New research from The University of Manchester published in the Journal of Community Genetics reveals a stark variation in genetic testing services for inherited eye disease in England.

The study, which was part-funded by Fight for Sight, shows that service provision in the North-east is much lower than expected based on population size and demographics, while in London and the South-east, it's much higher.

Genetic tests have been available on the NHS for over a decade for a limited number of inherited retinal dystrophies such as retinitis pigmentosa. However, new technology, known as 'next-generation sequencing' (NGS), has made it possible to map many genes simultaneously, saving time and money.

NGS means that many more patients with inherited retinal dystrophies could receive accurate genetic diagnoses and appropriate genetic counselling on how the condition might affect their families. But in order to plan for an expansion in NHS service provision, it is necessary to know how well existing services are working.

In the current study, the research team looked back at genetic testing in 2003-2011 for common mutations in six genes linked to dominantly inherited and X-linked retinitis pigmentosa. They quantified the variation in testing rate between the nine NHS regions in England, based on population size and demographics.

Results showed that by 2011, 4.5 per 100,000 males and 2.6 per 100,000 females in England had been tested. However, there was a wide variation in testing rates between the regions.

In north-east England there were approximately half as many tests as expected, whereas in the south-east, the rate was over a third more than expected. Only in the west Midlands and east England were test rates in line with the overall rate for England.

"It is likely that a number of factors have contributed to this variation in access to genetic services," said Professor Graeme Black from the Centre for Genomic Medicine at The University of Manchester, who led the research. "For instance, the at-risk population is not uniform across England; the way in which diagnostic tests are made available to clinicians varies between regions; and it's unclear whether there is variation in the way that clinicians and genetic counsellors explain the tests to patients.

"However, it is clear that we are unlikely to achieve equal access across the regions by chance. We need a consistent approach in providing information to patients about the availability and perceived value of testing and we need a strong evidence base to support the value of genetic testing on grounds of clinical and economic utility.

"In this way we can begin to develop a single, national strategy that will make it possible to fulfil the huge potential of next-generation sequencing to improve patient care and drive research forward."

Go here to read the rest:

South-east England ahead on genetic tests for inherited eye conditions

DNA sequencing and synthesis are two sides of the same coin, the read and write functions of genetic material. The field and its requisite technology took off in the 1990s with the Human Genome Projects effort to sequence billions of bases and unlock a new era of genetically informed medicine. The resulting science is still a work in progress it turns out the genetic code is more complicated than anticipated but the technologies and companies it helped spawn are an impressive legacy.

Integrated DNA Technologies (IDT) got its start during the Human Genome Project, as it produced single nucleotides (the As, Ts, Cs, and Gs that comprise the genetic code) and short oligonucleotide chains (or oligos) to help facilitate a massive sequencing effort around the world. Of course, sequencing technology has advanced dramatically in the intervening decades, but you still need oligos to do the sequencing, explains Jerry Steele, IDTs Director of Marketing, especially in the next gen sequencing space. Sequencing and DNA synthesis go hand in hand.

The current sequencing method of choice is Illumina, a process that frequently returns millions of bases of DNA sequence by reading distinct stepwise fluorescent signals associated with each base in a massively parallel array. To distinguish genetic material from different samples (a few hundred are often run on the same plate), scientists label each samples DNA extract with a distinct barcode. With each barcode comprised of about ten nucleotides, the demand for synthetic DNA chains in the sequencing process is substantial.

Unlike other biotech companies prioritizing longer constructs or gene variants, IDT specializes in relatively short oligos. These chains are used not only in Illumina barcoding, but also as primers consistent patches of sequence that may border unknown regions and facilitate PCR-based amplification. Both techniques next gen Illumina sequencing and primer-based amplification are staples of any self-respecting applied or research-based microbiology laboratory, as they allow researchers to identify constituent organisms or confirm a genes presence.

With such short sequences, a single nucleotide discrepancy could mean the difference between two Illumina samples from opposite ends of the world, or between a gene native to the Firmicutes or the Proteobacteria. Its a small margin for error, so every base better be right, explains Steele. As weve grown, its just a matter of maintaining that consistency on a larger scale. In the spirit of not fixing something that needs no repairs, IDT shipped an entire fabrication room from its headquarters in Des Moines to Belgium when that facility was being built.

Fundamental as they are to modern biology, oligos are used every day in thousands of laboratories around the world, often in innovative ways that the company itself may not have predicted. The things that people are doing with DNA are really inspiring, notes Steele. One of his favorite use cases involves low-impact prenatal tests: rather than a painful and invasive amniosyntesis, weve discovered that now because of sequencing, we can see the babys DNA in a blood draw from the mother. Improved sequencing fidelity and throughput are expanding the resolution of the technique, and Steele soon envisions scientists using next gen sequencing to detect cancer cells from the blood stream as an early diagnosis tool. Biology is really leaving the lab and coming into the real world, Steele explains, and its going to improve a lot of lives.

*This article is part of a special series on DNA synthesis and was previously published at SynBioBeta, the activity hub for the synthetic biology industry.

Excerpt from:

Short and Sweet: Why Modern Molecular Biology Needs Oligos

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Newswise Boston (March 31, 2015) Coronary heart disease and stroke, two of the leading causes of death in the United States, are diseases associated with heightened platelet reactivity. A new study in humans suggests an underlying reason for the variability in the risk of clotting is due to a genetic variation in a receptor on the surface of the platelet. Additionally, the current study suggests that people expressing this genetic variant may be less protected from clotting and thrombosis when taking current anti-platelet therapies such as Aspirin and other blood thinning medications.

Antiplatelet therapy has helped to drastically reduce mortality associated with heart attacks and strokes; however, some individuals taking antiplatelet drugs are not fully protected from platelet clot formation. For example, black individuals are disproportionately burdened by these diseases compared to white individuals even after adjusting for clinical and demographic factors.

Benjamin Tourdot, Ph.D., a Postdoctoral Fellow on a research team led by Michael Holinstat, Ph.D., at the University of Michigan Department of Pharmacology recently discovered a genetic variant in a key platelet receptor, PAR4, which enhances platelet reactivity and is more frequently expressed in blacks than whites. The research will be presented at the American Society for Pharmacology and Experimental Therapeutics (ASPET) Annual Meeting during Experimental Biology 2015.

