, race. Race, even though it is never defined or demarcated, is baked into the fracture risk algorithms.

Lets break down the problem.

First, presumably based on appearances, doctors placed my friend and others into a socially defined race box called black, which is a tenuous way to classify anyone.

Race is a highly flexible way in which societies lump people into groups based on appearance that is assumed to be indicative of deeper biological or cultural connections. As a cultural category, the definitions and descriptions of races vary. Color lines based on skin tone can shift, which makes sense, but the categories are problematic for making any sort of scientific pronouncements.

Second, these medical professionals assumed that there was a firm genetic basis behind this racial classification, which there isnt.

Third, they assumed that this purported racially defined genetic difference would protect these women from osteoporosis and fractures.

Some studies suggestthat African American womenmeaning women whose ancestry ties back to Africamay indeed reach greater bone density than other women, which could be protective against osteoporosis. But that does not mean being blackthat is, possessing an outward appearance that is socially defined as blackprevents someone from getting osteoporosis or bone fractures. Indeed, this same research also reports that African American women are more likely to die after a hip fracture. The link between osteoporosis risk and certain racial populations may be due to lived differencessuch as nutritionandactivity levels, both of which affect bone density.

But more important:Geographicancestry is not the same thing as race. African ancestry, for instance, does not tidily map onto being black (or vice versa). In fact, a2016 studyfound wide variation in osteoporosis risk among women living in different regions within Africa. Their genetic risks have nothing to do with their socially defined race.

When medical professionals or researchers look for ageneticcorrelateto race, they are falling into a trap: They assume thatgeographic ancestry, which does indeed matter to genetics, can be conflated with race, which does not. Sure, different human populations living in distinct places may statistically have different genetic traitssuch as sickle cell trait (discussed below)but such variation is aboutlocal populations(people in a specific region), not race.

Like a fish in water, weve all been engulfed by the smog of thinking that race is biologically real. Thus, it is easy to incorrectly conclude that racial differences in health, wealth, and all manner of other outcomes are the inescapable result of genetic differences.

The reality is that socially defined racial groups in the U.S. and most everywhere else do differ in outcomes. But thats not due to genes. Rather, it is due to systemic differences in lived experience and institutional racism.

Communities of color in the United States, for example, often have reduced access to medical care, well-balanced diets, andhealthy environments. They are often treated more harshly in their interactions withlaw enforcement and the legal system. Studies show that they experience greater social stress, includingendemic racism, that adversely affects all aspects of health. For example, babies born to African American women are more thantwice as likely to diein their first year than babies born to non-Hispanic Euro-American women.

Systemic racism leads to different health outcomes for various populations. The infant mortality rate, for example, for African American infants is double that for European Americans. (Credit: Kelly Lacy/Pexels)

As a professor of biological anthropology, I teach and advise college undergraduates. While my students are aware of inequalities in the life experiences of different socially delineated racial groups, most of them also think that biological races are real things. Indeed, more than half of Americans still believe that their racial identity is determined byinformation contained in their DNA.

For the longest time, Europeans thought that the sun revolved around the Earth. Their culturally attuned eyes saw this as obvious and unquestionably true. Just as astronomers now know thats not true,nearly all population geneticistsknow that dividing people into races neither explains nor describes human genetic variation.

Yet this idea of race-as-genetics will not die. For decades, it has been exposed to the sunlight of facts, but, like a vampire, it continues to suck bloodnot only surviving but causing harm in how it can twist science to support racist ideologies. With apologies for the grisly metaphor, it is time to put a wooden stake through the heart of race-as-genetics. Doing so will make for better science and a fairer society.

In 1619, the first people from Africa arrived in Virginia and became integrated into society. Only after African and European bond laborers unified in various rebellions did colony leaders recognize the need to separate laborers.Race dividedindentured Irish and other Europeans from enslaved Africans, and reduced opposition by those of European descent to the intolerable conditions of enslavement. What made race different from other prejudices, including ethnocentrism (the idea that a given culture is superior), is that it claimed that differences were natural, unchanging, and God-given. Eventually, race also received the stamp of science.

Over the next decades, Euro-American natural scientists debated the details of race, asking questions such as how often the races were created (once, as stated in the Bible, or many separate times), the number of races, and their defining, essential characteristics. But they did not question whether races were natural things. They reified race, making the idea of race real by unquestioning, constant use.

In the 1700s, Carl Linnaeus, the father of modern taxonomy and someone not without ego, liked to imagine himself asorganizing what God created. Linnaeus famously classified ourown species into racesbased on reports from explorers and conquerors.

The race categories he created includedAmericanus,Africanus, and evenMonstrosus(for wild and feral individuals and those with birth defects), and their essential defining traits included a biocultural mlange of color, personality, and modes of governance. Linnaeus describedEuropeausas white, sanguine, and governed by law, andAsiaticusas yellow, melancholic, and ruled by opinion. These descriptions highlight just how much ideas of race are formulated by social ideas of the time.

Swedish taxonomist Carl Linnaeus divided humanity up into racial categories according to his notion of shared essences among populations, a concept researchers now recognize has no scientific basis. (Credit: Wikimedia Commons/Public Domain)

In line with early Christian notions, these racial types were arranged in a hierarchy:a great chain of being, from lower forms to higher forms that are closer to God. Europeans occupied the highest rungs, and other races were below, just above apes and monkeys.

So, the first big problems with the idea of race are that members of a racial group do not share essences, Linnaeus idea of some underlying spirit that unified groups, nor are races hierarchically arranged. A related fundamental flaw is that races were seen to be static and unchanging. There is no allowance for a process of change or what we now call evolution.

There have been lots of efforts since Charles Darwins time to fashion the typological and static concept of race into an evolutionary concept. For example, Carleton Coon, a former president of the American Association of Physical Anthropologists, argued inThe Origin of Races(1962) that five racesevolved separatelyand became modern humans at different times.

One nontrivial problem with Coons theory, and all attempts to make race into an evolutionary unit, is that there is no evidence. Rather, all the archaeological and genetic data point to abundant flows of individuals, ideas, and genes across continents, withmodern humansevolving at the same time, together.

Afew pundits such asCharles Murrayof the American Enterprise Institute and science writers such asNicholas Wade, formerly ofThe New York Times, still argue that even though humans dont come in fixed, color-coded races, dividing us into races still does a decent job ofdescribinghuman genetic variation. Their position is shockingly wrong. Weve known for almost 50 years that race does not describe human genetic variation.

In 1972, Harvard evolutionary biologist Richard Lewontinhad the idea to testhow much human genetic variation could be attributed to racial groupings. He famously assembled genetic data from around the globe and calculated how much variation was statistically apportioned within versus among races. Lewontin found that only about 6 percent of genetic variation in humans could be statistically attributed to race categorizations. Lewontin showed that the social category of race explains very little of the genetic diversity among us.

Furthermore, recent studies reveal that the variation between any two individuals isverysmall, on the order of onesingle nucleotide polymorphism(SNP), or single letter change in our DNA, per 1,000. That means that racial categorization could, at most, relate to 6 percent of the variation found in 1 in 1,000 SNPs. Put simply, race fails to explain much.

In addition, genetic variation can be greaterwithingroups that societies lump together as one race than it is between races. To understand how that can be true, first imagine six individuals: two each from the continents of Africa, Asia, and Europe. Again, all of these individuals will be remarkably the same: On average, only about 1 out of 1,000 of their DNA letters will be different. A study by Ning Yu and colleaguesplaces the overall differencemore precisely at 0.88 per 1,000.

The researchers further found that people in Africa had less in common with one another than they did with people in Asia or Europe. Lets repeat that: On average, two individuals in Africa aremoregenetically dissimilar from each other than either one of them is from an individual in Europe or Asia.

Homo sapiensevolved in Africa; the groups that migrated out likely did not include all of the genetic variation that built up in Africa. Thats an example of what evolutionary biologists call thefounder effect, where migrant populations who settle in a new region have less variation than the population where they came from.

Genetic variation across Europe and Asia, and the Americas and Australia, is essentially a subset of the genetic variation in Africa. If genetic variation were a set of Russian nesting dolls, all of the other continental dolls pretty much fit into the African doll.

What all these data show is that the variation that scientistsfrom Linnaeus to Coon to the contemporary osteoporosis researcherthink is race is actually much better explained by a populationslocation. Genetic variation is highly correlated togeographic distance. Ultimately, the farther apart groups of people are from one another geographically, and, secondly, the longer they have been apart, can together explain groups genetic distinctions from one another. Compared to race, those factors not only better describe human variation, they invoke evolutionary processes to explain variation.

Those osteoporosis doctors might argue that even though socially defined race poorly describes human variation, it still could be a useful classification tool in medicine and other endeavors. When the rubber of actual practice hits the road, is race a useful way to make approximations about human variation?

When Ive lectured at medical schools, my most commonly asked question concerns sickle cell trait. Writer Sherman Alexie, a member of the Spokane-Coeur dAlene tribes, put the question this wayin a 1998 interview: If race is not real, explain sickle cell anemia to me.

OK! Sickle cell is a genetic trait: It is the result of an SNP that changes the amino acid sequence of hemoglobin, the protein that carries oxygen in red blood cells. When someone carries two copies of the sickle cell variant, they will have the disease. In the United States, sickle cell disease is most prevalent in people who identify as African American, creating the impression that it is a black disease.

(Credit: SciePro/Shutterstock)

Yet scientists have known about the much more complexgeographic distributionof sickle cell mutation since the 1950s. It is almost nonexistent in the Americas, most parts of Europe and Asiaand also in large swaths of Northern and Southern Africa. On the other hand, it is common in West-Central Africa and also parts of the Mediterranean, Arabian Peninsula, and India. Globally, it does not correlate with continents or socially defined races.

Inone of the most widely citedpapers in anthropology, American biological anthropologist Frank Livingstone helped to explain the evolution of sickle cell. He showed that places with a long history of agriculture and endemic malaria have a high prevalence of sickle cell trait (a single copy of the allele). He put this information together with experimental and clinical studies that showed how sickle cell trait helped people resist malaria, and made a compelling case for sickle cell trait being selected for in those areas.Evolution and geography, not race, explain sickle cell anemia.

What about forensic scientists: Are they good at identifying race? In the U.S., forensic anthropologists are typically employed by law enforcement agencies to help identify skeletons, including inferences about sex, age, height, and race. The methodological gold standards for estimating race are algorithms based on a series of skull measurements, such as widest breadth and facial height. Forensic anthropologists assume thesealgorithms work.

The origin of the claim that forensic scientists are good at ascertaining race comes from a 1962 study of black, white, and Native American skulls, which claimed an 8090 percent success rate. That forensic scientists are good at telling race from a skull is a standard trope of both thescientific literatureandpopular portrayals.But my analysisof four later tests showed that the correct classification of Native American skulls from other contexts and locations averaged about two incorrect for every correct identification. The results are no better than a random assignment of race.

Thats because humans are not divisible into biological races. On top of that, human variation does not stand still. Race groups are impossible to define in any stable or universal way. It cannot be done based on biologynot by skin color, bone measurements, or genetics. It cannot be done culturally: Race groupings have changed over time and place throughout history.

Science 101: If you cannot define groups consistently, then you cannot make scientific generalizations about them.

Skull measurements are a longstanding tool in forensic anthropology. (Credit: Internet Archive Book Images/Flickr/Public Domain)

Wherever one looks, race-as-genetics is bad science. Moreover, when society continues to chase genetic explanations, it misses the larger societal causes underlying racial inequalities in health, wealth, and opportunity.

To be clear, what I am saying is that human biogenetic variation is real. Lets just continue to study human genetic variation free of the utterly constraining idea of race. When researchers want to discuss genetic ancestry or biological risks experienced by people in certain locations, they can do so without conflating these human groupings withracial categories. Lets be clear that genetic variation is an amazingly complex result of evolution and mustnt ever be reduced to race.

Similarly, race is real, it just isnt genetic. Its a culturally created phenomenon. We ought to know much more about the process of assigning individuals to a race group, including the category white. And we especially need to know more about the effects of living in a racialized world: for example, how a societys categoriesand prejudiceslead to health inequalities. Lets be clear that race is a purely sociopolitical construction with powerful consequences.

