Category Archives: Genetics

In September, the world of entertainment news buzzed with word that Kim Kardashian West tested positive for lupus and rheumatoid arthritis. The star underwent further tests, however, resulting in a diagnosis of psoriatic arthritis instead. While all three autoimmune disorders share some signs and symptoms, psoriatic arthritis is generally considered to have a better prognosis than lupus. That said, the conditions can co-exist and lupus has gotten a reputation for being difficult to diagnose, especially in the absence of the butterfly-shaped rash on ones cheeks and nose.

Im so relieved. The pain is going to come and go sometimes, but I can manage it and this is not going to stop me, Kardashian said in an article in response to receiving her psoriatic arthritis diagnosis. Her relief at not having lupus is understandable, given that lupus can affect a greater number of organs and systems in the body and is considered to be life-threatening.

Lupus, rheumatoid arthritis and psoriatic arthritis are examples of some conditions that are often considered when an individual is undergoing diagnosis for certain autoimmune diseases, because they share several symptoms and can trigger positive results in the same diagnostic tests. Kim Kardashian received the initial news that she had lupus or rheumatoid arthritis likely due to positive antinuclear antibody (ANA) test results.

An ANA is a blood test ordered when a doctor, usually a rheumatologist, suspects that a patient has a particular kind of autoimmune disorder. This test checks for the existence of autoantibodies, which are produced when a persons body is, in effect, attacking itself and several areas of the body are affected. A positive ANA test usually indicates that the doctors suspicions are confirmed, and then other factors (like medical and family history) need to be considered and more tests done to arrive at a diagnosis.

Psoriatic arthritis is usually diagnosed between the ages of 20 and 50, and occurs in women and men equally. While there is no cure, appropriate and early treatment can help prevent major damage to affected parts of the body.

Psoriatic arthritis appears in a minority of individuals who have already been diagnosed with psoriasis, an autoimmune skin condition with which Kim Kardashian and her mother, Kris Jenner, had already been diagnosed. Psoriatic arthritis affects around 520,000 individuals in the United States alone.

The autoimmune condition is believed to be caused by a combination of genetic factors and environmental triggers. So while some people inherit psoriatic arthritis-related genes, only a subset of those individuals will go on to develop the condition. In these cases, the disease could be triggered by other illnesses or infections, various forms of extreme stress, poor diet, smoking, and so on.

Around 40 percent of psoriatic arthritis patients have one or more close family members with psoriasis or psoriatic arthritis diagnosis, which strongly indicates that the disease is hereditary. Interestingly, recent research has suggested that psoriasis patients who go on to develop psoriatic arthritis have a different genetic profile than those who do not. And the most well-studied of the psoriatic arthritis genes belong to a family of genes called the human leukocyte antigen (HLA) complex, which help the body tell the difference between its own proteins and viral or bacterial proteins.

According to Genetics Home Reference by the U.S. National Library of Medicine, Variations of several HLA genes seem to affect the risk of developing psoriatic arthritis, as well as the type, severity, and progression of the condition.

Ive been feeling so tired, so nauseous, and my hands are really getting swollen. I feel like I literally am falling apart. My hands are numb, Kardashian said on a recent episode of Keeping Up with the Kardashians.

These kinds of descriptions are common in all three conditions lupus, rheumatoid arthritis, and psoriatic arthritis though each patient presents with a different array of symptoms, and all with varying degrees of severity. The main symptoms of psoriatic arthritis are pain, stiffness, and swelling in affected joints, along with chronic fatigue. Joints near the end of the fingertips and tips of the toes are often affected, as are bones in the spine.

The symptoms of psoriatic arthritis tend to worsen over time, though some patients experience periods of remission when symptoms temporarily improve. Compared to rheumatoid arthritis, psoriatic arthritis is more likely to cause swelling in the smallest joints of the fingers and toes, foot pain (in the heel and/or sole of the foot), and lower back pain caused by inflammation in vertebral joints. Patients with psoriatic arthritis are also more likely to experience symptoms on one side of the body or in different appendages on each side (in other words, it tends to be an asymmetric disease), whereas patients with rheumatoid arthritis are more likely to experience symptoms that affect both sides of the body equally (symmetric disease).

Most if not all patients with psoriatic arthritis also have psoriasis, an autoimmune condition that causes red, scaly patches of skin that can be itchy, painful and embarrassing. Psoriasis usually precedes the onset of psoriatic arthritis by several years. People with psoriatic arthritis commonly experience fingernail changes, too, such as the formation of a pitted or ridged nail surface, or the nails become separated from the nail beds.

There are several treatment options for psoriatic arthritis, which include nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and pain, immunosuppressants to suppress the immune system, disease-modifying antirheumatic drugs (DMARDs) to slow the progression of the disease, and newer medications that minimize the activity of certain enzymes involved in the inflammatory process. Treatment plans may also involve steroid injections administered directly into affected joints, or joint replacement surgery in cases where the disease has significantly progressed.

Kristen Hovet covers genetics, medical innovations and the intersection of sociology and culture. The North Dakota native is based in Vancouver, Canada, where she is working on a masters degree in health communication at Washington State University. Follow her on her website or Twitter @kristenhovet

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Kim Kardashian West's battle with psoriatic arthritis: Will understanding the genetics of the autoimmune disorder point to a cure? - Genetic Literacy...

IRVING, Texas and ALISO VIEJO, Calif., Dec. 4, 2019 /PRNewswire/ --Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, and Ambry Genetics(Ambry), a leading clinical genetic testing company, today announced that Caris will begin offering Ambry's 67-gene CancerNext-Expanded panel to evaluate the hereditary risks for cancer. Combined with Caris' somatic (tumor) tests that analyze a cancer's detailed molecular makeup, Caris will provide patients and their healthcare providers unparalleled information to more accurately diagnose and treat cancer. This will be the most comprehensive, clinically relevant molecular and genetic offering on the market today to guide treatment and management of cancer.