While the genetic variation is more common in blacks than whites it is still relatively common in both races with 76 percent of blacks and 36 percent of whites expressing at least one copy of the gene responsible for the hyper-responsiveness.

To determine if individuals with the hyper-responsive form of PAR4 may be less protected following a myocardial infarction or stroke even after receiving recommended antiplatelet therapy, the investigators compared healthy individuals and cardiac patients with and without the mutation for their responsiveness to PAR4 who were taking standard of care antiplatelet therapy (Aspirin and Plavix). The preliminary data demonstrated that independent of race individuals with a copy of the hyperactive variant of PAR4 have an increase in PAR4-mediated platelet reactivity compared to individuals without the variant even in the presence of antiplatelet therapy.

This work could identify the PAR4 T120A variant as a potential risk factor for thrombosis, and would require a new approach to treating patients with this genetic variant including the development of PAR4 antagonists.

A greater understanding of which patients benefit the most from current therapeutic strategies and which patients remain at elevated risk for a thrombotic event will aid in the development of new therapeutic targets for at-risk populations.

This study reinforces the personalized medicine approach to therapeutic intervention and challenges the one size fits all approach, which often leaves at risk populations without adequate protection from thrombotic events and stroke.

The rest is here:

Genetic Variability in the Platelet Linked to Increased Risk for Clotting

The ACMG Foundation for Genetic and Genomic Medicine announces the first recipient of the ACMG Foundation Carolyn Mills Lovell Award at the 2015 ACMG Annual Clinical Genetics Meeting in Salt Lake City, Utah: First award specifically for genetic counselors

Stephanie Harris, CGC was honored as the first recipient of the ACMG Foundation Carolyn Mills Lovell Award at the American College of Medical Genetics and Genomics (ACMG) 2015 Annual Clinical Genetics Meeting in Salt Lake City, Utah.

Ms. Harris was selected to receive the award for her poster presentation, "The Impact of Variant Reclassification on Hypertrophic Cardiomyopathy Research".

Ms. Harris completed her Masters of Science in Human Genetics and Genetic Counseling at Stanford University School of Medicine in Stanford, CA. and her Bachelor of Science in Biology at Bucknell University in Lewisburg, PA. She is currently a genetic counselor in Cardiovascular Genetics at Brigham and Women's Hospital in Boston, MA.

This award was made possible due to a generous donation by ACMG Medical Director David Flannery, MD, FAAP, FACMG to honor genetic counselor Carolyn Mills Lovell, MAT, MS, CGC. Dr. Flannery worked with Ms. Lovell for over 15 years while he was at the Medical College of Georgia (MCG) of Georgia Regents University, and wanted to recognize the contributions and accomplishments of genetic counselors through this award. This award includes a cash prize of $1000 and will be presented to one recipient annually through 2025.

"I wanted to help recognize genetic counselors who play a huge role in clinical genetic services and felt that this award would help with that and also honor Carolyn, who has always provided exemplary services to families, students and residents at MCG " said ACMG Medical Director David Flannery, MD, FAAP, FACMG.

ACMG Foundation President Bruce R. Korf, MD, PhD, FACMG added, "It is exciting to see the ACMG Foundation offer an award intended specifically for genetic counselors. Genetic counselors are integral members of the genetics care team and their role is expanding in this era of genomic medicine. I am very pleased to see the contribution of genetic counselors recognized through this award."

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The ACMG Foundation for Genetic and Genomic Medicine, a 501(c)(3) nonprofit organization, is a community of supporters and contributors who understand the importance of medical genetics in healthcare. Established in 1992, the ACMG Foundation for Genetic and Genomic Medicine supports the American College of Medical Genetics and Genomics; mission to "translate genes into health" by raising funds to attract the next generation of medical geneticists and genetic counselors, to sponsor important research, to promote information about medical genetics, and much more.

To learn more about the important mission and projects of the ACMG Foundation for Genetic and Genomic Medicine and how you too can support this great cause, please visit http://www.acmgfoundation.org or contact us at acmgf@acmgfoundation.org or 301/718-2014.

Originally posted here:

ACMG Foundation announces inaugural recipient of Lovell Award

PACK360@USC Institute for Genetic Medicine Art Gallery
PACK360 has taken an architectural approach to building art. Each site specific piece is layered in construction in a similar process to building a wall. The intention is to extend geometry...

By: Pat Giles

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PACK360@USC Institute for Genetic Medicine Art Gallery - Video

By Dennis Thompson HealthDay Reporter

WEDNESDAY, March 25, 2015 (HealthDay News) -- Researchers say they've discovered a new genetic cause of autism, singling out a rare gene mutation that appears to hamper normal brain development early on in powerful ways.

The gene, CTNND2, provides instructions for making a protein called delta-catenin, which plays crucial roles in the nervous system, said senior author Aravinda Chakravarti, a professor in the Johns Hopkins University School of Medicine's Institute of Genetic Medicine.

His research team found that a group of girls with severe autism carried CTNND2 mutations that appeared to reduce the effectiveness of delta-catenin, potentially affecting their neurological development.

"There are many, many proteins that in fact 'moonlight,' doing many, many different things," Chakravarti said. "Maybe the severity of the effect of delta-catenin comes from the fact that when you lose function of this protein, you lose not just one function but many functions. Although that remains to be shown, it is strongly implicated by our study."

Autism spectrum disorder is a neurological and developmental disorder that begins early in life. The cause is not known, although scientists suspect genes play a role.

The researchers discovered the CTNND2 gene's link to autism using an approach that focuses on rare and extreme cases of autism, according to the study released online March 25 in the journal Nature.

By focusing on extreme cases, they believe they will discover genes that have a more powerful effect on brain development and help explain the root causes of autism.

"If we study rare and extreme forms, they are both genetic and they represent very early neurodevelopmental events," Chakravarti said.

The researchers chose to study girls with autism because they are far less likely to have autism than boys. When girls do develop the disorder, their symptoms tend to be severe.