It is hard to convince people of the dangers of thinking race is based on genetic differences. Like climate change, the structure of human genetic variation isnt something we can see and touch, so it is hard to comprehend. And our culturally trained eyes play a trick on us by seeming to see race as obviously real. Race-as-genetics is even more deeply ideologically embedded than humanitys reliance on fossil fuels and consumerism. For these reasons, racial ideas will prove hard to shift, but it is possible.

Over 13,000 scientistshave come together to formand publicizea consensus statement about the climate crisis, and that has surely moved public opinion to align with science. Geneticists and anthropologists need to do the same for race-as-genetics. The recent American Association of Physical AnthropologistsStatement on Race & Racismis a fantastic start.

In the U.S., slavery ended over 150 years ago and the Civil Rights Law of 1964 passed half a century ago, but the ideology of race-as-genetics remains. It is time to throw race-as-genetics on the scrapheap of ideas that are no longer useful.

We can start by getting my friendand anyone else who has been deniedthat long-overdue bone density test.

Alan Goodmanis a professor of biological anthropology at Hampshire College in Massachusetts. This story was originally posted onSAPIENS. Read the original articlehere.

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Race Is Real, But It's Not Genetic - Discover Magazine

The combined company will be poised to transform care for cancer patients, accelerating adoption of genetics through the most comprehensive suite of products and services available. Integrating germline testing, tumor profiling and liquid biopsy technologies and services in a single platform will enable precision approaches from diagnostic testing to therapy optimization and monitoring, expanding access to best-in-class personalized oncology.

"From the beginning, Invitae's goal has been to aggregate the world's genetic tests into a single platform in service of our mission to bring comprehensive genetic information into mainstream medicine. Today, we take another major step forward in that effort," said Sean George, Ph.D., co-founder and chief executive officer of Invitae.

"ArcherDXand Invitae share a foundational belief in the power of genomic information toimpact care. We are thrilled to unite with Invitae to form the leading hub for precision oncology, diagnostics, therapy optimization and monitoring, with an opportunity to accelerate both patient care and shareholder value," said Jason Myers, Ph.D., chief executive officer and co-founder of ArcherDX. "ArcherDXwas founded to democratize precision oncology with best-in-class products that are personal, actionable and available in local care settings. We see STRATAFIDE DX as a significant near-term value driver, currently under development for cancer therapy optimization, while PCM provides an exciting opportunity to transform cancer care through multiple monitoring applications. ArcherDXproducts, workflow and powerful bioinformatics solutions provide an opportunity to advance precision oncology into regional and community settings and address an estimated $45 billion market opportunity. Together with Invitae, we look forward to expanding our impact beyond oncology, driving significant value through shared expertise to inform healthcare throughout life, globally."

"Integrating all aspects of cancer genetics can transform care for patients and the flexibility that comes from both centralized and decentralized capabilities will uniquely position Invitae to meet the needs of customers worldwide," continued Dr. George. "By joining together, we will unite world-class capabilities in the hands of a talented team with complementary expertise and strong brands in service of a shared goal to improve healthcare for patients."

Accelerating access and adoption of genetics to improve cancer care

Broad adoption of precision oncology has been limited, particularly in regional and community settings where approximately 85 percent of patients receive care.1 Without precision oncology, late-stage cancer patients can suffer from poor prognosis and outcomes, while early-stage patients may receive an inaccurate prognosis that results in unnecessary treatment and delayed detection of recurrence.2,3

Uniting Invitae and ArcherDXwill offer comprehensive support for precision oncology.

With both centralized and local testing capabilities, the combined organization will offer breadth and flexibility in serving customers in more than 95 markets. Together, Invitae and ArcherDXwill offer robust support for biopharmaceutical companies, from patient identification and screening, to biomarker identification and companion diagnostic development.

Transaction Terms

Under the terms of the agreement, Invitae will acquire ArcherDXfor upfront consideration consisting of 30 million shares of Invitae common stock and $325 million in cash, plus up to an additional 27 million shares of Invitae common stock payable in connection with the achievement of certain milestones, for an overall transaction valued at approximately $1.4 billion. The transaction, which has been unanimously approved by the Boards of Directors of both companies, is expected to close in several months, subject to customary closing conditions including approval by the stockholders of Invitae and ArcherDX.

Financing Activities

In connection with the proposed combination, Invitae has arranged a strategic financing with over $400 million in financing commitments from a premier syndicate of life sciences investors, led by Perceptive Advisors. Invitae has entered into a definitive agreement to sell $275 million in common stock in a private placement at a price of $16.85 per share. The private placement is being supported by key existing investors in Invitae and Archer, including Casdin Capital, Deerfield Management, Driehaus Capital Management, Farallon, PBM Capital, Perceptive Advisors, Redmile Group, Rock Springs Capital, Soleus Capital, and one additional institutional investor. The placement is expected to close concurrently with the proposed combination, subject to the satisfaction of customary closing conditions. Invitae has also entered into a fully committed credit facility for up to $200 million with Perceptive Credit Opportunities Funds, subject to certain customary closing conditions.

Since the filing of its Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, Invitae has sold under its ATM facility approximately 2.6 million shares of common stock for aggregate gross proceeds of $46 million at an average price of $17.59 per share.

Invitae's current expectations regarding its cash at transaction close would be approximately $425 million and its annualized near-term forward cash burn is expected to be approximately $130 million.

Advisors

Perella Weinberg Partners served as lead financial advisor to Invitae in connection with the business combination and Cowen served as co-financial advisor. Cowen served as lead-placement agent to Invitae for the private placement and Perella Weinberg Partners served as co-placement agent; Cowen served as exclusive financial advisor to Invitae in connection with the senior secured term loan facility. Evercore and J.P. Morgan Securities LLC acted as financial advisors to Archer.

Webcast

Management will host a conference call and webcast today at 5:00 a.m. PT / 6:00 a.m. MT / 8:00 a.m. ET to discuss the transaction. The dial-in numbers for the conference call are (866) 324-3683 for domestic callers and (509) 844-0959 for international callers, and the reservation number for both is 7097864. Please note, after dialing in, you will be prompted to enter the Conference ID and then the pound "#" sign to enter the call. Following prepared remarks, management will respond to questions from analysts, subject to time limitations.

The live webcast of the call and slide deck may be accessed by visiting the investors section of the company's website atir.invitae.com.A replay of the webcast and conference call will be available shortly after the conclusion of the call and will be archived on the company's website.

About Invitae

Invitae Corporation(NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website atinvitae.com.

About ArcherDX

ArcherDX is a leading genomic analysis company democratizing precision oncology through a suite of products and services that are highly accurate, personal, actionable and easy to use in local settings. Our ArcherDXplatform, with our proprietary Anchored Multiplex PCR (AMP) chemistry at the core, has enabled us to develop industry-leading products and services with the goal to optimize therapy and enable cancer monitoring across sample types. We develop and commercialize research products, are developing in vitro diagnostic (IVD) products, and offer services that meet the unique needs of our customers and their clinical applications. Our research product portfolio consists of VariantPlex, FusionPlex, LiquidPlex and Immunoverse, which we collectively refer to as ArcherPlex. IVD products currently in development for solid tumor biomarker identification and Personalized Cancer Monitoring (PCM) have both received Breakthrough Device Designation from the FDA. ArcherDXis headquartered in Boulder, Colorado. Learn more at http://www.archerdx.comand follow @ArcherDXIncon Twitter, Facebookand LinkedIn.

Safe Harbor Statement

This press release contains statements, including statements regarding the proposed acquisition of ArcherDX, Inc. ("Archer") by Invitae Corporation ("Invitae") that are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that are intended to be covered by the "safe harbor" created by those sections. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, expectations and events, can generally be identified by the use of forward-looking terms such as "believe," "expect," "may," "will," "should," "would," "could," "seek," "intend," "plan," "goal," "project," "estimate," "anticipate" or other comparable terms. All statements other than statements of historical facts included in this presentation regarding strategies, synergies, prospects, financial results, operations, costs, plans, objectives, and the proposed acquisition of Archer by Invitae are forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding expected future operating results, including cash at closing and annualized forward cash burn, drivers of future value, future products and services and customers served, regulatory submissions, anticipated results of product development efforts, potential addressable markets, the impact of Covid-19, the anticipated benefits of the proposed acquisition of Archer, including expected synergies, opportunities, product offerings, and financial and other impacts, the transaction structure and financing plans, and the expected timing of completion of the proposed transaction. Forward-looking statements are neither historical facts nor assurances of future performance or events. Instead, they are based only on current beliefs, expectations and assumptions regarding future business developments, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Forward-looking statements are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Actual results, conditions and events may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause actual results, conditions and events to differ materially from those indicated in the forward-looking statements include, but are not limited to: the ability to successfully and profitably market our products and services; the acceptance of our products and services by patients and healthcare providers; the ability to meet demand for our products and services; the availability and sufficiency of reimbursement; the amount and nature of competition; the effects of the adoption, modification or repeal of any law, rule, order, interpretation or policy relating to the healthcare system, including without limitation as a result of any judicial, executive or legislative action; the impact of Covid-19 on the business of Invitae and Archer; Invitae's ability to manage its growth effectively; the ability of Invitae and Archer to successfully develop new products and services; the ability to effectively utilize strategic partnerships and acquisitions; the ability of Invitae and Archer to obtain and maintain regulatory approvals and comply with applicable regulations; the ability of Invitae and Archer to obtain the required regulatory approvals for the proposed merger and the approval of Invitae's and Archer's stockholders, and to satisfy the other conditions to the closing of the acquisition and related financing transactions on a timely basis or at all; the occurrence of events that may give rise to a right of one or both of Invitae and Archer to terminate the merger agreement; negative effects of the announcement or the consummation of the acquisition on the market price of Invitae's common stock and/or on the companies' respective businesses, financial conditions, results of operations and financial performance; significant transaction costs and/or unknown liabilities; the possibility that the anticipated benefits from the proposed acquisition of Archer cannot be realized in full or at all or may take longer to realize than expected; risks associated with contracts containing consent and/or other provisions that may be triggered by the proposed acquisition of Archer; risks associated with transaction-related litigation; the possibility that costs or difficulties related to the integration of Archer's operations with those of Invitae will be greater than expected; the ability of companies individually and the combined company to retain and hire key personnel; Invitae's failure to manage growth effectively; Invitae's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; Invitae's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to Invitae's business, and the risks and uncertainties set forth in Invitae's reports on Forms 10-K, 10-Q and 8-K filed with or furnished to the Securities and Exchange Commission (the "SEC") and other written statements made by Invitae from time to time. There can be no assurance that the proposed acquisition of Archer will in fact be consummated in the manner described or at all. Forward -looking statements speak only as of the date hereof, and Invitae disclaims any obligation to update any forward-looking statements.

NOTE: Invitae and the Invitae logo are trademarks of Invitae Corporation. All other trademarks and service marks are the property of their respective owners.

Additional Information and Where to Find It

In connection with the proposed transaction, Invitae will file with the SEC a registration statement on Form S-4, which will include a document that serves as a proxy statement/prospectus of Invitae (the "proxy statement/prospectus"), and will file other documents regarding the proposed transaction with the SEC. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ THE REGISTRATION STATEMENT, PROXY STATEMENT/PROSPECTUS AND OTHER RELEVANT DOCUMENTS FILED WITH THE SEC WHEN THEY BECOME AVAILABLE, BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION. A definitive proxy statement/prospectus will be sent to Invitae's stockholders when it becomes available. Investors and security holders will be able to obtain the registration statement and the proxy statement/prospectus free of charge from the SEC's website or from Invitae when it becomes available. The documents filed by Invitae with the SEC may be obtained free of charge at Invitae's website at http://www.invitae.com or at the SEC's website at http://www.sec.gov. These documents may also be obtained free of charge from Invitae by requesting them by mail at Invitae Corporation, 1400 16th Street, San Francisco, California 94103, or by telephone at (415) 374-7782.

Participants in the Solicitation

Invitae and its directors and executive officers and other members of management and employees may be deemed to be participants in the solicitation of proxies in connection with the proposed transaction. Information about Invitae's directors and executive officers is available in Invitae's proxy statement dated April 29, 2020 for its 2020 Annual Meeting of Stockholders. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the registration statement, the proxy statement/prospectus and other relevant materials to be filed with the SEC regarding the proposed transaction when they become available. Stockholders, potential investors and other readers should read the proxy statement/prospectus carefully when it becomes available before making any voting or investment decisions. You may obtain free copies of these documents from Invitae as indicated above.