"We are committed to providing clinicians with high-quality information they can use to inform treatment decisions," said David D. Halbert, Caris Life Sciences Chairman, Chief Executive Officer and Founder. "By partnering with Ambry Genetics to better inform patient care, we are able to provide clinicians a greater ability to learn about a cancer's molecular composition."

Caris currently offers clinicians Caris Molecular Intelligence, a proprietary, comprehensive tumor profiling approach that assesses DNA, RNA, and proteins unique to an individual's cancer to reveal a molecular blueprint in order to guide more precise and individualized treatment decisions.

Through the partnership, Caris will now offer Ambry's CancerNext-Expanded hereditary cancer panel. This panel analyzes 67 genes associated with an increased hereditary risk of cancer, including brain, breast, colon, ovarian, pancreatic, prostate, renal, uterine, and many other cancers. Its comprehensive testing identifies inherited risks for cancer in order for clinicians to accurately diagnose, treat, and manage cancer risks for each patient's needs.

"To best diagnose and treat cancer, clinicians must understand whether patients have mutations in genes associated with an increased risk for hereditary cancer," said Aaron Elliott, Chief Executive Officer of Ambry. "Caris' molecular tests combined with Ambry's germline genetic testing, give clinicians the most comprehensive, clinically relevant molecular profile on the market to guide treatment and management."

The combined Caris and Ambry testing is now available nationwide.

"Being able to simultaneously conduct comprehensive tumor genomic testing and multi-gene germline sequencing is invaluable, especially for sick patients at the beginning of their cancer journey," said Michael J. Hall, M.D., M.S., Chair, Department of Clinical Genetics at Fox Chase Cancer Center. "This is information I can immediately begin using for my patients to more accurately diagnose them and to better individualize their treatments."

About Caris Life Sciences Caris Life Sciences is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation. The company's suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps physicians and cancer patients make more precise and personalized treatment decisions.

Caris is also advancing precision medicine with Next Generation Profiling that combines its innovative service offerings, Caris Molecular Intelligence and ADAPT Biotargeting System, with its proprietary artificial intelligence analytics engine, DEAN, to analyze the whole exome, whole transcriptome and complete cancer proteome. This information, coupled with mature clinical outcomes on thousands of patients, provides unmatched molecular solutions for patients, physicians, payers and biopharmaceutical organizations.

Whole transcriptome sequencing with MI Transcriptome provides the most comprehensive and unique RNA analysis available on the market and covers all 22,000 genes, with an average of 60 million reads per patient, to deliver extremely broad coverage and high resolution into the dynamic nature of the transcriptome. Assessing the whole transcriptome allows us to dig deeper into the RNA universe to uncover and detect fusions, splice variants, and expression changes that provide oncologists with more insight and actionable information when determining treatment plans for patients.

Caris Pharmatech, a pioneer of the original Just-In-Time research system with the largest research-ready oncology network, is changing the paradigm from the traditional physician outreach model to a real-time approach where patient identification is completed at the lab and the physician is informed so that the patient can be enrolled days earlier, and remain in the local physician's care, without having to travel to a large central trial site. This fundamentally redefines how pharmaceutical and biotechnology companies identify and rapidly enroll patients in precision oncology trials by combining Caris' highest quality industry leading large-scale molecular profiling services with Pharmatech's on-demand site activation and patient enrollment system.

Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets. To learn more, please visitwww.CarisLifeSciences.comor follow us on Twitter (@CarisLS).

About Ambry GeneticsAmbry Genetics, as part of Konica Minolta Precision Medicine, excels at translating scientific research into clinically actionable test results based upon a deep understanding of the human genome and the biology behind genetic disease. Our unparalleled track record of discoveries over 20 years, and growing database that continues to expand in collaboration with academic, corporate and pharmaceutical partners, means we are first to market with innovative products and comprehensive analysis that enable clinicians to confidently inform patient health decisions. We care about what happens to real people, their families, and the people they love, and remain dedicated to providing them and their clinicians with deeper knowledge and fresh insights, so together they can make informed, potentially life-altering healthcare decisions. For more information, please visitambrygen.com.

Caris Company Contact & Media:Srikant RamaswamiVice President, Chief Communications Officersramaswami@carisls.com +1-214-769-5510

Ambry Genetics Media Contact:Liz Squirepress@ambrygen.com (202) 617-4662

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Caris Life Sciences and Ambry Genetics Partner to Advance Cancer Care - PRNewswire

In the 1950s, Dmitri K. Belyaev began one of the most famous experiments in animal domestication. Dr. Belyaev, a geneticist at the Institute of Cytology and Genetics in Novosibirsk, Russia, selectively bred foxes that he had acquired from a fur farm, concentrating only on reducing their fear of humans.

Within 10 generations, he wrote in 1979, Like dogs, these foxes seek contact with familiar persons, tend to get close to them, and lick their hands and faces.

In a new paper in the journal Trends in Ecology and Evolution, several scientists have challenged a common interpretation of Dr. Belyaevs results, and have questioned whether scientists who study domestication have any common understanding of what the word means.

The authors dont dispute the essence of Dr. Belyaevs work: the selection for tameness, which is regarded as profoundly important in exploring the genetics and evolution of behavior.

But that wasnt all that Dr. Belyaev discovered. His foxes also showed physical changes, like piebald coats and floppy ears characteristics shared by dogs, cows and other domesticated animals.

Dr. Belyaev and the researchers who followed up his work suggested, as had Charles Darwin before them, that there might be a collection of physical traits that go along with tameness called domestication syndrome.

The authors of the new paper argue that this idea is undermined by an intriguing sub-chapter in the long history of the fur trade in Canada. The reaction to that criticism from other scientists has been mixed, reflecting contentious but cordial disagreements about what domestication is and how it happens.

The average pet lover may know the story of the foxes from a book by Lee Alan Dugatkin and Lyudmila Trut, who collaborated with Dr. Belyaev, called How to Tame a Fox (and Build a Dog).