More:
Scientists Spot Gene Tied to Severe Autism in Girls

Its the most complete genetic map of an entire country yet completed and it could show clues of what medicine could look like in the coming age of big data.

Researchers working at DeCode Genetics, a unit of the drug company Amgen, have sequenced the genomes of 2,636 Icelanders and used genealogical records and more spotty genetic data to calculate the likely genetics of 101,584 more. Because DeCode has anonymized access to patient medical records, the company could then look for relationships between the genetic variants and disease and they found a new genetic variant that increases the risk of Alzheimers, as well as confiming suspected variants that raise the risk of diabetes and one that causes atrial fibrillation, a heart condition. The results are published in three scientific papers in the journal Nature.

Its certainly an impressive tour de force, says George Yancopoulos, the Chief Scientific Officer of Amgen rival Regeneron. This is certainly establishing a benchmark for all of us and showing the value of this type of analysis, in particular in the Icelandic population.

Regeneron is creating its own database of sequencing data with Pennsylvanias Geisinger Health Systems. The United Kingdom has embarked on a 100,000 Genomes Project. And President Obama has proposed linking together lots of ongoing sequencing projects into a database of 1 million volunteers. The DeCode experiment, started 18 years ago during the dot-com boom, is our first look at the kind of data that these gargantuan efforts could produce.

Some important basic science questions were answered. For instance, a lot of effort is put into figuring out when the most recent common male ancestor of all people has lived, an area of research that could be important for understanding of diseases linked to the (male) Y chromosome. But Amgen bought DeCode, and its access to Icelands population for $415 million two years ago. It didnt spend that kind of coin to find out about the mutation rate on the Y chromosome.

The hope has always been that these kinds of genetic data would lead to new drugs. And DeCode provides a series of huge leads. Scientists frequently try to figure out what genes do by knocking them out (that is, breaking them) in mice. Doing the same experiment in humans would be, of course, highly unethical.

Except that some people are born with naturally dysfunctional copies of some genes. And these can be clues to drugs. Theres even a great example: having a dysfunctional version of a gene called PCSK9 results in lower cholesterol levels and rates of heart disease. There are even people with two broken copies of the gene, including an aerobics instructor in Dallas who has levels of LDL, or bad cholesterol, of 14 milligrams per deciliter, compared to normal levels of more than 100 mg/dL.

Both Amgen and Regeneron have drugs (evolocumab and alirocumab) that block PCSK9 that will soon hit the market, in what is expected to be one of the most heated drug launches in years. Drug company executives hope that more genetic data would mean finding more genes like PCSK9 that could be useful drug targets.

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In A Genetic Portrait Of A Nation, A Map Of The Future

Using a novel approach that homes in on rare families severely affected by autism, a Johns Hopkins-led team of researchers has identified a new genetic cause of the disease. The rare genetic variant offers important insights into the root causes of autism, the researchers say. And, they suggest, their unconventional method can be used to identify other genetic causes of autism and other complex genetic conditions.

A report on the study appears in the April 2 issue of the journal Nature.

In recent years, falling costs for genetic testing, together with powerful new means of storing and analyzing massive amounts of data, have ushered in the era of the genomewide association and sequencing studies. These studies typically compare genetic sequencing data from thousands of people with and without a given disease to map the locations of genetic variants that contribute to the disease. While genomewide association studies have linked many genes to particular diseases, their results have so far failed to lead to predictive genetic tests for common conditions, such as Alzheimer's, autism or schizophrenia.

"In genetics, we all believe that you have to sequence endlessly before you can find anything," says Aravinda Chakravarti, Ph.D. , a professor in the Johns Hopkins University School of Medicine's McKusick-Nathans Institute of Genetic Medicine. "I think whom you sequence is as important -- if not more so -- than how many people are sequenced."

With that idea, Chakravarti and his collaborators identified families in which more than one female has autism spectrum disorder, a condition first described at Johns Hopkins in 1943. For reasons that are not understood, girls are far less likely than boys to have autism, but when girls do have the condition, their symptoms tend to be severe. Chakravarti reasoned that females with autism, particularly those with a close female relative who is also affected, must carry very potent genetic variants for the disease, and he wanted to find out what those were.

The research team compared the gene sequences of autistic members of 13 such families to the gene sequences of people from a public database. They found four potential culprit genes and focused on one, CTNND2, because it fell in a region of the genome known to be associated with another intellectual disability. When they studied the gene's effects in zebrafish, mice and cadaveric human brains, the research group found that the protein it makes affects how many other genes are regulated. The CTNND2 protein was found at far higher levels in fetal brains than in adult brains or other tissues, Chakravarti says, so it likely plays a key role in brain development.

Specifically, mutations in CNNTD2 disrupted the connections called synapses that form among brain cells. "This is consistent with recent findings that many gene mutations associated with autism are involved in synapse development," says Richard Huganir, Ph.D. , director of the Solomon H. Snyder Department of Neuroscience, who participated in the research. "The results of this study add to the evidence that abnormal synaptic function may underlie the cognitive defects in autism."

While autism-causing variants in CTNND2 are very rare, Chakravarti says, the finding provides a window into the general biology of autism. "To devise new therapies, we need to have a good understanding of how the disease comes about in the first place," he says. "Genetics is a crucial way of doing that."

Chakravarti's research group is now working to find the functions of the other three genes identified as possibly associated with autism. They plan to use the same principle to look for disease genes in future studies of 100 similar autism-affected families, as well as other illnesses. "We've shown that even for genetically complicated diseases, families that have an extreme presentation are very informative in identifying culprit genes and their functions -- or, as geneticists are taught, 'treasure your exceptions.'" Chakravarti says.

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New autism-causing genetic variant identified

Patricia L. Hall, Ph.D., FACMG of Emory University is the recipient of the 2015 Richard King Trainee Award for the best publication in ACMG's academic journal, Genetics in Medicine

Patricia L. Hall, PhD, FACMG of Emory University is the recipient of the 2015 Richard King Trainee Award. This award was instituted by the ACMG Foundation for Genetic and Genomic Medicine to encourage ABMGG, international equivalents or genetic counseling trainees in their careers and to foster the publication of the highest quality research in ACMG's peer-reviewed journal, Genetics in Medicine (GIM).