No Offer or Solicitation

This communication shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act of 1933, as amended.

Non-GAAP Financial Measures

Cash burn is a non-GAAP measure, is not based on any standardized methodology prescribed by GAAP and is not necessarily comparable to similarly-titled measures presented by other companies. A limitation of using cash burn is that it does not represent the total change in cash, cash equivalents, and restricted cash for a period because it excludes cash provided by or used for other operating, investing or financing activities. Management accounts for this limitation by providing information about Invitae's historical operating, investing and financing activities in the statements of cash flows in the consolidated financial statements in its most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K and by presenting net cash provided by (used in) operating, investing and financing activities as well as the net increase or decrease in cash, cash equivalents and restricted cash in its reconciliation of cash burn with such financial statements.

Cash burn is calculated as net increase or decrease in cash and cash equivalents and restricted cash less (a) changes in marketable securities, (b) cash received from equity and debt financings, (c) cash received from exercises of warrants, (d) cash payments made for business acquisitions, and (e) changes in unrealized gains and losses on marketable securities. A reconciliation to GAAP has not been provided as the reconciliation could not reasonably be estimated.

Contact for Invitae:Laura D'Angelo[emailprotected](628) 213-3369

Contact for ArcherDX:Andrea N. Flynn, Ph.D.Investor Relations & Corporate Communications[emailprotected]

1El-Deiry, W., et al. The current state of molecular testing in the treatment of patients with solid tumors, 2019. Cancer J Clin. 2019;69(4): 305-3432Hyman DM, et al. Implementing Genome-Driven Oncology. Cell. 2017;168(4):5845993Benayed, R, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res. April 2019.

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Invitae and ArcherDX to create a global leader in comprehensive cancer genetics and precision oncology - PRNewswire

Factors such as age and underlying health conditions such as diabetes can put you at a higher risk of contracting coronavirus, according to the U.S. Centers for Disease Control and Prevention. But one more factor that could affect your chances of getting coronavirus is your blood type, at least according to one recent study.

People who have blood Type A were associated with a 45% higher risk of acquiring COVID-19 compared to people with other blood types, according to a study published Wednesday in the peer-reviewed New England Journal of Medicine by a team of European scientists. Meanwhile, people with blood Type O, the most common blood type, less likely to get coronavirus as people with other blood types.

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The researchers arrived at this result after performing genetic analysis on more than 1,900 severely ill coronavirus patients in Spain and Italy and comparing them with over 2,000 patients who were not sick.

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A commonality they found was a DNA cluster which determines blood types, among other components within the human body. This prompted further research into which specific blood types were present in the majority of the severe cases of coronavirus they looked at.

Because the DNA cluster is found in other parts of the body, it may not be the case that blood type can predict ones risk of contracting coronavirus, said Roy Silverstein, a hematologist who is the chairman of the department of medicine at the Medical College of Wisconsin.

Those who are not Type A should not interpret this study to mean that they can let their guard down. Similarly, the data are not yet convincing enough to recommend that those with Type A need to do even more than what is recommended.

Those who are not type A should not interpret this study to mean that they can let their guard down, Silverstein, former president the American Society of Hematology, said. Similarly, the data are not yet convincing enough to recommend that those with Type A need to do even more than what is recommended.

Everyone needs to pay attention to COVID-19 prevention by following well-accepted guidelines related to social distancing, face covering, hand-washing, and self-isolation and testing in the setting of possible COVID-related symptoms.

A prior study published by the Southern University of Science and Technology in China, which has not been peer-reviewed, and a study by 23andMe, a privately held genetic-analysis company, pointed to similar results.

But even still, Silverstein urged people to take these findings with a grain of salt.

This study, along with other studies from China and from 23andMe all suggest, but do not prove, a statistical association between non-O blood type with either risk of infection with the COVID-19 virus, or with risk of developing severe disease if infected.

But the studies, he said, should prompt more rigorous clinical studies as well as basic science studies to probe the mechanisms by which ABO blood type and or ABO genes might influence coronavirus ability to infect cells or the bodys immune response to the virus.

More:
Blood type and genetics may determine your odds of contracting the coronavirus, study finds - MarketWatch

LUBBOCK, Texas (NEWS RELEASE) The following is a news release from Texas Tech University:

Think of the last time you had a cut on your leg or foot. How long did it take for that wound to show signs of healing? If it was longer than three weeks, doctors would refer to it as a chronic wound. These types of non-healing wounds affect millions of people and are often associated with other chronic diseases or conditions like diabetes, decreased circulation and neuropathy.

But now, in a first-of-its-kind study, researchers have determined that genetics may play a role in how wounds heal.Caleb Phillips, an assistant professor at Texas Tech University and director of thePhillips Laboratoryin theDepartment of Biological Sciences, anddoctoral studentCraig Tipton led the study, Patient genetics is linked to chronic wound microbiome composition and healing, published Thursday (June 18) in the open-access, peer-reviewed medical journalPLOS Pathogens.

Phillips, who also serves as the Curator of Genetic Resources at theNatural Science Research Laboratorys (NSRL)Robert J. Baker Genetic Resources Collection, said the study determined that certain genes are associated with the number of bacteria and abundance of common pathogens in wounds. The collection of microbes, known as a microbiome, can determine how a wound heals and how long that process takes. The research also showed that the more diversity within a wound microbiome, the less time it took to heal.

A chronic wound is a serious burden, Phillips said. The median healing time of patients in this study was more than 200 days, but some people deal with these wounds for years. We were able to show that a persons genetics explain differences in the species that infect their wounds. The information in this study could be valuable in a clinical setting as pre-operative information to help inform preventative measures before a procedure, as some chronic wounds arise as non-healing surgical wounds, and could help inform a course of treatment for an existing infection.

Researchers included colleagues from Texas Tech, theTexas Tech University Health Sciences Center(TTUHSC), LubbocksSouthwest Regional Wound Care Center(SWRWCC) and the University of North Texas Health Science Center at Fort Worth (UNTHSC). Phillips said the project began after a conversation with Dr. Randy Wolcott, founder of the SWRWCC, where they discussed how certain patients develop multiple non-healing wounds over a long period. The microbiome within each wound was essentially the same. The researchers wanted to find out if this could be partially explained by genetics.

This study is big, Wolcott said. Its the initial study to find genes and/or gene alterations that correlate with what bacterial species can be more successful in causing infections in a specific patient. If a screen of a patients DNA prior to a surgery showed that patient is highly susceptible to a staphylococcus species, the doctor could mitigate staphylococcus complications.

Patients visiting the SWRWCC for the care of a lower-extremity infected wound consented to participation in the study and provided samples from their wound(s) and from a cheek swab. Samples like those collected at the SWRWCC are archived in liquid nitrogen at the Wolcott Wound Care Research Collection, a collection of the NSRLs Genetic Resources Collection that is specifically dedicated to wound care biology. The design of the study included an exploratory cohort of 79 patients, from which candidate locations of their genome were identified. This was followed by an experimental cohort of 85 patients, used to confirm associations between the genomic locations and wound microbiome characteristics.

The bacterial communities infecting an individuals wounds were determined by microbiome sequencing methods, and each patients genome was characterized at a few hundred thousand specific locations, called single nucleotide polymorphisms, or SNPs. A statistical approach was then used to determine which of these genomic locations explained differences in an individuals wound microbiome composition and was followed with several downstream analyses to understand the results.

We showed that there are identifiable locations in peoples genome where, depending on their genotype, they tend to get infections by specific bacteria, Phillips said. The different genomic locations identified tend to be related in terms of the types of genes they are close to and may regulate. A working hypothesis emerging from the research is that genetic differences influencing genes encoding the way our cells interact with the environment and each other are important for infection differences.

Tipton, who completed his bachelors degree in biology atAngelo State Universitybefore arriving at Texas Tech, said the project has been a significant part of his dissertation, which focuses on learning more about why a persons wounds are infected by different types of microbes. Though there is still work to be done before the research directly benefits patients, Tipton said the study is an important and promising step in that direction.

Personalized medicine is a current hot topic in modern healthcare, where the goal is to identify inherent differences within individuals that may cause them to be impacted differently by disease and finding treatments that are well-suited and tailored to the individual and may contribute to better patient outcomes, Tipton said. Our project furthers two equally-interesting avenues of research with potential translation to the clinic. In one, it is our goal to develop robust genomic predictive models that could help physicians to determine a patients risk for chronic wound infection, particularly to specific bacteria.

In the second, this work helps to inform how genetic variation in patients can influence microbiome-host interactions and wound infection pathogenesis. By further studying infection pathogenesis and how these complex microbial communities interact, it may be possible to improve existing therapies or to develop new therapeutic strategies altogether.

Phillips said he looks forward to continuing his research at Texas Tech. His lab is developing a follow-up study that he hopes will collect enough information to create accurate predictive models. They also are working on a study exploring how a persons location in the U.S. shapes differences in chronic wound microbiomes.

Texas Tech provides good support for research and is continually working for growth, Phillips said. My research, like that of most others, has been generally enhanced by the academic freedom provided at the university. The Natural Science Research Laboratory is a premier Natural History Collection, and the samples archived at the Genetic Resources Collection have allowed me to design studies such as this one that would otherwise not have been possible. The hard work and creativity of doctoral student Craig Tipton were essential to the success of this project, as was collaboration with the laboratories ofNicole Phillipsat UNTHSC andKendra Rumbaughat TTUHSC, ProfessorTodd Littlein the Texas TechCollege of Education, the SWRWCC and the NSRL.

The team of researchers included:

To read the complete study, visit the PLOS Pathogens website.

(News release from Texas Tech University)

Original post:
Researchers say genetics may determine wound infection and healing - KLBK | KAMC | EverythingLubbock.com

There are concerns that doctors could misdiagnose diabetes in India due to higher rates of type 2 diabetes in younger and slimmer people. A new study has shown that an existing genetic test could accurately diagnose diabetes in people of Indian heritage.

Although people often use the word diabetes to describe one condition, there are actually two different types of diabetes.

Type 1 diabetes is an autoimmune disease that causes damage to the beta cells in the pancreas that produce insulin. A lack of insulin is the primary characteristic of type 1 diabetes.

Treatment involves regular injections with insulin.

Type 2 diabetes is the more common form of diabetes. It is not an autoimmune condition and typically involves resistance to rather than a lack of insulin.

Treatments include medications to increase insulin sensitivity and lifestyle changes, such as following a healthful diet.

Previously, experts have associated the two forms with different age groups:

However, this view is shifting due to rising rates of childhood obesity and recent findings that type 1 diabetes can occur later in life.

This has led to concerns regarding misdiagnosis, particularly in Indian populations, where there is a higher prevalence of type 2 diabetes in younger and slimmer people.

Furthermore, scientists have carried out most research on type 1 diabetes in European populations, which means existing diagnostic tools may not apply.

Misdiagnosis in diabetes is a growing concern. One recent study of 583 participants from the population-based Exeter Diabetes Alliance for Research in England (DARE) in the United Kingdom found that almost 40% of adults with type 1 diabetes did not receive a correct initial diagnosis and received treatment for type 2 diabetes.

Diagnosing diabetes accurately is vital because administering the wrong treatment could have severe consequences, such as diabetic ketoacidosis.

Diagnosing the right diabetes type is an increasingly difficult challenge for clinicians, as we now know that type 1 diabetes can occur at any age. This task is even harder in India, as more cases of type 2 diabetes occur in people with low BMI, explains Dr. Richard Oram of the Institute of Biomedical and Clinical Science at the University of Exeter Medical School in the U.K.

A collaborative study between researchers in Hyderabad in India and the University of Exeter has looked at the effectiveness of current genetic risk scores for diagnosing type 1 diabetes in Indian populations.

The authors published the study in Scientific Reports.

The researchers assessed whether the genetic risk score can effectively discriminate between type 1 and type 2 diabetes in people from Pune in the west of India, who were of Indo-European ancestry.

They analyzed 262 people with confirmed type 1 diabetes, 345 people with type 2 diabetes, and a control group of 324 people who did not have diabetes. They then compared the outcomes with those of European people from the Wellcome Trust Case Control Consortium study.

The researchers found that the current genetic risk score is effective at diagnosing diabetes in Indian populations, even though the original data were from European people.