Far fewer people probably know about the development of fox farming on Prince Edward Island, Canadas smallest province. This history is buried in plain sight, you might say, since you can learn about it easily if you visit International Fox Museum and Hall of Fame on the island.

The museum is not a common destination for evolutionary biologists who specialize in domestication. But one of them did visit back in 2015, and he was taken aback.

The late Raymond Coppinger, a biologist at Hampshire College in Massachusetts who was a major contributor to the study of dog evolution, toured the museum and returned full of questions.

He saw these pictures of spotted foxes, and they looked just like the Belyaev foxes, recalled Kathryn Lord, an animal behaviorist at the Broad Institute in Cambridge, Mass., and the first author of the new paper. Dr. Coppinger was her mentor at Hampshire College.

There have been academic reports as well, suggesting that the Russian foxes hailed from Prince Edward Island, Dr. Lord said: Different pieces of the story were all over, but nobody had put it together.

As it turned out, genetic tests showed that Dr. Belyaevs foxes did have roots in eastern Canada, which almost certainly meant Prince Edward Island. So the question bothering Dr. Coppinger and Dr. Lord was this: How much domestication had gone on before the famous fox experiment began?

She got the attention of Elinor Karlsson, a geneticist at the Broad Institute in whose lab Dr. Lord worked. And she drew in Greger Larson, a specialist in ancient canine DNA at the University of Oxford in England, who is deeply involved in questions of dog evolution and domestication. They began to refine the work Dr. Lord and Dr. Coppinger had already done.

Dr. Belyaev had plainly stated that his foxes were from farmed stock. So some domestication must have occurred before his experiment, said Anna Kukekova, a geneticist at the University of Illinois who researches the genetics of Russian foxes and has collaborated with Dr. Trut.

Dr. Belyaev recognized that fur farmers would have chosen animals that were at least somewhat tolerant of people, Dr. Kukekova said. But Dr. Belyaev also described his foxes as mostly uncomfortable with people, virtually wild animals. Now, Dr. Lord and her colleagues suggest otherwise.

Fox-farming pioneers on Prince Edward Island began by breeding wild-caught black foxes, also called silver foxes, a color variant of the red fox (Vulpes vulpes) common all over the world.

They were bred mainly for the look of the pelts. In 1910, one company sold 25 skins for $34,649.50, according to Silver Fox Odyssey: History of the Canadian Silver Fox Industry.

Then breeding stock became more profitable. Old proven breeders of good quality were valued during the last months of 1912 at from $18,000 to $25,000 a pair, according to a 1913 report by the Canadian government quoted in Silver Fox Odyssey. Eventually the industry declined, and there are only traces of it remaining.

The museum on Prince Edward Island has old photographs that show foxes looking very comfortable with human beings. And as Dr. Lord took a deep dive into fox-farming history, she found other sources suggesting the animals were already somewhat domesticated, including The Black Fox Magazine, a publication for people who hoped to make their fortune raising foxes for their pelts.

The magazine offers a glimpse into a bygone world. For example, an article by F. E. Muzzy in the January 1921 issue described the 1921 International Fox Show in Montreal. Mr. Muzzy wrote that one of the islands fox industry bigwigs, Leo Frank, brought a pair of tame foxes to town, and not only walked them on leashes but took them to a dance where the girls did the fox trot with these foxes around their necks.

Hearsay, of course, but a good story, given the other evidence.

Dr. Belyaevs claims in his landmark article were twofold. One, he had shown how quickly one could select for tameness and tolerance of human beings. The second was that breeding, or selecting for lack of fear in the presence of humans, also had brought about other changes, like floppy ears, spotted coats and differences in tail carriage.

He didnt use the term, but that suite of physical traits came to be known as domestication syndrome. And it was thought to cross species, showing up in cows and goats, for example, as well as foxes.

The idea of domestication syndrome, said Dr. Larson, has been appealing but not thoroughly examined. He, Dr. Lord and their colleagues looked at 10 papers that defined domestication syndrome and found that there wasnt one trait that was included in all the definitions. What the hell are we even talking about here? he asked.

The authors argue that the foxes already showed some of the physical traits that Dr. Belyaev described by the time he got them. His breeding may, however have affected how frequently the traits appeared.

The researchers also note that different species show different combinations of the traits that were proposed to be in the syndrome.

The paper provides the final nail in the coffin to the idea of a universal set of traits characterizing all domesticated animals, said Marcelo R. Snchez-Villagra, a professor of paleobiology at the University of Zurich who studies domestication and was not involved in the study.

But that was not surprising, he added, given other research showing varying processes of domestication. He appreciated the critical look at the fox experiment, because I also think its value has been overestimated.

Dr. Kukekova said she found that critique oversimplified, although she sympathized: I completely understand their frustration with domestication syndrome.

But many aspects of the fox domestication experiment were not presented correctly, she added.

Dr. Belyaev created a pattern of behavior totally different from that of the farmed foxes he began with, Dr. Kukekova said. The old photographs of the friendly foxes were not scientific evidence, she added, and there was no evidence that the foxes actively sought out human interaction, as Dr. Belyaevs did.

She cautioned, however, that there is an enormous difference between a domesticated animal and a pet. The foxes are domesticated, but they are not pets, she said.

Adam Wilkins, a biologist at Humboldt University in Berlin, found the new paper deeply flawed. In a personal letter to the authors, he argued that mammals do share a suite of physical characteristics that go along with tameness.

Dr. Wilkins has argued that mutations in cells in a part of the embryo called the neural crest are linked to behavioral and physical changes.

The fact that different kinds of domesticated animals have somewhat different sets of the affected traits is perfectly consistent with the idea of a syndrome, he wrote in an email.

Asked if there was a working definition of domestication, Dr. Sanchez-Villagra replied, There are as many as there are authors who have provided a definition.

Despite their differences, the spirit of collaboration and scientific discourse among researchers in the quite small field of canine evolution might best be captured by Dr. Wilkins at the end of his letter.

He tempered his criticisms with a friendly note, concluding, We clearly share a strong interest in the subject and I suspect a love of dogs. Here, I attach a picture of my personal favorite domesticated animal, my dog Wolfie.