Each year the editorial board reviews all articles published in GIM by an ABMGG or genetic counseling trainee who was either a first or corresponding author during that year. The manuscript considered to have the most merit is selected by the editorial board and a cash prize, along with meeting expenses, is awarded at the 2015 ACMG Annual Clinical Genetics Meeting in Salt Lake City, Utah.

Dr. Hall was given the award for her manuscript titled, "Postanalytical tools improve performance of newborn screening by tandem mass spectrometry" which was published in the December 2014 issue of Genetics in Medicine. The corresponding author was Piero Rinaldo, MD, PhD, FACMG of the Mayo Clinic. Dr. Hall is currently a Director in the Biochemical Genetics Laboratory at Emory University, "It is an honor to have the hard work and dedication of everyone involved with our newborn screening paper recognized with the Richard King Trainee Award for best publication."

The award is given by the ACMG Foundation and is named for Dr. Richard King in recognition of his instrumental role in creating Genetics in Medicine and serving as the first and founding Editor-in-Chief of the journal.

Eligible trainees include those in the following programs: Clinical Biochemical Genetics; Clinical Cytogenetics; Clinical Molecular Genetics Combined Internal Medicine/Genetics; Combined Pediatrics/Genetics; PhD Medical Genetics and Genetic Counseling.

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The ACMG Foundation for Genetic and Genomic Medicine, a 501(c)(3) nonprofit organization, is a community of supporters and contributors who understand the importance of medical genetics and genomics and genetic counseling in healthcare. Established in 1992, the ACMG Foundation supports the American College of Medical Genetics and Genomics' mission to "translate genes into health" by raising funds to promote the profession of medical genetics and genomics to medical students, to fund the training of future medical geneticists, to support best-practices and tools for practicing physicians and laboratory directors, to promote awareness and understanding of our work in the general public, and much more.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Original post:

Patricia Hall, Ph.D., earns 2015 King Trainee Award for best publication, Genetics in Medicine

Photo: Chris Lund The blood of a thousand Icelanders.

When the first Viking explorers began settling Iceland, none could have imagined that theirdescendants would pioneer thefuture of modern medicine by surveying the human genome. Fast forward 1000 years to today, whenanIcelandic company has revealedits success insequencing the largest-ever set of human genomes from a single population. The new wealth of genetic data has already begunchanging our understanding of human evolutionary history. It also sets the stage for a new era of preventive medicinebased on individual genetic risks fordiseases such as cancer and Alzheimers disease.

Themilestone in genome sequencing comesfromdeCODE Genetics, a biopharmaceutical company inReykjavk, Iceland. Theirwork, published as four papers in the 25 March 2015 issue of the journalNature Genetics,has yielded new insights aboutthecommon human ancestor for the male Y chromosomenarrowed tosomewhere between 174,000 and 321,000 years agobased on their latest calculation of human mutation rates. Another part of their work discovered thatabout 7.7 percent of the modern-day population has rare knockout genesgenes that have beendisabled by mutations. Early research has also revealed a mutation in theABCA7gene,whichdoubles the risk of Alzheimers disease in Iceland and other populations dominated by European ancestry.

These are just a handful of observations that have come out of the ability to look at the sequence of the genome of an entire nation,saidKari Stefansson, founder of deCODE Genetics, during a press briefing onMonday, 23 March.What is more, we are now sitting in Iceland with the possibility of taking advantage of these insights when it comes to the Icelandic healthcare system.

The company sequenced thewhole genomes of 2636 Icelanders and used those genomes as the basis for calculatingthe genetic variances for the entire Icelandic population.Iceland represents a unique laboratory for genetics researchers because much of the modern population traces its lineage to a relatively small number of founders; a fact that makes it easier to trace genealogies and pedigrees.

Myles Axton, chief editor ofNature Genetics, introduced the Monday press briefingbydescribing how the genetic sequencing strategy in Iceland could also work for other countries:

This strategy of sequencing the DNA of about 1 in 100 of the population, a total of 2,636 Icelanders, and then using shared sets of common genetic variance to predict the full spectrum of genetic variance carried by the whole population, is a great model for the future of human genetics. This technique can be applied to any population and is all the more accurate when there are pedigrees available for much of the population.

Genome sequencing has alloweddeCODE Genetics to begin data-mining information about how certain genes function and their relationship to a broad array of diseases. Past findings from such research included additional insights about gene variants associated with Alzheimers disease and schizophrenia.

The growing database on knockout genes may prove particularly helpful when matched against the phenotypes of individualsthe physical traits or characteristics that can be observed. Perhaps unsurprisingly, the researchers found that knockouts are least common among genes expressed in the brain, given that organs importance.

Basically what we hope to get out of phenotyping the carriers of these knockouts is to figure out which biochemical pathways are necessary for which physiological functions, Stefansson explained.Then the question is whetherthere is redundancy in some of these physiological functions;are there alternative biochemical pathways that can compensate for the loss of one?

Go here to read the rest:

Iceland's Giant Genome Project Points to Future of Medicine

Its the most complete genetic map of an entire country yet completed and it could show clues of what medicine could look like in the coming age of big data.

Researchers working at DeCode Genetics, a unit of the drug company Amgen, have sequenced the genomes of 2,636 Icelanders and used genealogical records and more spotty genetic data to calculate the likely genetics of 101,584 more. Because DeCode has anonymized access to patient medical records, the company could then look for relationships between the genetic variants and disease and they found a new genetic variant that increases the risk of Alzheimers, as well as confiming suspected variants that raise the risk of diabetes and one that causes atrial fibrillation, a heart condition. The results are published in three scientific papers in the journal Nature.

Its certainly an impressive tour de force, says George Yancopoulos, the Chief Scientific Officer of Amgen rival Regeneron. This is certainly establishing a benchmark for all of us and showing the value of this type of analysis, in particular in the Icelandic population.