However, the team also identified new genetic differences between European and Indian populations, making the test more accurate for Indian people.

They found nine new genetic variants (single-nucleotide polymorphisms, or SNPs) that correlate with type 1 diabetes in both groups that doctors could use to predict the onset of the disease in Indian people.

Its interesting to note that different SNPs are more abundant among Indian and European patients. This opens up the possibility that environmental factors might be interacting with these SNPs to cause the disease, explains Dr.G. R Chandak, the scientist leading the study at the CSIR-Centre for Cellular and Molecular Biology in Hyderabad, India.

The results are good news for doctors using this score to diagnose people in India.

We look forward to using this test in diabetic patients from different parts of India, where the physical characteristics of diabetic patients differ from the standard description.

Dr. Chittaranjan Yajnik, KEM Hospital & Research Centre in Pune, India

However, India is a vast country with a lot of genetic diversity, so researchers must also validate this test in other ethnic groups.

Over time, the team hopes to develop a genetic test for type 1 diabetes specific to people with Indian ancestry.

A combined approach, including both genetic risk scores and clinical features, such as auto-antibodies indicative of type 1 diabetes), will be the most effective way to diagnose the disease.

The rest is here:
Genetic diabetes test effective in people of Indian heritage - Medical News Today

FP TrendingJun 26, 2020 13:48:02 IST

Scientists are developing a one-off treatment that appears to permanently cure Parkinson's disease in mice.

The results of the study, conducted by researchers from the University of California, were published in the scientific journal Nature.

According to study authors, they hope that the same approach can be used to treat a wide range of neurodegenerative conditions in human beings.

According to a report in IFL Science, Parkinson's and other types of dementia occur when neurons become damaged and die. Scientists have spent decades trying to come up with treatments to protect the brain cells or generate new ones to replace the ones that are lost.

Study authors have now been able to achieve this by altering a single gene.

The report mentions that researchers tweaked the genetic code of non-neuronal brain cells called astrocytes in petri dish. The astrocytes facilitate communication throughout the brain by producing a protein called PTB which ensures that they do not transform into neurons.

When researchers blocked the production of PTB, the astrocytes transformed into neurons.

Left: mouse astrocytes (green) before reprogramming; Right: neurons (red) induced from mouse astrocytes after reprogramming with PTB antisense oligonucleotide treatment. Image credit: University of California

According to a statement released by the University of California, lead author Xiang-Dong Fu said, "Researchers around the world have tried many ways to generate neurons in the lab, using stem cells and other means, so we can study them better, as well as to use them to replace lost neurons in neurodegenerative diseases," adding, "The fact that we could produce so many neurons in such a relatively easy way came as a big surprise.

As per a report in Eurekalert, researchers developed a noninfectious virus that carries an antisense oligonucleotide sequence and administered it directly to the mouse's midbrain, which is responsible for regulating motor control and reward behaviours and the part of the brain that loses dopamine-producing neurons in Parkinson's disease. A control group of mice received a mock treatment.

According to the report, in the mice that were properly treated, a small subset of astrocytes converted to neurons, increasing the number of neurons by approximately 30 percent. Researchers also found that Dopamine levels were restored to a level comparable to that in normal mice. They found that the neurons grew and sent their processes into other parts of the brain and the mice returned to normal within three months after a single treatment.

Find latest and upcoming tech gadgets online on Tech2 Gadgets. Get technology news, gadgets reviews & ratings. Popular gadgets including laptop, tablet and mobile specifications, features, prices, comparison.

Originally posted here:
Scientists reverse Parkinsons disease in mice by tweaking the genetic code of non-neuronal brain cells - Firstpost

A research program pioneering the use of whole genome sequencing has diagnosed hundreds of patients with rare diseases and discovered new genetic causes of disease.

The international study, published today in Nature, included a researcher and haematologist from The University of Western Australia and PathWest.

The study focused on patients with rare disease in the UK National Health Service. Professor Wendy Erber, from UWAs Faculty of Health and Medical Sciences and a PathWest haematologist, provided key input through her analysis of the blood cells and blood count results.

Professor Erbers analysis, combined with sophisticated new bioinformatic computing tools and software developed specifically for the project, has provided ground-breaking insight into the genetic basis of rare diseases.

This integrated approach was critical to the analysis and understanding of such large, complex and unique sets of biological data for patients with these rare conditions, Professor Erber said.

The researchers, led by the UK National Institute for Health Research BioResource and Genomics England, studied the entire genomes, or 3.2 billion DNA letters, of almost 10,000 patients with rare diseases that affect the blood, the immune system and other tissues.

They identified genetic changes causing some known rare diseases, and, described some completely new genetic diseases. Although individual rare diseases affect a very small proportion of the population, there are thousands of rare diseases and, together, they affect more than one million people in Australia.

The sophisticated analysis identified 95 genes very likely to cause rare diseases, including unexplained bleeding disorders and immune deficiency syndromes that lead to the inability of the body to fight infections.

Study participants now know the cause of their clinical problems and finally have a confirmed diagnosis, Professor Erber said.

Patients with these rare diseases can now receive the most appropriate treatment for their condition. This is already leading to improved patient care.

The genetic results from the research are now being translated into clinical practice and will be rolled out as a standard of care throughout the UKs National Health Service.

This type of research is incredibly important to combat rare genetic diseases. I hope the findings will have an influence on the standard of care in Australia, Professor Erber said.

The benefits will include quicker diagnosis for patients, improved understanding of the reasons they suffer from disease, improved provision of treatment and reduced costs for health services.

Professor Wendy Erber (UWA School of Biomedical Sciences) 08 6457 2325 / 0418 610 600Nicholas Smith (UWA Media Officer)08 6488 1888 / 0411 644 492

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Ground-breaking research uncovers genetic causes of rare diseases - University News: The University of Western Australia

REDONDO BEACH (CBSLA) Rhys Devine was born in the pandemic a quarantine baby full of love and the apple of her parents eyes.

She is happy, Ceri Devine, Rhys mother, said. She is smiley.

But a few months after she was born, her parents noticed something seemed off.

Everyone kept telling me, Its nothing. Shes just behind on her development, and I kind of just, Ceri said. I felt like there was something wrong.

Rhys was struggling to hold herself upright, so her parents took her to the doctor.

The pediatrician had us come in right away, and she examined her and that was when she expressed her concern that it might be spinal muscular atrophy, Ceri said. I remember googling it on my way home from the pediatrician and the first thing that came up was, you know, most infants diagnosed with SMA do not live past two years of age, and I just started crying.

Spinal Muscular Atrophy Type 1 is a devastating genetic disease in infants that causes their muscles to waste away, eventually making it difficult to do things like move, eat and even breathe.

These infants would then become progressively weaker and weaker and weaker until they cant breathe, Dr. Perry Shieh, UCLA professor of neurology, said. The parents who choose to keep them alive they would actually have to get a ventilator.

The Devines doctors told them about two brand new, potentially lifesaving drugs, but there was a catch.

He gave us some hope telling us that the Spinraza and the Zolgensma were options to help have Rhys potentially live into retirement age, Rory Devine, Rhys father, said. But then he also told us that the cost of one dose of Zolgensma is $2.1 million dollars.

The family is determined to give Rhys a fighting chance. To help, friends started a GoFundMe page to help cover the enormous costs of care.

Doctors said now its a race against time.

This is like a down hill, and you cant actually climb back up the hill, Shieh said. So what we like want to do is emphasize that its important to be able to identify our patients as early as possible.

On Wednesday, California started screening all newborn babies for SMA before they leave the hospital, a move doctors said would be a game changer in guaranteeing treatment.

As for the Devine family, they have a long road of treatments ahead and have created a website where they will be documenting their journey.

Link:
I Just Started Crying: Redondo Beach Baby Diagnosed With Rare Genetic Disease That Will Cost Millions To Treat - CBS Los Angeles

Adults under 40 who develop cancers that are rare for their age bracket have a high rate of inherited gene mutations associated with cancer.

People with inherited genetic mutations who develop such cancersknown as early-onset cancersare more likely to develop new malignancies unrelated to their first cancer and to experience other health complications.

The most common early-onset cancers, which by definition are rare malignancies among younger adults, are breast, colon, pancreas kidney, prostate and ovarian cancer. These are distinct from other types of cancer that are more commonly seen among young adults, such as sarcoma and brain cancer.

Thus, the new findings from a recent study, presented this week at the American Association for Cancer Research (AACR) Virtual Annual Meeting II, have important implications for how younger adults with cancer might receive genetic counseling that could inform their treatment as well as their ongoing monitoring as they progress through life.

This study supports a role for genetic testing irrespective of tumor types, Zsofia Stadler, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, said at an AACR press briefing.

Stadler and her colleagues assessed inherited genetic mutations among 1,201 young adults diagnosed with cancer at Sloan Kettering between 2015 and 2019, looking specifically for up to 88 genes known to be linked to a higher risk of cancer.

Eight hundred seventy-seven of the participants had early-onset cancermost commonly colorectal, breast, kidney, pancreatic and ovarian cancer; 324 had young-adult cancers that are common in this age groupmost commonly sarcoma and brain, testicular and thyroid cancer.

The researchers found that 21% of those with early-onset cancers and 13% of those with young-adult cancers had inherited genetic mutations (also known as germline mutations).

Among people with early-onset cancers, BRCA gene mutations and those associated with Lynch syndrome (the most common cause of hereditary colon cancer) were seen most often. Among those with young-adult cancers, inherited TP53 mutations were more common; these are characteristic of Li-Fraumeni syndrome, which is associated with childhood cancers.

Although they only represent about 4% of all cancers, young adults with cancer, defined as those diagnosed with cancer between the ages of 18 and 39, face unique challenges, said Stadler. Identifying whether a young patients cancer occurred in the setting of an inherited cancer predisposition syndrome is important as it can result in a substantial change in clinical management, such as increased cancer surveillance aimed at early detection and risk-reducing surgery to prevent new cancers and may even have reproductive implications for young families.

To read the study abstract, click here.

To read a press release about the study, click here.

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Inherited Genetic Mutations Are Common in Young Adults With Early-Onset Cancer - Cancer Health Treatment News

Over the past few weeks, 23andMe and other genetic testing companies have made headlines for releasing candid statements acknowledging that their field and their products are too white. Its a problem with which geneticist Tshaka Cunningham is all too familiar.

As executive director of the nonprofit Faith Based Genetic Research Institute, Cunningham has traveled widely to speak at Black churches about the value of genetic research. And as co-founder and chief scientific officer of a genetics startup called TruGenomix, hes working to recruit more diverse cohorts to build a genetic test for gauging risk of developing PTSD.

Cunningham recently called in to STATs podcast, The Readout LOUD, to discuss genetics and racial inequity and what needs to be done to make the field actually reflect the worlds diversity.

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The transcript of the conversation has been lightly edited for clarity.

So, Tshaka, what do you make of the reckoning that weve seen in the past couple weeks from 23andMe and other genetics companies on these issues?

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You know, I think its actually a really good thing. I was glad to see it from the highest levels from these companies acknowledging an issue that many of us in the research community have known about for quite a long time, which is this lack of representation of diverse genomes in all of our studies and products. Im glad its starting to get deeper attention because I think it is a key issue thats going to impact the effectiveness of all of these tools over time.

Im looking forward to seeing some positive things that they will do to address it. So, you know, the first step is admitting you have a problem and then you go through the steps to rehabilitate. Im hoping that some positive things will come out of this.

What kinds of questions about genetics do you hear from the communities you speak with?

All kinds of questions. And first of all, I say, you know, the work that were doing with the Faith Based Genetic Research Institute is very unique in that we are bringing together individuals from the faith communities with scientists who are also people of color, and one of our guiding principles in the work that we do in the community is called the honest broker philosophy. That is, those of us who are imparting the information to the community are also from the community. And what we found is that it really helps us establish a better bond of trust for folks to be able to receive the information.

Some of the questions that we get when we talk about the value and the benefits of genetic research is the first questions are, you know, are they going to use it to hurt me? Thats the first question we get a lot from African American participants. And, you know, what will they do with the information? Theres a fair bit of distrust out there. And some of it is quite warranted from past transgressions of the medical establishment on the African American community. But once you sort of talk through those issues with folks and really kind of allow them to see some of the potential benefits, then you start getting a high level of interest.