Originally posted here:
Why Are These Foxes Tame? Maybe They Werent So Wild to Begin With - The New York Times

SALT LAKE CITY, Dec. 03, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, today announced that multiple studies will be presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) being held Dec. 10-14, 2019 in San Antonio, Tx.

"We are excited to present new data from several studies at SABCS this year, said Nicole Lambert, president of Myriad Oncology. "Our data represents Myriads commitment to advancing precision oncology for people with breast cancer and improving outcomes.

A list of the companys presentations at SABCS is below. Please visit Myriad at booth #113 to learn more about our portfolio of genetic tests for breast cancer. Follow Myriad on Twitter via @myriadgenetics and keep up to date with Symposium news by using the hashtag #SABCS19.

About Myriad myRisk Hereditary CancerThe Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

About riskScoreriskScore is a new clinically validated personalized medicine tool that enhances Myriads myRisk Hereditary Cancer test. riskScore helps to further predict a womens lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from greater than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About EndoPredictEndoPredict is a second-generation, prognostic test that aids personalized treatment planning for patients with early-stage breast cancer. EndoPredict has been validated in over 3500 patients with node-negative and node-positive disease and is the leading breast prognostic in Europe. In contrast to first-generation multigene prognostic tests, EndoPredict incorporates a 12-gene molecular score with known prognostic factors tumor size and nodal status. In clinical studies, EndoPredict demonstrated its robust ability to predict recurrence risk across multiple time-periods: 0-5, 5-10, and 5-15 years. EndoPredict provides clinically actionable information to physicians and patients as they consider the use of adjuvant chemotherapy and extended endocrine therapy.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice HRD, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Companys data across multiple genetic tests being featured at the 2019 San Antonio Breast Cancer Symposium being held Dec. 10-14, 2019 in San Antonio, Tx.; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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Myriad Genetics to Present Multiple Studies on Breast Cancer at the 2019 San Antonio Breast Cancer Symposium - BioSpace

Evolution is generally thought of as a linear process: Species split off from one another over time, move to different places, and adapt different traits. But species like those in the Heliconius genus make patterns of evolution more interesting.

We need to take into account in our evolutionary models that we can get gene flow between species, Edelman says.

Heliconius made sense to study because of its hybrid-making tendencies. Its also just a cool really insect. The adult Heliconius eats pollen, which no other butterfly does. And Heliconius is smart, Edelman says. It has a home range, meaning it will go to visit the same flower every day, a habit more commonly associated with mammals.

The findings have potential implications for conservation and preserving pollinator populations. Studies show that species variation is key to protecting those populations in a changing climate.

One good thing about genetic diversity is if you have a really variable and diverse population, when environmental conditions change, you have a better chance of responding to them, Edelman says.

So how does hybridization factor in? Researchers dont all agree on whether its likely to contribute to genetic diversity. But it very well might.

Its at least somewhat likely that youre going to increase your variation rather than decrease it, Edelman says.

Conservation can involve protecting species by keeping out its close relatives, to avoid hybridization or a species takeover, but for species like these butterflies, that strategy may not work as well.

Hybridization is pretty common in nature, Edelman says. In some cases it might be good to bring in other species and increase genetic diversity for conservation purposes.

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Weird butterfly genetics counter popular theory of evolution - Inverse

New genetic research has identified fin whales in the northern Pacific Ocean as a separate subspecies, reflecting a revolution in marine mammal taxonomy as scientists unravel the genetics of enormous animals otherwise too large to fit into laboratories.

"The increasing study of cetacean genetics is revealing new diversity among the world's whales and dolphins that has not been previously recognized," said Eric Archer, a geneticist at NOAA Fisheries' Southwest Fisheries Science Center (SWFSC) in La Jolla, California. Archer is the lead author of the identification of the new subspecies of fin whale.

"There's definitely more diversity out there than has been on the books," he said. "There has been a wave of progress in cetacean taxonomy."

Fin whales are the second-largest whale on earth and the fastest whales in the ocean, which made them one of the last whale species hunted to the edge of extinction. Whalers killed about 46,000 fin whales in the North Pacific Ocean from 1947 to 1987. They are also one of the least known large whale species. They mainly roam the open ocean, farther from coastlines where they might be seen and studied more easily. They have been observed off the south Washington coast.

Scientists from NOAA Fisheries, Ocean Associates Inc., Cascadia Research Collective, Tethys Research Institute, and Universidad Autnoma de Baja California Sur, identified the new subspecies. Their findings were published in an article in the Journal of Mammalogy, naming it Balaenoptera physalus velifera, which means "carrying a sail" in Latin.

"We don't get a lot of (genetic) material from them," Archer said. However, advancing technologies allowed Archer and his colleagues to extract the detail they needed from samples at the SWFSC. The center's Marine Mammal and Turtle Molecular Research Sample Collection is one of the largest collections of marine mammal genetic material in the world. They obtained additional samples from museums and other collections.

Traditional taxonomy the division of biological variation into recognized species and subspecies involves comparing telltale parts of the skeleton such as the skull. For whales, this may weigh hundreds of pounds. Few institutions can amass a large enough collection to compare different individuals from around the world.

"Fin whales measure 60 to 70 feet long and their skulls are around 15 feet long," Archer said. "Just housing a couple takes a lot of room."

Increasingly powerful genetic technologies now allow scientists to compare genes instead of skeletons. They extract DNA from tissue samples the size of a pencil eraser obtained from whales in the field.

"It's the only realistic way to do this, because you cannot get enough examples to determine the difference through morphology alone," Archer said. As they have looked more closely at the genetic patterns of whales around the world, scientists have discovered much more complex differences between them.

"Instead of digging through museum storage facilities for skulls to describe species or subspecies, genetic data unlock our ability to describe unique populations of whales across the globe," said research biologist Barbara Taylor, leader of the SWFSC's Marine Mammal Genetics Program. "It is a new way of looking at these animals."