Regeneron is creating its own database of sequencing data with Pennsylvanias Geisinger Health Systems. The United Kingdom has embarked on a 100,000 Genomes Project. And President Obama has proposed linking together lots of ongoing sequencing projects into a database of 1 million volunteers. The DeCode experiment, started 18 years ago during the dot-com boom, is our first look at the kind of data that these gargantuan efforts could produce.

Some important basic science questions were answered. For instance, a lot of effort is put into figuring out when the most recent common male ancestor of all people has lived, an area of research that could be important for understanding of diseases linked to the (male) Y chromosome. But Amgen bought DeCode, and its access to Icelands population for $415 million two years ago. It didnt spend that kind of coin to find out about the mutation rate on the Y chromosome.

The hope has always been that these kinds of genetic data would lead to new drugs. And DeCode provides a series of huge leads. Scientists frequently try to figure out what genes do by knocking them out (that is, breaking them) in mice. Doing the same experiment in humans would be, of course, highly unethical.

Except that some people are born with naturally dysfunctional copies of some genes. And these can be clues to drugs. Theres even a great example: having a dysfunctional version of a gene called PCSK9 results in lower cholesterol levels and rates of heart disease. There are even people with two broken copies of the gene, including an aerobics instructor in Dallas who has levels of LDL, or bad cholesterol, of 14 milligrams per deciliter, compared to normal levels of more than 100 mg/dL.

Both Amgen and Regeneron have drugs (evolocumab and alirocumab) that block PCSK9 that will soon hit the market, in what is expected to be one of the most heated drug launches in years. Drug company executives hope that more genetic data would mean finding more genes like PCSK9 that could be useful drug targets.

Read more:

Amgen Releases A Giant Genetic Portrait Of A Nation -- And A Map Of The Future

Irvine, CA (PRWEB) March 25, 2015

Proove Biosciences, a commercial and research leader in Personalized Medicine, is excited to announce the success of their commercially supported symposium, Personalized Medicine: Incorporating Genetic Testing to Optimize the Management of Pain, at the 31st Annual American Academy of Pain Medicine conference in National Harbor, Maryland on Thursday, March 19th, 2015.

The symposiums faculty, which consisted of former AAPM President Lynn Webster, M.D., former Florida Society of Interventional Pain Physicians President Sanford Silverman, M.D., and local D.C. pain physician Abraham Cherrick, M.D. presented supporting data for Prooves proprietary genetic tests; tests that are designed to objectively guide clinical decisions in screening for opioid contraindications, improve medication efficacy, and avoid adverse drug events.

Most people don't realize the tremendous variability people have to the same painful stimulus. This is why some people hurt while other don't seem to be bothered by the same type of trauma. states Lynn Webster, M.D. It is now clear that pain sensitivity is significantly influenced by our genes. Scientist are able to identify pain reducing genes and pain elaboration genes.

Webster, M.D. continues, Although it is only an emerging field it is exciting because genotyping may allow us to identify people who are more likely to respond to one drug than another. Even more importantly, genotyping offers potential to identify individuals who may have side effects or toxicity to certain drugs. This means genetic testing can lead to safer and more effective therapy. Personalized medicine uses genetic testing to optimize pain management and many other areas in medicine.

About Proove Biosciences Our Mission is to Change the Future of Medicine. Proove is the proof to improve healthcare decisions. We seek to realize a future when clinicians look back and wonder how they couldve ever prescribed medications without knowing how a patient would respond. With offices in Southern California and the Baltimore-Washington metropolitan area, the Company is the research leader investigating and publishing data on the genetics of personalized pain medicine with clinical research sites across the United States. Physicians use Proove Biosciences testing to improve outcomes both safety and efficacy of medical treatment. From a simple cheek swab collected in the office, Proove performs proprietary genetic tests in its CLIA-certified laboratory to identify patients at risk for misuse of prescription pain medications and evaluate their metabolism of medications. For more information, please visit http://www.proove.com or call toll free 855-PROOVE-BIO (855-776-6832).

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Proove Biosciences Hosts Symposium on Incorporating Genetic Testing to Optimize the Management of Pain

David Paul Morris/Bloomberg via Getty

Cloud processing of DNA sequence data promises to speed up discovery of disease-linked gene variants.

The dream for tomorrows medicine is to understand the links between DNA and disease and to tailor therapies accordingly. But scientists working to realize such personalized or precision medicine have a problem: how to keep genetic data and medical records secure while still enabling the massive, cloud-based analyses needed to make meaningful associations. Now, tests of an emerging form of data encryption suggest that the dilemma can be solved.

At a workshop on 16 March hosted by the University of California, San Diego (UCSD), cryptographers analysed test genetic data. Working with small data sets, and using a method known as homomorphic encryption, they could find disease-associated gene variants in about ten minutes. Despite the fact that computers were still kept bogged down for hours by more-realistic tasks such as finding a disease-linked variant in a stretch of DNA a few hundred-thousandths the size of the whole genome experts in cryptography were encouraged.

This is a promising result, says Xiaoqian Jiang, a computer scientist at UCSD who helped to set up the workshop. But challenges still exist in scaling it up.

Physicians and researchers think that understanding how genes influence disease will require genetic and health data to be collected from millions of people. They have already started planning projects, such as US President Barack Obamas Precision Medicine Initiative and Britains 100,000 Genomes Project. Such a massive task will probably require harnessing the processing power of networked cloud computers, but online security breaches in the past few years illustrate the dangers of entrusting huge, sensitive data sets to the cloud. Administrators at the US National Institutes of Healths database of Genotypes and Phenotypes (dbGaP), a catalogue of genetic and medical data, are so concerned about security that they forbid users of the data from storing it on computers that are directly connected to the Internet.

Homomorphic encryption could address those fears by allowing researchers to deposit only a mathematically scrambled, or encrypted, form of data in the cloud. It involves encrypting data on a local computer, then uploading that scrambled data to the cloud. Computations on the encrypted data are performed in the cloud and an encrypted result is then sent back to a local computer, which decrypts the answer. If would-be thieves were to intercept the encrypted data at any point along the way, the underlying data would remain safe.