So lets say 23andMe, for example, or one of the large companies, were to call you and ask for advice on what to do to make their products less Eurocentric and more inclusive. What would you tell them?

Start by making sure that your team, your executive team specifically, is representative of the community. A lot of companies sort of say, well, we cant find them. Any company needing to find a talented minority geneticist give me a call. Ive got a long list.

The second step would be to really use some of your resources to sponsor more research in this area. I mean, part of the challenge is also a financial and economic challenge. When you think about the economic disparities that have existed in America based on racial lines you know, the average African American has seven times less wealth than the average Caucasian. So they might not have even a hundred bucks to spend on something like genetic testing that could benefit them.

And then theres also the messaging. I think to the extent that these companies could help organizations like ours, the Faith Based Genetic Research Institute, other academic institutions, with messaging about the importance or the potential benefits of this, that would be great.

Now, I know thats a fine line that they have to walk because, you know, you dont want to seem coercive. But at the same time, I think trying to really do authentic outreach to the community would start with having more of your employees be from the community and then having a dedicated effort of that kind of outreach within your operation.

One of the more controversial questions in this conversation is around compensation. So what do you think? Do you think that 23andMe should pay people in the Black community and other underrepresented populations for their data?

I believe anybody that contributes their data should have the opportunity to get paid for it if its used. I do not believe in coercing someone to contribute their data with payment. But if Im an individual who has contributed and then you go and use my my data lets say a pharma company buys access to my data and I dont see any benefit from it, then that feels a bit un-American and I just dont feel like its fair. But thats my personal opinion.

So lets talk a little bit about polygenic risk score tests, which really encapsulate the diversity problems in genetics. So, for readers who are unfamiliar with them, these are tests that gather multiple genetic variants together and use them to predict someones chances of developing a disease. So far, many commercial polygenic risk score tests have come off warnings that theyre not very accurate or are even useless in people who are not of European ancestry. But your startup, TruGenomix, is working on a polygenic risk score test to try to gauge risk for developing PTSD. And youre trying to build the test using more diverse data. Tell us about your approach.

Ive recognized the importance of diversity in your datasets. From my earliest days, when I was at the Department of Veterans Affairs, we had a large genomics project called the Million Veteran Program. And part of my contribution to that project was to make sure that minority veterans participated. And so we actually went to great effort to ensure that. And that project has done very well to the credit of the VA, to recruit minority veterans. So that data set is going to provide some rich understanding, or has that potential to provide rich understanding, in polygenic risk for minority communities.

I took some of what I learned there from having to really take the time to do the outreach to the communities, to make sure that the end products are representative. I think that is just core to our actual DNA as a company. I think part of that has to do with the fact that were one of the very few minority-owned genomics companies in the country right now. This was top of mind for us. We wanted to make sure that whatever products we were putting out, the polygenic risk related to all communities, specifically the African American community, which my founders and I come from. It was just a very important thing for us to do not only for societal and ethical reasons, but also for scientific integrity reasons, because as a scientist, I dont believe in putting out products that arent probably applicable to all communities.

So why havent other makers of polygenic risk score tests taken this more holistic approach?

You know, I cant speak for them. I mean, I dont know. Thats a question that I have. I would hope that they take a deeper look at it. Maybe their market calculations were, OK, the people using genetic tests now tend not to be people of color. And therefore, we dont need to care about them. I dont know. Youll have to ask them that question.

All I could say is that I hope that all of the companies that are making these kinds of tests really take diversity seriously. Ive given lectures around diversity and genetics in the past. The majority of the DNA in the world is not of Caucasian origin. Its actually of Asian origin. And then African and Latino. And then Caucasians are only maybe about 14% of all the DNA out there just based on population. So when you think about it in that respect, if you really want to have a genome that is globally applicable, then youd really need to focus on its diversity.

Tshaka, thank you for coming on the podcast today.

Great. Its great being with you all today.

Theresa Gaffney contributed to this report.

This is a lightly edited transcript from arecent episodeof STATs biotech podcast, The Readout LOUD. Like it?Consider subscribing to hear every episode.

Read more here:
A geneticist advocates for diversity and fixing his industry in the process - STAT

The impetus for the campaign can be traced back to a crime spree in the northern Chinese region of Inner Mongolia. For nearly three decades, the police there investigated the rapes and murders of 11 women and girls, one as young as 8. They collected 230,000 fingerprints and sifted through more than 100,000 DNA samples. They offered a $28,000 reward.

Then, in 2016, they arrested a man on unrelated bribery charges, according to the state news media. Analyzing his genes, they found he was related to a person who had left his DNA at the site of the 2005 killing of one of the women. That person, Gao Chengyong, confessed to the crimes and was later executed.

Mr. Gaos capture spurred the state media to call for the creation of a national database of male DNA. The police in Henan Province showed it was possible, after amassing samples from 5.3 million men, or roughly 10 percent of the provinces male population, between 2014 and 2016. In November 2017, the Ministry of Public Security, which controls the police, unveiled plans for a national database.

China already holds the worlds largest trove of genetic material, totaling 80 million profiles, according to state media. But earlier DNA gathering efforts were often more focused. Officials targeted criminal suspects or groups they considered potentially destabilizing, like migrant workers in certain neighborhoods. The police have also gathered DNA from ethnic minority groups like the Uighurs as a way to tighten the Communist Partys control over them.

The effort to compile a national male database broadens those efforts, said Emile Dirks, an author of the report from the Australian institute and a Ph.D. candidate in the department of political science at the University of Toronto. We are seeing the expansion of those models to the rest of China in an aggressive way that I dont think weve seen before, Mr. Dirks said.

In the report released by the Australian institute, it estimated that the authorities aimed to collect DNA samples from 35 million to 70 million men and boys, or roughly 5 percent to 10 percent of Chinas male population. They do not need to sample every male, because one persons DNA sample can unlock the genetic identity of male relatives.

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China Is Collecting DNA From Tens of Millions of Men and Boys, Using U.S. Equipment - The New York Times

Keith McArthur is the CEO of CureGRIN Foundation and creator and host of Unlocking Brysons Brain.

Around Fathers Day in 2018, scientists told me the unthinkable that it might be possible to cure my son Brysons rare genetic disease.

Bryson has GRIN Disorder, caused by a mutation in his GRIN1 gene that prevents him from walking or talking or feeding himself. Even though hes 13, his brain functions at the cognitive level of a toddler, according to a recent report from a developmental psychologist.

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So when researchers told us his symptoms might some day be reversed, I dedicated my life to connecting scientists and pushing for a cure.

But the more I learn, the more I struggle with an important ethical question: Is it ableist to want to cure my son?

Cure is a loaded term. For parents of kids with rare diseases, its a no-brainer. Of course, we should want to give our kids the life they were supposed to have. Of course, we should want to help them.

But for many people living with disabilities, cure implies theres something wrong with them, something that needs fixing. And some people who rely on wheelchairs say that even if there were a cure that could allow them to walk, they wouldnt want it.

As Brysons dad, Ive always thought of myself as an advocate for disability rights. I proudly stood up to the local school board to argue people with special needs deserve more of a say about where they go to high school. Ive leveraged my privilege to complain about broken elevators and insufficient handicapped parking.

And it felt like my efforts to bring together researchers and push for a cure was the ultimate act of advocacy for my son and others like him.

But the other day, someone I dont know called me ableist.

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The accusation came in a negative review for Unlocking Brysons Brain, a podcast series about my son. The reviewer identified as someone with a lifelong physical disability and said my familys obsession with getting a cure made them feel uneasy and uncomfortable.

Im sorry, but this guys is not a disability advocate. Hes an ableist who is obsessed with transformation, the reviewer wrote.

The podcast has elicited positive feedback from many other people with disabilities; so Im wary of overreacting to one negative review. But as much as I want to push back and say, Thats not who I am, theres part of me that wonders whether theres truth in that review.

Am I obsessed with cure? Maybe I am. In addition to my search for a cure for Bryson, and my podcast about this search, Im also chief executive of CureGRIN, an organization focused on finding a cure for GRIN Disorder.

Even my Twitter bio identifies me as a rare disease dad searching for a cure. So yes, Ive internalized this search for a cure and made it part of my personal identity.

But does that mean its wrong?

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It doesnt feel wrong. After all, I worry that Bryson cant communicate his wants and desires, that he cant pilot his own wheelchair, that he cant defend himself from those who might want to do him harm. Im worried about his violent episodes when he flails around until hes covered in bruises and bites himself so hard were worried hell tear an artery. Im terrified about whats going to happen to Bryson when his mother and I arent around to look after him. Dont I owe it to Bryson to push for medicines that can give him more agency and security?

But how much cure is too much? Is it moral to push for safety and autonomy, but ableist to wish for a cure that could make Bryson neurotypical?

Because if Im being honest, thats what I want. If there were a magic pill that could make Bryson fully neurotypical, I would give it to him. I want him to be able to walk on his own, and feed himself, and tell me what his life has been like for the past 13 years. And when hes grown up, I want him to be able to live independently, and have a job, and get married and have kids.

Bryson is perfect; hes extraordinary. But I want more than that. I want him to be able to choose to be ordinary.

The trouble is that Bryson cant choose. Yes, hell sometimes make simple choices, for example by reaching to indicate if he wants pudding or applesauce as a snack.

But when I ask him whether he wants me to continue on with this journey to find him a cure, he just looks back at me with his big beautiful eyes.

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So even though I understand that cure is an ethical quagmire, I feel compelled to carry on.

The question is how to push for a cure for Bryson without making others living with disabilities feel uneasy and uncomfortable.

As part of my journey, Ive spoken with ethicists and activists with disabilities about the concept of cure and how to make sure I pursue my quest in an ethical way.

Part of the solution is to make sure Im giving Bryson as much of a voice as possible. Even if he cant answer complex questions around a cure yet, its important that Im always asking myself: What would Bryson want? And is it different from what I want for him? And if there are partial therapies in the future that could allow Bryson to communicate, I need to be willing to listen to what he has to say about this journey for a cure.

Its also critical that I recognize that a cure for Bryson may never come. And even if there are therapies that can make a radical difference in his life, therapies that can provide safety and agency, they are not likely to make Bryson neurotypical. Bryson is likely to live out the rest of his life as someone with high needs.

And thats okay. Because Bryson is already perfect. Its the world that isnt.

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So if the anonymous reviewer is right, if I really am obsessed with transformation, then I need to redirect some of that obsession away from changing my son and toward changing the world. Because thats another way I can help him to be safer and have more autonomy by working to dismantle the barriers, both physical and systemic, faced by all people living with disabilities.

Finally, its critical that I continue to cherish Bryson for who he is today, a vibrant teenager who knows joy and sadness, an extrovert who loves being around people, a loving soul who wraps his arms around his dad and pulls me close, showering me with wet toothy kisses. How many fathers of able-bodied kids will get such a wonderful gift from their teenage sons this Fathers Day?

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I want to cure my son of his rare genetic disease. Is that wrong? - The Globe and Mail

Can a vaccine be an October surprise? Are journal publishers running a racket? And why is genetics so white?

We discuss all that and more this week on The Readout LOUD, STATs biotech podcast. First, we run through a busy week in news, discussing the results of a major study on Covid-19 treatment, an escalating fight in the publishing world, and the drug industrys biggest-ever IPO. Then, physician and health care policy expert Ezekiel Emanuel joins us to discuss his nightmare scenario: President Trump, desperate for re-election, forces the approval of an ineffective coronavirus vaccine. Finally, we talk to geneticist Tshaka Cunningham about the deep racial inequities in the field of genomics and what can be done to correct them.

For more on what we cover, heres the news on a potential Covid-19 treatment; heres more on the the fight over academic publishing; heres a look at inequality in genetics; and heres the latest in STATs coronavirus coverage.

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Well be back next Thursday evening and every Thursday evening so be sure to sign up onApple Podcasts,Stitcher,Google Play, or wherever you get your podcasts.

And if you have any feedback for us topics to cover, guests to invite, vocal tics to cease you can emailreadoutloud@statnews.com.

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Interested in sponsoring a future episode of The Readout LOUD? Email us atmarketing@statnews.com.