Comparing the DNA from fin whales in the Pacific and the Atlantic oceans showed the scientists that they have been separated for hundreds of thousands of years. They also could assign individual fin whale samples to their ocean of origin using the genetic data. This is further evidence that they are separate and distinct subspecies.

Genetic research by NOAA Fisheries scientists has also revealed new details of other whales, including a new species of Baird's beaked whale. It may also help determine whether a recently documented type of killer whale off South America represents a new species.

Similar genetic details can also help tailor protections for threatened or endangered whales, because the Endangered Species Act recognizes separate subspecies. That means that managers can target ESA safeguards for those subspecies that need it even when others may have recovered. This could make conservation efforts more efficient and effective.

About 14,000 to 18,000 fin whales in the northern Pacific Ocean will be affected by the new subspecies designation. NOAA Fisheries has documented that their numbers are increasing.

"There are other new species and subspecies that we are learning about thanks to the technology that has made this possible," Archer said. "It is changing the field."

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Genetics reveal Pacific subspecies of fin whale | South County News - Chinook Observer

DUBLIN--(BUSINESS WIRE)--The "The Global Genetic Testing Market by Hereditary, Newborn, NIPT, Oncology, Pharmacogenomic and Direct to Consumer, With Executive and Consultant Guides 2020 to 2024" report has been added to ResearchAndMarkets.com's offering.

This report forecasts the market size out to 2024. The report includes detailed breakouts for 14 countries and 5 regions.

Will all newborns receive Whole Genomic Sequencing at birth? What key interest is driving 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.

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 opportunities and pitfalls. Understand growth expectations and the ultimate market forecasts for the next five years.

All report data is available in Excel format on request

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

1.3.1 Revenue Market Size

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

1.4.1 U.S. Medicare Expenditures for Laboratory Testing

2. Market Overview

2.1 Market Participants Play Different Roles

2.1.1 Supplier/pharmaceutical

2.1.2 Independent lab specialized/esoteric

2.1.3 Independent lab national/regional

2.1.4 Independent lab analytical

2.1.5 Public National/regional lab

2.1.6 Hospital lab

2.1.7 Physician lab

2.1.8 DTC Lab

2.1.9 Independent Genetic Testing Lab

2.1.10 Audit Body

2.2 Genetic Tests -Types, Examples and Discussion

2.2.1 Preimplantation Genetic Diagnosis- An Emerging Market

2.2.2 Prenatal Diagnosis - New Technologies Create Opportunity

2.2.3 Newborn Screening

2.2.2 Diagnostic Testing

2.2.3 Carrier Testing

2.2.6 Predictive and Presymptomatic Testing

2.2.7 Pharmacogenomics

2.2.8 Forensic Testing

2.2.9 Parental Testing

2.2.10 Ancestral Testing

2.3 Industry Structure

2.3.1 Hospital's Testing Share

2.3.2 Economies of Scale

2.3.2.1 Hospital vs. Central Lab

2.3.3 Physician Office Lab's

2.3.4 Physician's and POCT

2.4 Market Shares of Key Genetics Players - Analysis

3. Market Trends

3.1 Factors Driving Growth

3.1.1 Genetic Discoveries Creating New Diagnostic Markets

3.1.2 Aging Population a Boon for Diagnostics

3.1.3 Pharmacogenomics Drives Further Growth

3.1.4 Oncology and Liquid Biopsy Enter New Era

3.1.5 Fertility Practice Growth drives market

3.1.6 Direct to Consumer begins to break out

3.2 Factors Limiting Growth

3.2.1 Increased Competition Lowers Price

3.2.2 Lower Costs

3.2.3 Testing usage analysis curtailing growth

3.2.4 Wellness has a downside

3.3 Instrumentation and Automation

3.3.1 Instruments Key to Market Share

3.3.2 Bioinformatics Plays a Role

3.4 Diagnostic Technology Development

3.4.1 Next Generation Sequencing Fuels a Revolution

3.4.2 Impact of NGS on pricing

3.4.3 POCT/Self Testing Disruptive Force

3.4.4 Pharmacogenomics Blurs Diagnosis and Treatment

3.4.5 CGES Testing, A Brave New World

3.4.6 Biochips/Giant magnetoresistance based assay

4. Genetic Testing Recent Developments

4.1.1 Importance of This Section

4.1.2 How to Use This Section

5. Profiles of Key Companies

6. Global Market Size

6.1 Global Market by Country

6.2 Global Market by Application

7. Market Sizes by Application

7.1 Hereditary Testing Market

7.2 Newborn Testing Market

7.3 NIPT Testing Market

7.4 Oncology Testing Market

7.5 Pharmacogenomic Testing Market

7.6 Direct to Consumer Testing Market

8. The Future of Genetic Testing

For more information about this report visit https://www.researchandmarkets.com/r/2llelf

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Global Genetic Testing Markets 2020-2024 | by Hereditary, Newborn, NIPT, Oncology, Pharmacogenomic & Direct to Consumer - ResearchAndMarkets.com -...

This is concerning, the study's lead researcher Dr Ruth Leibowitz said, because GPs are the first point of call for most pregnant women and those seeking preconception medical care.

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"One theory is that GPs simply dont really know about the tests and the majority of these tests are being driven by patients requesting it," Dr Leibowitz said during a presentation of her findings at the GP19 conference in Adelaide last Friday.

When prenatal testing shows a fetus is at risk, families are faced with a profound and difficult decision on whether to keep the baby or terminate the pregnancy.

Many couples who are found to be carriers of the mutations prior to pregnancy can use IVF in conjunction with genetic testing of embryos to avoid having a child with a genetic condition.

Of the 21,172 women screened, one in 20 were carriers for at least one of the severe genetic disorders.

About 70 per cent were in the highest socio-economic quartile as measured by residential postcode. About 53 per cent were pregnant at the time of screening.

Earlier this year, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists set new guidelines, recommending that all women planning a pregnancy or in their first trimester should be given information about preconception carrier screening.