If we can show that these techniques work, then it will give increased reassurance that this high-volume data will be computed on and stored in a way that protects individual privacy, says Lucila Ohno-Machado, a computer scientist at UCSD and a workshop organizer.

Homomorphic data encryption, first proposed in 1978, differs from other types of encryption in that it would allow the cloud to manipulate scrambled data in essence, the cloud would never actually see the numbers it was working with. And, unlike other encryption schemes, it would give the same result as calculations on unencrypted data.

But it remained largely a theoretical concept until 2009, when cryptographer Craig Gentry at the IBM Thomas J. Watson Research Center in Yorktown Heights, New York, proved that it was possible to carry out almost any type of computation on homomorphically encrypted data. This was done by transforming each data point into a piece of encrypted information, or ciphertext, that was larger and more complex than the original bit of data. A single bit of unencrypted data would become encrypted into a ciphertext of a few megabytes the size of a digital photograph. It was a breakthrough, but calculations could take 14 orders of magnitude as long as working on unencrypted data. Gentry had rendered the approach possible, but it remained impractical.

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Extreme cryptography paves way to personalized medicine

Scientists have found that genetic changes in bowel tumours are linked to the way the body's immune system responds to the cancer, according to research published today (Monday) in the journal Oncoimmunology*.

For the first time, Cancer Research UK researchers at the University of Birmingham have found that certain genetic flaws in bowel cancer are more likely to trigger an immune response at the site of tumours, meaning that treatments to boost this immune response further could potentially be helpful for these patients.

Finding out what's happening in a cancer patient's immune system can be difficult and takes time. These findings suggest that genetic profiles of patients' tumours could be used as an easy and fast way of diagnosing whether they are suitable for immunotherapy treatments, and if so which ones.

Cancer Research UK's FOCUS4** trial is already using the genetics of bowel cancer to offer patients stratified medicine and this study suggests that we could further expand this work to include immunotherapies.

Gary Middleton, Professor of Medical Oncology at the School of Cancer Sciences at the University of Birmingham, said: "The field of immunotherapy is gaining lots of momentum and this study shows a new finding for bowel cancer. We are already using genetic profiling for stratified medicine in bowel cancer in the FOCUS4 trial. But this research indicates that we could marry immunotherapy with the work we are already doing to personalise treatment even more."

Researchers used The Cancer Genomic Atlas, a large database, to study this relationship. From this research, scientists can now start looking at what causes a weak immune response and in the future, could target drugs to switch off the immune suppression associated with certain genetic mutations.

Nell Barrie, senior science communication manager at Cancer Research UK, said: "This study shows a strong association between certain genetic profiles and immune responses, but we don't yet fully understand this link. Further research to investigate the fundamentals behind different immune responses could open new doors in drug development."

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For media enquiries contact Stephanie in the Cancer Research UK press office on 020 3469 5314 or, out of hours, on 07050 264 059.

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New potential for personalized treatments in bowel cancer

How to get the right treatment to the right patient at the right time

University of Glasgow leads the way in new global drug treatments

The University of Glasgow is launching the first ever Masters programme designed to specifically address the new paradigm in drug discovery stratified medicine which tailors drug therapies to individual patients genetic makeup.

The University of Glasgow is at the forefront of stratified medicine, which involves examining the genetic makeup of patients and their differing responses to drugs designed to treat specific diseases the right treatment to the right patient at the right time.

The course director of the new MSc in Clinical Trials and Stratified Medicine, Professor Matthew Walters, said: Stratified Medicine holds huge potential in the timely development of new treatments for human disease. It is among the most important concepts to emerge in 21stcentury clinical science and will be a crucial component of the global drive to increase the efficacy, safety and cost-effectiveness of new treatments.

He added: There has been global recognition of the need for training in this area so that we have young drug researchers in academia and the commercial environment imbued with the skills required to apply the science for the benefit of patients.

Glasgow is also home to the Stratified Medicine Scotland Innovation Centre, which combines cutting-edge genetic research with state-of-the-art health informatics and imaging technologies. It is a unique collaboration in healthcare between partners from academia, the NHS and the pharmaceutical industry.

There is already huge interest in stratified medicine and pharmaceutical science in Saudi Arabia, said Professor Walters.

China also has a nascent clinical trials industry and Professor Walters is keen to involve Chinese students and academics in this area.

One of the elements we need to be clear about is whether medicines have the same impact across different populations. People handle drugs differently in different parts of the globe. There will be a significant need for people in China with these skills to be running clinical trials over the next few decades, he said.

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University of Glasgow leads the way in drug treatments

Photo: Andrew Brookes/Corbis

In 2005, next-generation sequencing began to change the field of genetics research. Obtaining a persons entire genome became fast and relatively cheap. Databases of genetic information were growing by the terabyte, and doctors and researchers were in desperate need of a way to efficiently sift through the information for the cause of a particular disorder or for clues to how patients might respond to treatment.

Companies have sprung up over the past five years that are vying to produce the first DNA search engine. All of them have different tacticssome even have their own proprietary databases of genetic informationbut most are working to link enough genetic databases so that users can quickly identify a huge variety of mutations. Most companies also craft search algorithms to supplement the genetic information with relevant biomedical literature. But as in the days of the early Web, before Google reigned supreme, a single company has yet to emerge as the clear winner.

Making a functional search engine is a classic big-data problem, says Michael Gonzalez, the vice president of bioinformatics at one such company, ViaGenetics, which was expected to relaunch its platform in March. Before doctors or researchers can use the data, genomic data must be organized so that humans can read and search it. The first step toward that is to put it in a standard form called the variant call format, or VCF. As raw data, a persons complete sequenced genome would take up about 100 gigabytes, so a database that adds the genomes of even 10 patients per day would quickly get out of hand. But VCF files are more compact, requiring only a few hundred megabytes per genome, which helps researchers find the specific variants they want to search in a fraction of the time. Unlike a fully sequenced genome, VCF files point only to where a persons genetic data deviates from the standardthe genome originally compiled by the Human Genome Project in 2001.