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Listen: The latest on Covid-19, vaccine politics, and diversifying genetics - STAT

By Natasa Milas

Preserving the tiger population in the Indian subcontinent is a passion with Uma Ramakrishnan, an assistant professor at the National Centre for Biological Sciences (NCBS), Bengaluru, and one of Indias leading scientists. Her work focuses on population genetics and the evolutionary history of mammals.Data from Ramakrishnans work has been used for creating and improving plans for conservation of tigers in a rapidly urbanising India. In 2013, Ramakrishnan and her teams data was used as evidence in the Supreme Court to petition for an underpass for the widened National Highway 7 to enable tiger connectivity between Kanha and Pench tiger reserves in Madhya Pradesh.Ramakrishnan was a 2015-16 Fulbright-Nehru Academic and Professional Excellence Fellow at Stanford University, California. She is the first Indian to win the Parker/Gentry Award, administered by The Field Museum in Chicago in recognition of her work on conservation efforts. Excerpts from an interview:

How did you become interested in population genetics?I was always interested in the natural world and in understanding animal behaviour. I was lucky to grow up on the Indian Institute of Science campus in Bengaluru. My curiosity as a child always extended beyond simply observing the natural world. I asked myself: Why do animals behave the way they do? What is actually transpiring in these animal populations? Early on, I realised that there was a hidden layer of information that we were not considering DNA and genetic variation.After high school, I accompanied my family to Princeton University, USA, where my father was on a sabbatical. There I spent time in a molecular ecology lab and could gain deep insights into biology by understanding this hidden information layer. I knew then that I wanted to use a genetics lens to study wildlife populations.After my studies, I was lucky to get a job at the National Centre for Biological Sciences, part of the Tata Institute of Fundamental Research, Bengaluru. I was their first hire in the ecology and evolution area. Soon after, I got a call from conservation zoologist and tiger expert Ullas Karanth, asking if I was interested in working on tigers and their genetics. My journey over the last 15 years or so at NCBS, understanding tigers and other Indian biodiversity, has been incredibly exciting.

How is your work helping to preserve the tiger population in India?The future of tigers is really in our hands. Thanks to the efforts of the Government of India, several tiger populations have recovered. The viability and future survival of these populations will be contingent on our ability to maintain connectivity between them.I hope our research has and will continue to fill the gap between science, management and policy. We are currently working on an isolated population of tigers in Rajasthan and I hope our research insights will help plan what may be the best way to ensure long-term survival of this population.

How has your experience at the Stanford University as a Fulbright Fellow helped your current work in India?This was a really great opportunity. After nine years at NCBS a sabbatical sounded great. I was outside my comfort zone at Stanford University, the academic mecca for population genetics. Additionally, Stanford is nestled in the San Francisco Bay Area, where many conservation NGOs and start-up companies at the forefront of new genomic technologies are based.The amazing thing about being outside your comfort zone is that its empowering. With colleagues at Stanford, we turned what has typically been a challenge for conservation genetics non-invasive or poor-quality DNA samples into a strength. We asked whether we could develop cheap, reliable and fast methods that used novel genomic technologies to work on poor-quality samples. While there, my colleagues and I set up the Program for Conservation Genomics. Our goal was to provide simple-to-use genetic approaches to on-ground conservationists. We are still working together to make this a reality.

What are some of the biggest challenges in your work?Permissions to work in protected areas are always very challenging. Then, there are the things you really have no influence over. It rains and, well, your samples collected over the next few days are unlikely to have DNA or yield results. Sometimes, we work with large teams or in areas which are very difficult (for example, high elevation), inaccessible or not very politically stable.

What are your future research plans?I would really like to build partnerships with other tiger researchers across Asia. The methods we developed while at Stanford are going to be generalizable across tiger range countries. One of the goals is that everyone across the world can use a common platform for analyses, so that the data is comparable. Critical to this effort, however, is that each country builds an ecosystem to generate and analyze their genetic data on tigers locally.We are working hard to understand the impacts of inbreeding or mating between relatives on small and isolated tiger populations. This is a big ask for a species like tiger, but I am hoping the detailed work we are doing could shed some light on this problem, which is sure to become more common with time.I hope that our research can contribute in whatever small way to reverse biodiversity loss. (SPAN-TWF)

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Genetics study helps tiger conservation The Shillong Times - The Shillong Times

Abstract

Developmental shifts in stage-specific gene expression can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events. We found that the high-altitude Tibetan antelope (Panthelops hodgsonii) has evolved an adaptive increase in blood-O2 affinity by truncating the ancestral ontogeny of globin gene expression such that a high-affinity juvenile hemoglobin isoform (isoHb) completely supplants the lower-affinity isoHb that is expressed in the adult red blood cells of other bovids. This juvenilization of blood properties represents a canalization of an acclimatization response to hypoxia that has been well documented in adult goats and sheep. We also found the genomic mechanism underlying this regulatory isoHb switch, revealing how a reversible acclimatization response became genetically assimilated as an irreversible adaptation to chronic hypoxia.

When members of multigene families are developmentally regulated, shifts in the stage-specific expression of individual genes can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events (heterochrony). For example, retained activity of early-expressed genes in later stages of ontogeny can result in the retention of juvenile characters into adulthood, a well-documented developmental mechanism of phenotypic evolution (1, 2). In extreme cases, deceleration of development can produce a truncation of the ancestral ontogeny, resulting in the juvenilization of the adult-expressed phenotype, a phenomenon known as pedomorphosis.

In jawed vertebrates, the subfamilies of genes that encode the - and -type subunits of tetrameric hemoglobin (Hb) are developmentally regulated such that structurally and functionally distinct 22 Hb isoforms (isoHbs) are expressed during different ontogenetic stages. During mammalian development, different pre- and postnatally expressed isoHbs have evolved different oxygenation properties and perform distinct O2-scavenging/O2-transport tasks during different ontogenetic stages (36). Genetically based shifts in stage-specific isoHb expression could therefore provide a heterochronic mechanism of evolutionary change in respiratory gas transport and aerobic metabolism. Similarly, in humans, hereditary persistence of fetal Hb alleviates the severity of thalassemias and other pathologies affecting the synthesis or stability of adult Hb (7).

Prenatally expressed isoHbs of eutherian mammals typically exhibit substantially higher O2 affinities than adult-expressed isoHbs (3, 5, 6). In anthropoid primates and bovid artiodactyls, expression of a high-affinity fetal isoHb during late stages of prenatal development helps to maintain an O2 affinity difference between fetal and maternal circulations, thereby facilitating O2 transfer across the placental barrier (5, 6). Given that increased Hb-O2 affinity is generally beneficial under conditions of severe hypoxia due to the importance of safeguarding arterial O2 saturation (6, 811), the retention of early isoHb expression into adulthood could provide an effective mechanism of adaptation to chronic O2 deprivation. Consistent with this hypothesis, when adult goats and sheep are exposed to acute hypoxia, they up-regulate a juvenile isoHb at the expense of the normal adult isoHb (12, 13). Here, we report the discovery of a canalized version of this response in the high-altitude Tibetan antelope, Panthelops hodgsonii (Artiodactyla: Bovidae), a champion among mammals in aerobic exercise performance under hypoxia. This species is endemic to the Tibetan Plateau and lives at altitudes of 3600 to 5500 m above sea level. At an altitude of 5500 m, the partial pressure of O2 (PO2) is roughly half the value at sea level, a level of hypoxia that severely compromises aerobic exercise performance in humans and most other mammals (1416). However, at these altitudes, Tibetan antelope can sustain running speeds of >70 km/hour over distances of >100 km (17).

In addition to documenting the phenotypic consequences of developmentally displacing the low-affinity adult isoHb with a higher-affinity juvenile isoHba form of biochemical pedomorphosiswe also found the genomic mechanism by which the up-regulation of the juvenile isoHb became canalized in Tibetan antelope. Specifically, we document how a reversible acclimatization response to acute hypoxiaas observed in modern-day sheep and goatsbecame genetically assimilated as an irreversible adaptation to chronic hypoxia.

We characterized the genomic organization of globin genes in Tibetan antelope and other bovid artiodactyls using published genome assemblies (18). Among mammals, bovid artiodactyls are unusual in that the entire -globin gene cluster has undergone multiple rounds of en bloc duplication involving the same set of pre- and postnatally expressed -type globin genes (Fig. 1) (1921). Cows (Bos taurus) have two duplicated gene blocks, each containing separate paralogs of the -globin gene, A and F, in the 5 and 3 blocks, respectively (Fig. 1). As with other eutherian mammals, the product of A is incorporated into an adult-expressed isoHb, HbA (2A2), whereas the F gene has been recruited for prenatal expression and is incorporated into a fetal isoHb, HbF (2F2) (22). Goats (Capra hircus) and sheep (Ovis aries) have an additional gene block at the 5 end of the cluster that contains a third -globin paralog, C (Fig. 1) (1921). Whereas the A and F genes in goats and sheep have retained the same developmental expression profiles as their respective orthologs in cow, the C gene has been recruited for a new ontogenetic stage of expression during the first few months of neonatal life, and its product is incorporated into a juvenile isoHb, HbC (2C2) (23).

Colored boxes represent individual genes. Labels denote previously annotated C-, A-, and F-globin genes.

The -globin gene cluster of Tibetan antelope appears superficially similar to that of cow in terms of gene content (Fig. 1), suggesting that the Tibetan antelope inherited the same pair of A- and F-containing gene blocks. The alternative hypothesis is that Tibetan antelope inherited the additional en bloc duplication observed in goats and sheep but one of the triplicated gene blocks was secondarily deleted, in which case the sole remaining pair of -globin genes would be represented by one of three possible combinations: A + F (a reversion to the ancestral gene complement observed in cow), C + A, or C + F (Fig. 2, A to C). Either of the latter two combinations would implicate a novel isoHb profile that is not observed in other bovid taxa. To distinguish among these three alternative scenarios, we estimated the phylogeny of bovid C, A, and F genes and the pair of Tibetan antelope -globin paralogs. Estimated phylogenies (Fig. 2D and fig. S1) demonstrate that the 5 and 3 -globin genes of Tibetan antelope are orthologous to bovid C and F, respectively, consistent with the scenario illustrated in Fig. 2B. This result indicates that Tibetan antelope inherited the triplicated set of C-, A-, and F-containing gene blocks observed in goats and sheep (Fig. 1) and that the middle gene block containing A was secondarily deleted. This phylogenetic inference is unambiguously corroborated by patterns of conserved synteny and pairwise sequence matches (Fig. 3), as the C- and F-containing gene blocks of goat and sheep match the 5 and 3 gene blocks in Tibetan antelope. This comparative genomic analysis revealed that a ~45-kb region of the Tibetan antelope -globin gene cluster was deleteda gene region that contained the ortholog of the A gene that encodes the chain of adult Hb in bovids and all other mammals.

Alternative histories of gene deletion in Tibetan antelope yield testable phylogenetic hypotheses: (A) Deletion of C, (B) deletion of A, and (C) deletion of F. (D) Estimated maximum likelihood phylogeny of bovid -type globin genes indicates that Tibetan antelope has retained copies of C and F and that A has been secondarily lost. Bootstrap support values are shown for relevant nodes.

Purple, green, and blue colored boxes represent genes within the C-, A-, and F-gene blocks, respectively. (A) Gray shading denotes percent sequence identity between homologous -globin gene clusters. (B) A ~45-kb chromosomal deletion in the -globin cluster of the Tibetan antelope lineage resulted in secondary loss of the A-containing gene block.

Deletion of the adult A gene in the ancestor of Tibetan antelope effectively truncated the ancestral ontogeny of globin gene expression, such that juvenile HbC completely supplanted HbA in adult red blood cells. Thus, blood-O2 transport in Tibetan antelope has been juvenilized relative to the ancestral phenotype of adult bovids. To examine the effects of this pedomorphic change, we measured the oxygenation properties of purified recombinant Hb from Tibetan antelope and purified native Hbs from adult specimens of 10 other bovid species (Fig. 4 and Table 1). The adult red cells of these other taxa contain HbA alone or in combination with HbC as a minor component (fig. S2). We measured the Hb-O2 affinity of purified total Hb from each bovid species in both the absence (stripped) and presence of 100 mM Cl (in the form of KCl). The stripped treatment provides a measure of intrinsic Hb-O2 affinity, whereas the +KCl treatment provides a measure that is relevant to in vivo conditions in bovid red cells, as Cl ions are the principal allosteric regulators of Hb-O2 affinity (i.e., heme reactivity is modulated oxygenation-linked binding of Cl ions at sites remote from the heme iron) (6, 22, 24). Results of our in vitro experiments revealed that Hb of Tibetan antelope has a substantially higher O2 affinity than that of all other bovid taxa (Fig. 4 and Table 1). Hbs of all taxa were similarly responsive to Cl, as the average P50 (the PO2 yielding 50% Hb-O2 saturation) was 27.1% higher (i.e., Hb-O2 affinity was lower) in the +KCl treatment (Table 1).