But Professor Martin Delatycki, clinical director of the Victorian Clinical Genetics Services and member of the Genomics Advisory Working Group, estimates less than 10 per cent of aspiring parents are offered such screening.

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"What the results show us is that GPs are in an ideal position to offer it because they see women before they are pregnant," Professor Delatycki said.

"When women are not pregnant and they have screening, they have much more time to make a decision if theyre at high risk of having a child with one of the genetic conditions.

"It is very critical its a choice for people, not just a routine test," he said. "Because its not right for everybody.

Royal Australian College of General Practitioners president Harry Nespolon argued the onus should be on obstetricians with the expertise to discuss genetic testing with would-be parents, with many GPs choosing to refer women on to genetic counsellors.

For some patients, testing for the rare conditions went against their belief system, Dr Nespolon said.

"This is not a decision to be taken lightly because there is a lot to consider about requesting genetic screening, ultimately it can affect patients pyschologically and financially. It can affect people quite deeply and the choices they make."

Carrier screening to determine if couples carry the mutations for SMA, cystic fibrosis and fragile X is not routinely offered and many doctors do not know the tests exist.

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Professor Delatycki said recent research pointed to women having a higher chance of having a baby with one of the three genetic conditions, than there is of having a baby with Down Syndrome.

The tests can cost up to $1800 for couples and are not covered by Medicare, prompting concerns that only wealthy aspiring parents can take this precaution in a bid to avoid having a baby with a severe genetic condition.

Fragile X syndrome causes intellectual disability and behavioural and learning challenges, and is also the most common single-gene cause of autism worldwide. Spinal muscular atrophy is a severe muscle-wasting disease, while cystic fibrosis damages the lungs and digestive system.

The landmark Mackenzie's Mission trial has begun recruiting 10,000 Australian couples to be screened for 500 severe and deadly genetic conditions.

The results of the trial are expected to inform whether the federal government will introduce Medicare subsidies for carrier screening.

Melissa Cunningham is The Age's health reporter.

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GPs urged to inform women about pre-pregnancy genetic testing - The Age

SALT LAKE CITY, Nov. 01, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc., (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, today announced that three studies on Vectra will be featured at the 2019 American College of Rheumatology (ACR) Annual Meeting being held Nov. 8-13, 2019 in Atlanta, GA.

"We are excited to share important new data that demonstrates how precision medicine can advance care for people with rheumatoid arthritis (RA)," said Elena Hitraya, M.D., Ph.D., rheumatologist and chief medical officer at Myriad Autoimmune. "Our studies show that Vectra, an objective measure of RA inflammation, helps identify people with RA that are at risk of joint damage and cardiovascular risk.

A list of presentations at 2019 ACR is below. Please visit Myriad Autoimmune at booth #1419 to learn more about Vectra. Follow Myriad on Twitter via @myriadgenetics and follow meeting news by using the hashtag #ACR19.

Abstract

Author

Poster Details

Vectra

Predicting Risk of Radiographic Progression for Patients with Rheumatoid Arthritis

Jeffrey Curtis

Joshua Baker

Jeffrey Curtis

About VectraVectra is a multi-biomarker molecular blood test that provides an objective and personalized measure of inflammatory disease activity in patients with rheumatoid arthritis. Vectra provides unsurpassed ability to predict radiographic progression and can help guide medical management decisions with the goal of improving patient outcomes. Vectra testing is performed at a state-of-the-art CLIA (Clinical Laboratory Improvement Amendments) facility. Test results are reported to the physician five to seven days from shipping of the specimen. Physicians can receive test results by fax or the private web portal, VectraView. For more information on Vectra, please visit: http://www.vectrascore.com.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice HRD, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to data being presented for its genetic tests at the American College of Rheumatology Annual Meeting being held Nov. 8-13, 2019 in Atlanta, GA; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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Myriad Genetics Announces Multiple Presentations at the 2019 American College of Rheumatology Annual Meeting - BioSpace

By Mitch LeslieOct. 17, 2019 , 2:00 PM

Mice put human runners to shame. Despite taking puny strides, the rodents can log 10 kilometers or more per night on an exercise wheel. But the mice that muscle biologist Eric Olson of the University of Texas Southwestern Medical Center in Dallas and colleagues unveiled in 2015 stood out. On a treadmill, the mice could scurry up a steep 10% grade for about 90 minutes before faltering, 31% longer than other rodents. Those iron mice differed from counterparts in just one small waythe researchers had genetically altered the animals to lack one muscle protein. That was enough to unleash superior muscle performance. "It's like you've taken the brakes off," Olson says.

Just as startling was the nature of the crucial protein. Muscles house some gargantuan proteins. Dystrophin, a structural protein whose gene can carry mutations that cause muscular dystrophy, has more than 3600 amino acids. Titin, which acts like a spring to give muscles elasticity, is the biggest known protein, with more than 34,000 amino acids. The protein disabled in the mice has a paltry 46. Although researchers have probed how muscles work for more than 150 years, they had completely missed the huge impact this tiny protein, called myoregulin, has on muscle function.

Olson and his colleagues weren't the only ones to be blindsided by Lilliputian proteins. As scientists now realize, their initial rules for analyzing genomes discriminated against identifying those pint-size molecules. Now, broader criteria and better detection methods are uncovering minuscule proteins by the thousands, not just in mice, but in many other species, including humans. "For the first time, we are about to explore this universe of new proteins," says biochemist Jonathan Weissman of the University of California, San Francisco.

Biologists are just beginning to delve into the functions of those molecules, called microproteins, micropeptides, or miniproteins. But their small size seems to allow them to jam the intricate workings of larger proteins, inhibiting some cellular processes while unleashing others. Early findings suggest microproteins bolster the immune system, control destruction of faulty RNA molecules, protect bacteria from heat and cold, dictate when plants flower, and provide the toxic punch for many types of venom. "There's probably going to be small [proteins] involved in all biological processes. We just haven't looked for them before," says biochemist Alan Saghatelian of the Salk Institute for Biological Studies in San Diego, California.