With VCF, sifting the genomes themselves for pinpoint mutations isnt the challenge for search engine companies. Most of these companies are allocating their resources toward efforts to seamlessly compile supplementary information about a specific mutation from other databases across the Web, such as the biomedical research archive PubMed or various troves of electronic medical records. Many of these tools have finely tuned algorithms that prioritize the results by credibility or relevance. You want to be able to pull together the information known about a mutation in that position [of the genome] and quickly make an assessment, says David Mittelman, the chief scientific officer for Tute Genomics, based in Provo, Utah, another company designing a genetic-search engine.

In an effort to expand the information that can be attached to a genome under examination, ViaGenetics, based in Miami Beach, Fla., is making its newly updated platform useful for researchers who want to collaborate across institutions. With ViaGenetics tools, researchers can make their data available to other users, so other people can come across these projects, request access, and form a collaboration, Gonzalez says. It helps people connect the dots between different researchers and institutions. This is especially helpful for smaller labs that may not have very extensive genome databases or for researchers from different universities working to decode the same mutation.

Although the genomic-search industry is now focused on serving scientists, that might not always be the case. Mittelman envisions that Tute Genomics could eventually serve consumers directly. People are already demanding information about their genomes just to understand themselves better, Mittelman says, but most companies dont yet consider the average person to be their primary customer. In order to make that shift, the tool will have to be even more intuitive and user-friendly. Fire-hosing someone with data thats not easy to interpret, or using terminology thats not standardized, has the potential to confuse people, he says. Privacy is also a major concern for the average user; the information that Tute users upload isnt stored permanently, Mittelman says, but users will need extra reassurance if the platform becomes available to the lay public.

And a further evolution of the industry is in the offing. Both ViaGenetics and Tute are hoping to be able to run the entire process in-housefrom the initial DNA sequencing to the presentation of final searchable results to users. The market for analyzing and interpreting genomic data is very fragmented, like the computer industry in the 1990s, where you had to go to separate providers to buy a video card or a motherboard and then try to put it together, Mittelman says. Soon this field will consolidate, as the computer industry did.

This article originally appeared in print as A Google for DNA.

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The Race to Build a Search Engine for Your DNA

Researchers explore the shift from maternal genes to the embryo's genes during development

A new study from Princeton University sheds light on the handing over of genetic control from mother to offspring early in development. Learning how organisms manage this transition could help researchers understand larger questions about how embryos regulate cell division and differentiation into new types of cells.

The study, published in the March 12 issue of the journal Cell, provides new insight into the mechanism for this genetic hand-off, which happens within hours of fertilization, when the newly fertilized egg is called a zygote.

"At the beginning, everything the embryo needs to survive is provided by mom, but eventually that stuff runs out, and the embryo needs to start making its own proteins and cellular machinery," said Princeton postdoctoral researcher in the Department of Molecular Biology and first author Shelby Blythe. "We wanted to find out what controls that transition."

Blythe conducted the study with senior author Eric Wieschaus, Princeton's Squibb Professor in Molecular Biology, Professor of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics, a Howard Hughes Medical Institute investigator, and a Nobel laureate in physiology or medicine.

Researchers have known that in most animals, a newly fertilized egg cell divides rapidly, producing exact copies of itself using gene products supplied by the mother. After a short while, this rapid cell division pauses, and when it restarts, the embryonic DNA takes control and the cells divide much more slowly, differentiating into new cell types that are needed for the body's organs and systems.

To find out what controls this maternal to zygotic transition, also called the midblastula transition (MBT), Blythe conducted experiments in the fruit fly Drosophila melanogaster, which has long served as a model for development in higher organisms including humans.

These experiments revealed that the slower cell division is a consequence of an upswing in DNA errors after the embryo's genes take over. Cell division slows down because the cell's DNA-copying machinery has to stop and wait until the damage is repaired.

Blythe found that it wasn't the overall amount of embryonic DNA that caused this increase in errors. Instead, his experiments indicated that the high error rate was due to molecules that bind to DNA to activate the reading, or "transcription," of the genes. These molecules stick to the DNA strands at thousands of sites and prevent the DNA copying machinery from working properly.

To discover this link between DNA errors and slower cell replication, Blythe used genetic techniques to create Drosophila embryos that were unable to repair DNA damage and typically died shortly after beginning to use their own genes. He then blocked the molecules that initiate the process of transcription of the zygotic genes, and found that the embryos survived, indicating that these molecules that bind to the DNA strands, called transcription factors, were triggering the DNA damage. He also discovered that a protein involved in responding to DNA damage, called Replication Protein A (RPA), appeared near the locations where DNA transcription was being initiated. "This provided evidence that the process of awakening the embryo's genome is deleterious for DNA replication," he said.

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Letting go of the (genetic) apron strings

Analysis of large epidemiologic studies identifies rare variants associated with no preventive benefit

An analysis of genetic and lifestyle data from 10 large epidemiologic studies confirmed that regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) appears to reduce the risk of colorectal cancer in most individuals. The study being published in the March 17 issue of JAMA found that a few individuals with rare genetic variants do not share this benefit. The study authors note, however, that additional questions need to be answered before preventive treatment with these medications can be recommended for anyone.

"Previous studies, including randomized trials, demonstrated that NSAIDS, particularly aspirin, protect against the development of colorectal cancer, but it remains unclear whether an individual's genetic makeup might influence that benefit," says Andrew Chan, MD, MPH, of the Massachusetts General Hospital (MGH) Gastroenterology Division, co-senior and co-corresponding author of the JAMA report. "Since these drugs are known to have serious side effects - especially gastrointestinal bleeding - determining whether certain subsets of the population might not benefit is important for our ability to tailor recommendations for individual patients."

The research team analyzed data from the Colon Cancer Family Registry and from nine studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium - which includes the Nurses' Health Study, the Health Professionals Follow-up Study and the Women's Health Initiative - comparing genetic data for 8,624 individuals who developed colorectal cancer with that of 8,553 individuals who did not, matched for factors such as age and gender. The comprehensive information on lifestyle and general health data provided by participants in the studies again confirmed that regular use of aspirin or NSAIDs was associated with a 30 percent reduction in colorectal cancer risk for most individuals. However, that preventive benefit did not apply to everyone, and the study found no risk reduction in participants with relatively uncommon variants in genes on chromosome 12 and chromosome 15.