O2 tensions at half saturation (P50) for total Hb in the absence (stripped; gray hatched bars) and presence of 0.1 M KCl (black bars) at 37C (pH 7.4) (0.1 mM Hb4). Values are shown as mean P50 SEM (n = 3).

P50 values are reported as means SEM. Cl effect calculated as logP50[+KCl] logP50[stripped].

As a follow-up experiment, we isolated and purified HbC and HbA from two of the bovid species expressing both components, and we measured isoHb-specific O2-binding properties to determine how blood-O2 affinity would be affected by elimination of the major HbA isoHb (as would occur with the deletion of the A gene, leaving juvenile HbC as the sole-remaining isoHb). There was very little among-species variation in the measured O2 affinities of either juvenile HbC or adult HbA (Table 1 and fig. S2), but the O2 affinity of HbC exceeded that of HbA by a consistent margin (average, 10.6 torr) in all species (Table 1 and fig. S2). Moreover, O2 affinity of HbC alone was always substantially higher than that of the composite HbA + HbC mixture (with the two isoHbs present in their naturally occurring relative abundance) (Table 1 and fig. S2), reflecting the fact that the lower affinity HbA is always present as the major isoHb in adult red cells (average HbA/HbC ratio = ~80:20).

The higher Hb-O2 affinity of Tibetan antelope relative to that of other bovid species is entirely attributable to a difference in isoHb composition: They only express the high-affinity HbC instead of jointly expressing HbA and HbC (with the lower-affinity HbA present as the major isoHb). To infer the direction of evolutionary change in isoHb-specific O2 affinities and to reconstruct the phenotypic effect of deleting A-globin (thereby leaving HbC as the sole-expressed isoHb in adult red cells), we reconstructed the ancestral bovid A and C genes as well as their single-copy, preduplication progenitor (AC) (Fig. 5 and fig. S3). Triangulated comparison of O2 affinities of the three recombinantly expressed ancestral isoHbs, AncHb-A, AncHb-C, and AncHb-AC (all of which had identical chains), revealed that the juvenile AncHb-C evolved a slight increase in O2 affinity relative to the estimated ancestral state (represented by AncHb-AC), whereas adult HbA evolved a slight reduction in O2 affinity (Fig. 5). These data indicate that if HbA and HbC were present in a 80:20 ratio in the red cells of the Tibetan antelope ancestor (as in extant bovids), then the deletion of A-globin and the consequent elimination of HbA from the HbA + HbC composite mixture would result in a 13.5% increase in Hb-O2 affinity in the presence of 100 mM Cl (P50 decreased from 18.5 to 16.0 torr). Theoretical and experimental results indicate that an increase in Hb-O2 affinity of this magnitudeif accompanied by a corresponding enhancement of tissue O2 diffusion capacitywould likely translate into a physiologically important enhancement of aerobic exercise performance under hypoxia (6, 811).

(A) Reconstructed ancestral -globin genes (C, A, and AC) of bovids. (B) O2 tensions at half saturation (mean P50 SEM, n = 3) for recombinant ancestral isoHbs in the absence (stripped) and presence of 0.1 M KCl at 37C (pH 7.4) (0.1 mM Hb4). Schematic diagrams show the subunit composition of the three ancestral isoHbs (which have identical chains and structurally distinct chains).

The derived blood phenotype of Tibetan antelope is consistent with the theoretical expectation that an increased Hb-O2 affinity is adaptive under conditions of severe hypoxia (especially in highly athletic species) and is consistent with patterns observed in other high-altitude mammals and birds that maintain especially high rates of aerobic metabolism (2533). In other case studies of high-altitude vertebrates, evolved increases in Hb-O2 affinity have been traced to one or more amino acid substitutions in the and/or chain subunits of the 22 Hb tetramer (6, 3132). Here, we document a unique case in which an evolved change in Hb-O2 affinity has been accomplished via a heterochronic shift in globin gene expression, such that a high-affinity, juvenile isoHb supplants the lower-affinity, adult isoHb. This juvenilization of blood properties represents a novel mode of biochemical adaptation and highlights the utility of heterochrony as an adaptive mechanism, whereby the existing channel of ordinary ontogeny already holds the raw material in a particularly effective state for evolutionary change (2).

There has been debate in the literature regarding the relative importance of regulatory versus coding changes in genetic adaptation (34) and phenotypic evolution in general (3536). In the case of Tibetan antelope, the evolved increase in Hb-O2 affinity was caused by an unusual combination of regulatory and structural changes. Specifically, a marked regulatory switch in protein isoform expression (via truncation of the ancestral ontogeny of globin gene regulation) was caused by a large-scale chromosomal deletion, highlighting the unexpected diversity of genetic mechanisms and substrates of phenotypic evolution.

Frozen erythrocytes from 10 bovid species were provided by the San Diego Zoo Institute for Conservation Research (Uniform Biological Material Transfer Agreement BR2017063). This sample included six species in the subfamily Caprinae (Capra aegagrus cretica, Capra caucasica caucasica, Ovis nivicola, Capra nubiana, Ovis orientalis musimon, and Ovis canadensis nelsoni), two species in the subfamily Alcelaphinae (Damaliscus pygargus phillipsi and Connochaetes gnou), and one species of each from Hippotraginae (Addax nasomaculatus) and Bovinae (Bos gaurus).

RNA was extracted from ~100 l of flash-frozen erythrocytes using an RNeasy Universal Plus Mini kit (QIAGEN). Complementary DNA (cDNA) was synthesized from freshly prepared RNA using SuperScript IV reverse transcriptase (Invitrogen). Gene specific primers were used to amplify the - and -type globin transcripts. Polymerase chain reaction (PCR) reactions were conducted using 1 ml of cDNA template in 0.2-ml tubes containing 25 l of reaction mixture [0.5 l of each deoxynucleotide triphosphate (2.5 mM), 2.5 l of 10 Reaction Buffer (Invitrogen), 0.75 l of 50 mM MgCl2, 1.25 l of each primer (10 pmol/l), 1 l of Taq polymerase (Invitrogen), and 16.75 l of double-distilled H2O], using an Eppendorf Mastercycler Gradient thermocycler. Following a 5-min denaturation period at 94C, the desired products were amplified using a cycling profile of 94C for 30 s, 53 to 65C for 30 s, 72C for 45 s for 30 cycles, followed by a final extension period of 5 min at 72C. Amplified products were run on a 1.5% agarose gel, and bands of the correct size were subsequently excised and purified using Zymoclean Gel DNA recovery columns (Zymo Research). Gel-purified PCR products were ligated into pCR4-TOPO vectors using a TOPO TA Cloning kit and were then transformed into One Shot TOP10 Chemically Competent Escherichia coli (Thermo Fisher Scientific). Three to six transformed colonies were cultured in 5 ml of LB medium, and plasmids were subsequently purified with a GeneJET Plasmid Miniprep kit (Thermo Fisher Scientific). Purified plasmids were sequenced by Eurofins Genomics.

Genomic sequences containing the complete - and -globin gene clusters for the domestic goat (C. hircus), sheep (O. aries), cow (B. taurus), and Tibetan antelope (P. hodgsonii) were obtained from GenBank (table S1). Sequence identity between bovid chromosomal regions containing the -globin gene clusters was calculated using Blastn, and patterns of sequence matching were visualized using Easyfig 2.1 (37). Coding sequences of - and -globin genes were extracted from genomic and cDNA sequences available on GenBank (table S1) and were combined with the newly generated cDNA sequences mentioned above (fig. S3). Sequences were aligned using MUSCLE (38) and were then used to estimate phylogenetic trees. The best fitting codon substitution model and initial tree search were estimated using IQ-TREE with the options -st CODON, -m TESTNEW, -allnni, and -bnni (39, 40). Initial trees were then subjected to 1000 ultrafast bootstrap replicates (41). Bootstrap consensus trees (fig. S1, A and B) were used to estimate ancestral globin sequences using IQ-TREE with the option -asr (figs. S1C and S3). As bovid C-globins are truncated by 9 base pairs (relative to A), the ancestral reconstruction of indels in the -globin gene tree was performed by FastML (42).

Blood samples (~200 l) were added to a 5 volume of ice-cold water and incubated on ice for 30 min to lyse the red blood cells. Samples were centrifuged at 20,000g for 10 min to remove cell debris. Buffer was added to the supernatants to a final concentration of 0.01 M Hepes/0.2 M NaCl (pH 7.4) and passed through a PD-10 desalting column (GE Healthcare) equilibrated with 25 ml of 0.01 M Hepes/0.5 mM EDTA (pH 7.2) to remove intracellular cofactors. Desalted lysates were loaded onto a HiTrap SP cation exchange column (GE Healthcare), and isoHbs were eluted using a linear pH gradient [0.01 M Hepes/0.5 mM EDTA (pH 7.2 to 7.7)]. For each species, a subsample of each isoHb was pooled to create a Total Hb solution. Each Hb solution was then desalted using a PD-10 column (GE Healthcare) equilibrated with 0.01 M Hepes/0.5 mM EDTA (pH 7.4), and eluates were concentrated using the Amicon Ultra-4 Centrifugal Filter Units (Millipore).

O2 equilibrium curves for purified Hb solutions [0.1 mM Hb in 0.1 M Hepes/0.05 M EDTA buffer (pH 7.4)] were measured at 37C using the Blood Oxygen Binding System (Loligo Systems). O2 equilibrium curves were measured in the absence (stripped) and presence of chloride ions (0.1 M KCl). Each Hb solution was sequentially equilibrated with three to five different O2 tensions (PO2) at saturation levels between 30 to 70%, while the absorbance was continually monitored at 430 nm (deoxy peak) and 421 nm (oxy/deoxy isosbestic point) (4345). Hill plots (log[fractional saturation/[1 fractional saturation]] versus logPO2) constructed from these measurements were used to estimate the PO2 at half saturation (P50) and the cooperativity coefficient (n50) from the -intercept and slope of these plots, respectively. O2 equilibrium curves for each Hb solution were measured in triplicate, and P50 is reported as means SEM.

Globin sequences for domestic goat, Tibetan antelope, and the reconstructed ancestral globins were synthesized by GeneArt Gene Synthesis (Thermo Fisher Scientific) after optimizing the nucleotide sequences in accordance with E. coli codon preferences. The synthesized globin gene cassette was cloned into a custom pGM vector system along with the methionine aminopeptidase gene, as described previously (46).

Recombinant Hb expression was carried out in the E. coli JM109 (DE3) strain as described previously (4648). Bacterial cell lysates were then loaded onto a HiTrap Q HP anion exchange column (GE Healthcare), then equilibrated with 20 mM tris/0.5 mM EDTA (pH 8.3), and eluted with a linear gradient of 0 to 0.25 M NaCl. Hb-containing fractions were then loaded on to a HiTrap SP HP cation exchange column (GE Healthcare) and eluted with a linear pH gradient (pH 6.8 to 8.4). Eluted Hb factions were concentrated using the Amicon Ultra-4 Centrifugal Filter Units (Millipore), and oxygenation properties were measured as described above.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

S. J. Gould, Ontogeny and Phylogeny (Harvard Univ. Press, 1977).

S. J. Gould, The Structure of Evolutionary Theory (Harvard Univ. Press, 2002).

J. F. Storz, Hemoglobin: Insights into Protein Structure, Function, and Evolution (Oxford Univ. Press, 2019).

M. H. Blunt, T. H. J. Huisman, The haemoglobins of sheep, in The Blood of Sheep: Composition and Function (Springer, 1975), pp. 155160.

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Biochemical pedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope - Science Advances

Researchers say that very few people with autism are undergoing the genetic testing they should. (Dreamstime/TNS)

It is widely recommended that individuals with autism receive a battery of genetic tests, but new research finds strikingly few people on the spectrum partaking.