The venom of this predatory water bug has more than a dozen small proteins.

Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNAand RNAthat were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are," says microbiologist and molecular biologist Gisela Storz of the National Institute of Child Health and Human Development in Bethesda, Maryland.

Despite the remaining mysteries, scientists are already testing potential uses for the molecules. One company sells insecticides derived from small proteins in the poison of an Australian funnel-web spider. And a clinical trial is evaluating an imaging agent based on another minute protein in scorpion venom, designed to highlight the borders of tumors so that surgeons can remove them more precisely. Many drug companies are now searching for small proteins with medical potential, says biochemist Glenn King of the University of Queensland in St. Lucia, Australia. "It's one of the most rapidly growing areas."

Other short amino acidchains, often called peptides or polypeptides, abound in cells, but they are pared-down remnants of bigger predecessors. Myoregulin and its diminutive brethren, in contrast, are born small. How tiny they can be remains unclear. Fruit flies rely on a microprotein with 11 amino acids to grow normal legs, and some microbes may crank out proteins less than 10 amino acids long, notes microbial genomicist Ami Bhatt of Stanford University in Palo Alto, California. But even the largest small proteins don't measure up to average-size proteins such as alpha amylase, a 496amino-acid enzyme in our saliva that breaks down starch.

Few small proteins came to light until recently because of a criterion for identifying genes set about 20 years ago. When scientists analyze an organism's genome, they often scan for open reading frames (ORFs), which are DNA sequences demarcated by signals that tell the cell's ribosomes, its proteinmaking assembly lines, where to start and stop. In part to avoid a data deluge, past researchers typically excluded any ORF that would yield a protein smaller than 100 amino acids in eukaryotes or 50 amino acids in bacteria. In yeast, for example, that cutoff limited the list of ORFs to about 6000.

Relaxing that criterion reveals that cells carry vastly more ORFs. Earlier this year, Stanford postdoc Hila Sberro Livnat, Bhatt, and colleagues trawled genome fragments from the microbes that inhabit four parts of the human body, including the gut and skin. By searching for small ORFs that could encode proteins between five and 50 amino acids long, the researchers identified about 4000 families of potential microproteins. Almost half resemble no known proteins, but the sequence for one small ORF suggested that a corresponding protein resides in ribosomesa hint that it could play some fundamental role. "It's not just genes with esoteric functions that have been missed" when scientists overlooked small ORFs, Bhatt says. "It's genes with core functions."

For the first time, we are about to explore this universe of new proteins.

Other cells also house huge numbers of short ORFsyeast could make more than 260,000 molecules with between two and 99 amino acids, for example. But cells almost certainly don't use all those ORFs, and some of the amino acid strings they produce may not be functional. In 2011, after finding more than 600,000 short ORFs in the fruit fly genome, developmental geneticist Juan Pablo Couso of the University of Sussex in Brighton, U.K., and colleagues tried to whittle down the number. They reasoned that if a particular ORF had an identical or near-identical copy in a related species, it was less likely to be genomic trash. After searching another fruit fly's genome and analyzing other evidence that the sequences were being translated, the group ended up with a more manageable figure of 401 short ORFs likely to yield microproteins. That would still represent a significant fraction of the insects' protein repertoirethey harbor about 22,000 full-size proteins.

Weissman and colleagues found microproteins a second way, through a method they invented to broadly determine which proteins cells are making. To fashion any protein, a cell first copies a gene into messenger RNA. Then ribosomes read the mRNA and string together amino acids in the order it specifies. By sequencing mRNAs attached to ribosomes, Weissman and his team pinpoint which ones cells are actually turning into proteins and where on the RNAs a ribosome starts to read. In a 2011Cellstudy, he and his team applied that ribosome profiling method, also called Ribo-seq, to mouse embryonic stem cells and discovered the cells were making thousands of unexpected proteins, including many that would fall below the 100amino-acid cutoff. "It was quite clear that the standard understanding had ignored a large universe of proteins, many of which were short," Weissman says.

Saghatelian and his colleagues adopted a third approach to discover a trove of microproteins in our own cells. The researchers used mass spectrometry, which involves breaking up proteins into pieces that are sorted by mass to produce a distinctive spectrum for each protein. Saghatelian, his then-postdoc Sarah Slavoff, and colleagues applied the method to protein mixtures from human cells and then subtracted the signatures of known proteins. That approach revealed spectra for 86 previously undiscovered tiny proteins, the smallest just 18 amino acids long, the researchers reported in 2013 inNature Chemical Biology.

Being small limitsa protein's capabilities. Larger proteins fold into complex shapes suited for a particular function, such as catalyzing chemical reactions. Proteins smaller than about 50 to 60 amino acids probably don't fold, says chemist Julio Camarero of the University of Southern California in Los Angeles. So they probably aren't suited to be enzymes or structural proteins.

However, their diminutive size also opens up opportunities. "They are tiny enough to fit into nooks and crannies of larger proteins that function as channels and receptors," Olson says. Small proteins often share short stretches of amino acids with their larger partners and can therefore bind to and alter the activity of those proteins. Bound microproteins can also shepherd bigger molecules to new locationshelping them slip into cell membranes, for instance.

A microprotein in the poison of the deathstalker scorpion has been fused to a fluorescent dye to make tumors emit near-infrared light. (1) A tumor seen in visible light (2)Same tumor in visible and near-infrared light

Because of their attraction to larger proteins, small proteins may give cells a reversible way to switch larger proteins on or off. In a 2016 study inPLOS Genetics, plant developmental biologist Stephan Wenkel of the University of Copenhagen and colleagues genetically alteredArabidopsisplants to produce extra amounts of two small proteins. The plants normally burst into flower when the days are long enough, but when they overproduced the two microproteins, their flowering was postponed. The small proteins caused that delay by blocking a hefty protein called CONSTANS that triggers flowering. They tether CONSTANS to other inhibitory proteins that shut it down. "A cell uses things that help it survive. If a short protein does the job, that's fine," Saghatelian says.