"Determining whether an individual should adopt this preventive strategy is complicated, and currently the decision needs to balance one's personal risk for cancer against concerns about internal bleeding and other side effects," states Chan, who is an associate professor of Medicine at Harvard Medical School. "This study suggests that adding information about one's genetic profile might help in making that decision. However, it is premature to recommend genetic screening to guide clinical care, since our findings need to be validated in other populations. An equally important question that also needs to be investigated is whether there are genetic influences on the likelihood that someone might be harmed by treatment with aspirin and NSAIDs."

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The lead author of the JAMA report is Hongmei Nan, MD, PhD; formerly a research fellow at Brigham and Women's Hospital and now on the faculty at the Fairbanks School of Public Health and the Simon Cancer Center at Indiana University. Li Hsu, PhD, of the Fred Hutchinson Cancer Research Center is co-corresponding author, and Ulrike Peters, PhD, MPH, also of Fred Hutch, is co-senior author. Support for this study includes several grants from the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Genetic background determines whether aspirin/NSAIDS will reduce colorectal cancer risk

Atlanta, GA (PRWEB) March 16, 2015

African American women have higher death rates from breast cancer than do white women. Veena Rao, Ph.D., researcher, professor and co-director of the Cancer Biology Program in the department of OB/GYN at Morehouse School of Medicine, has pointed to multiple factors that contribute to the increased vulnerability of African American women, such as barriers to testing and quality of treatment. Leading medical researchers, including University of Washington geneticist and Lasker Laureate Mary-Claire King, highlight additional factors undetected inherited mutations and now recommend offering genetic testing for all women at about age 30. Dr. King will make a free, public address at the Morehouse School of Medicine on March 19, to discuss Inherited Breast Cancer: From Gene Discovery to Public Health.

Dr. Kings discovery in 1990 of the BRCA1 breast cancer gene demonstrated a mechanism of inherited cancer and proved that gene mutations could predict vulnerability to the disease.

A 2013 study of inherited predisposition to breast cancer among African American women by Dr. King and Dr. Olufunmilayo Olopade, director of The Center for Clinical Cancer Genetics, at the University of Chicago, found that 22 percent of African American breast cancer patients inherited a damaging mutation in BRCA1 or BRCA2 or another breast cancer gene. Women carrying a mutation of BRCA1 or BRCA2 have a greater than 80 percent lifetime risk of developing breast cancer, as compared with 11% for women without mutations.

Recently, Dr. King showed that women with BRCA1 or BRCA2 mutations had elevated risk for breast cancer, even if they have no family history of the disease. Therefore, she recommends that BRCA1 and BRCA2 testing be made available to all women.

I believe that every woman should be offered testing of BRCA1 and BRCA2 at about age 30 as part of routine medical care, said Dr. King. About half of women who inherit mutations in the BRCA1 or BRCA2 genes have no family history of breast or ovarian cancer and have no idea that they are carrying cancer-causing mutations. Affordable, accessible early detection is a public health priority for saving lives.

While some within the medical community voice caution that universal screening could lead to anxiety for some women, King and Olopade focus on the benefits. Having a genetic mutation doesnt mean youre definitely going to get cancer, Dr. Olopade told NPR last September. Women at greater risk should work with their doctors closely to make decisions about the best approach to reducing their chances of developing breast cancer.

Within the African American community, access to mammograms and other testing, as well as follow-up care continues to be a challenge. Disparities in availability of breast cancer care is a profound public health concern.

On March 19, Dr. King will give a special lecture, co-sponsored by the Albert and Mary Lasker Foundation and the Morehouse School of Medicine. In September 2014, the Lasker Foundation awarded Dr. King its prestigious Special Achievement Award in Medical Science for her bold, imaginative, and diverse contributions to medical science and human rights.

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Dr. Mary- Claire King to speak at Morehouse School of Medicine on how genetic screening for all women can lower risk ...

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Newswise WASHINGTON Today AACC sent formal comments to the Food and Drug Administration (FDA) on the agencys proposed regulation of next-generation sequencing tests. AACC appreciates FDAs efforts to seek input from the healthcare community before developing new policy in this area, but is concerned that FDA regulation of next-generation sequencing could impede the advancement of precision medicine.

Precision medicine uses a persons unique biological makeup, including genetics, to determine which treatments that person would respond to best. Genetic tests hold the potential to predict an individuals risk of developing numerous different conditions throughout life. Having this knowledge could lead one to take a more proactive approach to his or her health, particularly with respect to chronic diseases such as cardiovascular disease and diabetes that could be prevented with basic lifestyle changes. Next-generation sequencing will enhance the application of precision medicine by making genetic testing more readily available.

After reviewing FDAs preliminary discussion paper on the topic, Optimizing FDAs Regulatory Oversight of Next-Generation Sequencing Diagnostic Tests, AACC recommends that oversight of next-generation sequencing remain under the Clinical Laboratory Improvement Amendments (CLIA) like other laboratory developed tests. CLIA-regulated laboratories conducting next-generation sequencing testing are experienced in developing, verifying, and performing clinical tests. AACC believes that CLIA-recognized accrediting bodies and professional societies should continue to take the lead in providing oversight and guidance for next-generation sequencing testing in the absence of specific, identified problems with this approach.

AACC agrees with the FDA that next-generation sequencing tests offer great opportunities for advancing laboratory medicine and improving patient care, and we commend the agencys efforts to initiate a dialogue among the various organizations and professionals involved in next-generation sequencing and those affected by such testing, said AACC President Dr. David D. Koch. We believe, however, that the current oversight mechanisms in place for next-generation sequencing are sufficient for dealing with the particular challenges this technology presents and that further FDA involvement at this time might hinder the advancement of this field.

Read AACCs comment letter here.

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About AACC Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of breaking laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit http://www.aacc.org.

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AACC Cautions FDA Against Over-Regulating the Genetic Testing Technology Vital to Precision Medicine