Just 3 percent of those with autism have received both chromosomal microarray and fragile X testing, according to findings from a study published recently in the journal JAMA Psychiatry.

The American Academy of Pediatrics, the American College of Medical Genetics and the American Academy of Child and Adolescent Psychiatry all recommend both assessments in order to determine more precisely what might underlie an individuals symptoms and point to treatment options, the researchers said.

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The study looked at medical records and self-reported information from 1,280 people with autism ranging in age from 1 to 68 between 2013 and 2019. More than 16 percent of the participants said they had received some variety of genetic testing, with 13 percent having undergone fragile X testing and 4.5 percent receiving chromosomal microarray testing. But, the researchers found that only a small number of people were taking both of the recommended tests.

I had the impression that the frequency of recommended genetic testing was not going to be very high based on the patients I encounter clinically, but 3 percent is actually lower than I thought it would be, said Daniel Moreno De Luca, an assistant professor of psychiatry and human behavior at Brown University who worked on the paper.

The study found that genetic testing is more common for those diagnosed in recent years. Among individuals diagnosed with autism between 2010 and 2014, nearly 10 percent said they had received chromosomal microarray testing, which is a more modern offering. But, adults with autism were unlikely to have had any genetic testing.

Researchers behind the study said their findings highlight a disconnect between research and professional recommendations and whats happening in clinical practice.

This paper is really about how you implement clinical genetic tests in the clinical diagnostic setting, said Eric Morrow, an associate professor of biology at Brown and an author of the study. There is rapid progress from research, and then theres the doctor and health systems that need to translate that to clinical practice.

Original post:
Despite Recommendations, Genetic Testing Rare Among Those With Autism - Disability Scoop

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This report considers the below mentioned key questions:

Q.1. What are some of the most favorable, high-growth prospects for the global Human Genetics market?

Q.2. Which products segments will grow at a faster rate throughout the forecast period and why?

Q.3. Which geography will grow at a faster rate and why?

Q.4. What are the major factors impacting market prospects? What are the driving factors, restraints, and challenges in this Human Genetics market?

Q.5. What are the challenges and competitive threats to the market?

Q.6. What are the evolving trends in this Human Genetics market and reasons behind their emergence?

Q.7. What are some of the changing customer demands in the Human Genetics Industry market?

Table of Contents:

Executive Summary: It includes key trends of the Human Genetics market related to products, applications, and other crucial factors. It also provides analysis of the competitive landscape and CAGR and market size of the Human Genetics market based on production and revenue.

Production and Consumption by Region: It covers all regional markets to which the research study relates. Prices and key players in addition to production and consumption in each regional market are discussed.

Key Players: Here, the report throws light on financial ratios, pricing structure, production cost, gross profit, sales volume, revenue, and gross margin of leading and prominent companies competing in the Human Genetics market.

Market Segments: This part of the report discusses about product type and application segments of the Human Genetics market based on market share, CAGR, market size, and various other factors.

Research Methodology: This section discusses about the research methodology and approach used to prepare the report. It covers data triangulation, market breakdown, market size estimation, and research design and/or programs.

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Here is the original post:
Human Genetics Market Analysis with Key Players, Applications, Trends and Forecasts to 2026 - Farmers Ledger

Express News Service

BENGALURU: A team of researchers from the National Centre for Biological Sciences (NCBS) are using hair shed of tigers to create a genetic database and pedigree of striped cats at Ranthambore Reserve in Rajasthan.

So far, NCBS studied the gene pool using tiger pelts, blood and tissue samples. But now they are using shed hair. In the study titled Are shed hair genomes the most effective non-invasive resource for estimating relationships in the wild? the researchers collected 34 tiger hair samples in Ranthambore during a 256-day study period.

Lead author and research scholar at NCBS Anubhab Khan told TNIE that this was the first-of-its kind of study and the next step of what the team was studying so far. Earlier, tissue and blood samples were used, but getting them was a challenge. We even started direct observation. But since tigers are elusive, we decided to use shed hair for studying genetic database and DNA mapping, he said. Tigers shed hair while scratching, sitting, resting and so on. We found them to be a good sample base for the study. It helped us get precise data because it was also verified with the tissue samples collectedso far.

Spread over an area of 392 sq km, Ranthambore is best known for its tigress Machli (T-16), which died in August 2016. Many, including forest officials, state that most of the tigers in Ranthambore are her lineage and NCBS is studying that.

Khan said two new lineages were reported. In case of T-47, we did not know anything, after the study we found its mother was related to Machli. As for T-24, we have so far found its mothers side has no connection to Machli. Now the fathers side is being studied to draw the family tree, he said. NCBS has around 106 tiger DNA sequences; of these, 100 sequences are from around the world and 60 from India.The researchers are also studying tigers in Similipal National Park, Odisha, and Bandhavgarh National Park, Madhya Pradesh, where many cattle kill cases are reported, with the same method.

What is tiger shed?Like many other mammals, tigers shed their fur or hair once or twice per year. The tiger has a longer winter coat and a shorter summer coat. Hairs are also shed by the bigs cats when they scratch on trees or even while sitting on the ground.

Read the rest here:
Tiger hair to be used to map striped cats genetic roots - The New Indian Express

The "Genetic Testing. Global Market Forecasts for Applications and Technologies. Updated for COVID-19 Pandemic impact with Executive and Consultant Guides 2020 to 2024" report has been added to ResearchAndMarkets.com's offering.

This report explores how the large genetic testing cancer segment has been impacted by COVID-19. Genetic Blizzard is creating a confusing array of new tests. Will all newborns receive Whole Genomic Sequencing at birth? What has happened to Direct to Consumer?

The role of genetics in health and disease is just now being understood. This new knowledge, combined with lower pricing is driving the Genetic Testing industry to record growth. New drugs may only work for people with a certain genetic makeup, and this too is driving the Genetic Testing Industry. The traditional genetic testing market is growing in volume and growing in the breadth of tests creating a new life for the industry. The report forecasts the market size out to 2024. The report includes detailed breakouts for 14 countries and 5 regions.

Predictive Diagnostics? Pharmacogenomic Testing? Direct to Consumer? Find out about the technology in readily understood terms that explain the jargon. What are the issues? Find the opportunities and pitfalls. Understand growth expectations and the ultimate market forecasts for the next five years.

Key Topics Covered:

1. Introduction and Market Definition

1.1 Genetic Testing Definition in This Report

1.2 The Genomics Revolution

1.3 Market Definition

1.4 U.S. Medical Market and laboratory Testing - Perspective

2. Market Overview

2.1 Market Participants Play Different Roles

2.2 Genetic Tests -Types, Examples and Discussion

2.3 Industry Structure

2.4 Market Shares of Key Genetics Players - Analysis

3. Market Trends

3.1 Factors Driving Growth

3.2 Factors Limiting Growth

3.3 Instrumentation and Automation

3.4 Diagnostic Technology Development

4. Genetic Testing Recent Developments

5. Profiles of Key Companies

6. Global Market Size

6.1 Global Market by Country

6.2 Global Market by Application

6.3 Global Market by Technology

7. Market Sizes by Application

7.1 Newborn Testing Market

7.2 NIPT Market

7.3 Predictive Testing Market

7.4 Oncology Testing Market

7.5 DTC Testing Market

7.6 Other Testing Market

8. Global Genetic Testing Market by Technology

9. The Future of Genetic Testing

For more information about this report visit https://www.researchandmarkets.com/r/jp4uin

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Continued here:
Global Genetic Testing Market Forecasts for Applications and Technologies 2020-2024, Updated in Light of Impact of COVID-19 Pandemic -...

A mouse model and previous studies suggest that genetic intervention in SHANK3-related ASD may be most effective earlier in development.

A mouse model and previous studies suggest that genetic intervention in SHANK3-related ASD may be most effective earlier in development.A mouse study by Craig Powell, M.D., Ph.D., and colleagues suggests that early genetic rescue may be a potential therapy in autism spectrum disorder, or ASD. Powell looked at one gene called SHANK3, whose alteration is seen in about 0.5 percent of ASD patients.

The study is published in eNeuro and was highlighted on the ASD news site Spectrum. Powell is professor and chair of the Department of Neurobiology at the University of Alabama at Birmingham and also heads the UAB Civitan International Research Center. The UAB researcher has a longstanding focus on autism, intellectual disability and cognitive dysfunction.

The SHANK3 gene product acts in the brain as a postsynaptic scaffolding protein. A synapse is a gap between two nerve cells where a signal is passed from one nerve to the other. A human brain may have more than 100 trillion synapses in its neuronal circuitry.

Powell and colleagues previously showed that mice deficient in SHANK3 protein have behavioral abnormalities, including repetitive grooming and deficits in social interaction, locomotor activity and rearing. Rearing is standing on hind legs to investigate the surroundings. Some of these behaviors are reminiscent of ASD in humans, which is characterized by deficits in social interaction and communication, restricted interests and repetitive behaviors.

Powells lab and other labs, including Guoping Feng, Ph.D., Massachusetts Institute of Technology, have sought mouse models where a SHANK3 deficit could be reversed early or later in life, to see if that reversal removed some of the behavioral deficits. Powell says his and Fengs labs used different experimental approaches, and their two studies are complementary.

Powells lab used genetic tools to construct mice that had a stop signal inserted into one or both genes for SHANK3, creating heterozygous or homozygous mice for the mutation they call ShankE13. The activation of another inserted gene called Cre-recombinase can excise that stop signal, restoring full function of the mutated SHANK3 gene.

In Fengs mouse model, the SHANK3 gene was activated when the mice were given tamoxifen, which leads to some toxicity, including weight loss. In the Powell mouse model, the Cre-recombinase was negatively controlled by the antibiotic doxycycline; as long as mice were fed doxycycline, the Cre-recombinase was supposed to be shut off. When the doxycycline is stopped, the SHANK3 gene should be restored. Another genetic in the mouse model was supposed to limit reactivation of the SHANK3 gene to the striatum and cerebellum of the brain.

The plan was to activate the Cre-recombinase at different ages and test those mice for changes in ASD-like behaviors.

This elegant approach had two problems, the researchers learned. First, there was more widespread rescue of the SHANK3 gene in the brain than expected, including in the cortex. Second, the doxycycline control was leaky, allowing expression of the Cre-recombinase even as the mice were fed the antibiotic. Thus, Powell and colleagues were only able to look at the effect of early developmental genetic reversal of ShankE13, occurring about embryonic day 18.

Still, as Powell told Spectrum, It is important to publish experiments that do not work out exactly as planned.

Craig Powell, M.D., Ph.D.In a wide variety of behavioral tests, the researchers found that early genetic restoration of SHANK3 rescued a variety of behaviors that included repetitive grooming and social, locomotor, and rearing deficits.

The social tests included the amount of social interaction with another mouse; social recognition memory, where a test mouse was introduced to another mouse, and then reintroduced three days later; and social novelty exploration, which compares the amount of time spent with a novel caged mouse versus an inanimate object.

The locomotor tests included placing mice in a novel cage with minimal bedding and measuring how much they freely explored over two hours. In a different series of tests, the mice as expected showed no changes in anxiety-related behaviors. That lack of change in anxiety in mutant and rescued mice had also been shown in previous work.

Overall, Powell said, our studies suggest early genetic rescue as a potential genetic therapy for ASD-like behaviors in ASD associated with SHANK3 deletion or mutation. Taken together with previously published studies, genetic intervention in SHANK3-related ASD may be most effective earlier in development.

Co-authors with Powell for the study, Early restoration of Shank3 expression in Shank3 knockout mice prevents core ASD-like behavioural phenotypes, are Thomas C. Jaramillo, Jeremy M. Reimers, Christine O. Escamilla and Shunan Liu, University of Texas Southwestern Medical Center, Dallas; and Zhong Xuan, UAB Department of Neurobiology.

Powell moved to UAB from the Southwestern Medical Center in 2018. At UAB, Powell holds the Virginia B. Spencer Endowed Professorship in Neuroscience.

Support came from National Institutes of Health grants HD069560 and HD069560-S1, Autism Speaks, an Autism Science Foundation Pre-doctoral Fellowship, The Hartwell Foundation, gifts from Clay Heighten and Debra Caudy, and BRAINS for Autism.

Originally posted here:
Genetic rescue of SHANK3 is potential therapy in rare forms of autism spectrum disorder - The Mix