Those jobs include other key tasks. In 2016, Slavoff, Saghatelian, and colleagues revealed that human cells manufacture a 68amino-acid protein they named NoBody that may help manage destruction of faulty or unneeded mRNA molecules. NoBody's name reflects its role in preventing formation of processing bodies (P-bodies), mysterious clusters in the cytoplasm where RNA breakdown may occur. When the protein is missing, more P-bodies form, thus boosting RNA destruction and altering the cell's internal structure. "It shows that small proteins can have massive effects in the cell," Slavoff says.

Muscles appear to depend on a variety of microproteins. During embryonic development, individual muscle cells merge into fibers that power contraction. The 84amino-acid protein myomixer teams up with a larger protein to bring the cells together, Olson's team reported in 2017 inScience. Without it, embryonic mice can't form muscles and are almost transparent.

Later in life, myoregulin steps in to help regulate muscle activity. When a muscle receives a stimulus, cellular storage depots spill calcium, triggering the fibers to contract and generate force. An ion pump called SERCA then starts to return the calcium to storage, allowing the muscle fibers to relax. Myoregulin binds to and inhibits SERCA, Olson's team found. The effect limits how often a mouse's muscles can contractperhaps ensuring that the animal has muscle power in reserve for an emergency, such as escaping a predator. Another small protein, DWORF, has the opposite effect, unleashing SERCA and enabling the muscle to contract repeatedly.

Even extensively studied organisms such as the intestinal bacteriumEscherichia coliharbor unexpected small proteins that have important functions. Storz and her team reported in 2012 that a previously undiscovered 49amino-acid protein called AcrZ helps the microbe survive some antibiotics by stimulating a pump that expels the drugs.

And the venom produced by a variety of organismsincluding spiders, centipedes, scorpions, and poisonous mollusksteems with tiny proteins. Many venom components disable or kill by blocking the channels for sodium or other ions that are necessary for transmission of nerve impulses. Small proteins "hit these ion channels with amazing specificity and potency," King says. "They are the major components of venoms and are responsible for most of the pharmacological and biological effects."

Australia's giant fish-killing water bug, for instance, doesn't just rely on sharp claws and lancelike mouthparts to subdue prey. It injects its victims with a brew of more than 130 proteins, 15 of which have fewer than 100 amino acids, King and colleagues reported last year.

Unlike hulking proteinssuch as antibodies, microproteins delivered by pill or injection may be able to slip into cells and alter their functions. Captopril, the first of a class of drugs for high blood pressure known as angiotensin-converting enzyme inhibitors was developed from a small protein in the venom of a Brazilian pit viper. But the drug, which the Food and Drug Administration approved for sale in the United States in 1981, was discovered by chance, before scientists recognized small proteins as a distinct group. So far, only a few microproteins have reached the market or clinical trials.

Cancer researchers are trying to capitalize on a microprotein in the poison of the deathstalker scorpion (Leiurus quinquestriatus) of Africa and the Middle East. The molecule has a mysterious attraction to tumors. By fusing it to a fluorescent dye, scientists hope to illuminate the borders of brain tumors so that surgeons can safely cut out the cancerous tissue. "It lights up the tumor. You can see the margins and if there are any metastases," King says. A clinical trial is now evaluating whether the dual molecule can help surgeons remove brain tumors in children.

How important small proteins will be for medicine is still unknown, but they have already upended several biological assumptions. Geneticist Norbert Hbner of the Max Delbrck Center for Molecular Medicine in Berlin and colleagues found dozens of new microproteins in human heart cells. The group traced them to an unexpected source: short sequences within long noncoding RNAs, a variety that was thought not to produce proteins. After identifying 169 long noncoding RNAs that were probably being read by ribosomes, Hbner and his team used a type of mass spectrometry to confirm that more than half of them yielded microproteins in heart cells, a result reported earlier this year inCell.

Bacteria such as Escherichia coli also churn out many microproteins, although their functions remain unclear in many cases.

The DNA sequences for other tiny proteins also occur in unconventional locations. For example, some lie near the ORFs for bigger proteins. Researchers previously thought those sequences helped manage the production of the larger proteins, but rarely gave rise to proteins themselves. Some coding sequences for recently discovered microproteins are even nested within sequences that encode other, longer proteins.

Those genomic surprises could illuminate how new genes arise, says evolutionary systems biologist Anne-Ruxandra Carvunis of the University of Pittsburgh in Pennsylvania. Researchers had thought most new genes emerge when existing genes duplicate or fuse, or when species swap DNA. But to Carvunis, microproteins suggest protogenes can form when mutations create new start and stop signals in a noncoding portion of the genome. If the resulting ORF produces a beneficial protein, the novel sequences would remain in the genome and undergo natural selection, eventually evolving into larger genes that code for more complex proteins.

In a 2012 study, Carvunis, who was then a postdoc in the lab of Marc Vidal at the Dana-Farber Cancer Institute in Boston, and colleagues found that yeast translate more than 1000 short ORFs into proteins, implying that these sequences are protogenes. In a new study, Carvunis and her team tested whether young ORFs can be advantageous for cells. They genetically altered yeast to boost output of 285 recently evolved ORFs, most of which code for molecules that are smaller than the standard protein cutoff or just over it. For almost 10% of the proteins, increasing their levels enhanced cell growth in at least one environment. The results, posted on the preprint server bioRxiv, suggest these sequences could be on their way to becoming full-fledged genes, Carvunis says.

Slavoff still recalls being astonished when, during her interview for a postdoc position with Saghatelian, he asked whether she would be willing to go hunting for small proteins. "I had never thought that there could be this whole size of proteins that was dark to us until then."

But the bet paid offshe now runs her own lab that is searching for microproteins. Recently, she unleashed some of her postdocs and graduate students on one of the most studied organisms, the K12 strain ofE. coli.The team soon uncovered five new microproteins. "We are probably only scratching the surface," she says.

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New universe of miniproteins is upending cell biology and genetics - Science Magazine