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HOUSTON, Oct. 17, 2019 /PRNewswire/ -- Researchers fromInvitae Corporation (NYSE: NVTA), a leading medical genetics company, are presenting data showing the increasing utility of genetic information at the American Society of Human Genetics (ASHG) annual meeting this week, ranging from comprehensive screening for cancer patients, to appropriate clinical follow up for women using non-invasive prenatal screening, to the limitations of direct to consumer genetic screening health reports.

The company's research includes three platform presentations and multiple poster sessions, many performed in collaboration with leading academic researchers. Among the data presented is a study evaluating the utility of combined germline testing and tumor profiling (somatic testing) in cancer patients. Germline and somatic testing are increasingly used in precision treatment of people with cancer, although frequently are ordered separately in clinical practice. Data presented at the meeting shows a substantial number of patients with medically significant variants in hereditary cancer syndrome genes in their tumor profile carry the same variant in their germline, thereby establishing a previously unknown risk of hereditary cancer and suggesting the value of combined or concurrent testing to inform precision medicine approaches.

"The research we are presenting at this year's ASHG meeting provides meaningful insight into both the science and practice of genetics, helping identify how we as clinicians can better use deep genetic insights to help a wide array of patients, whether they are cancer patients, women having a child or healthy adults seeking to better understand their risk of disease," said Robert Nussbaum, M.D., chief medical officer of Invitae. "We are proud and grateful to be able to join our colleagues from across genetic medicine in meaningful conversations that push genetic medicine forward."

Following are research from the company and collaborators to be presented at the meeting:

Wednesday, October 16:

Poster presentation #819W | 2:00 3:00 pm Germline testing in colorectal cancer: Increased yield and precision therapy implications of comprehensive multigene panels. Presented by Shan Yang, PhD. Invitae.

Poster presentation #2427W | 2:00 3:00 pm Harmonizing tumor sequencing with germline genetic testing: identification of at-risk individuals for hereditary cancer disorders. Presented by Daniel Pineda-Alvarez, MD, FACMG, Invitae.

Poster presentation #606W | 3:00 4:00 pm A comprehensive evaluation of the importance of prenatal diagnostic testing in the era of increased utilization of non-invasive prenatal screening. Presented by Jenna Guiltinan, MS, LCGC, Invitae.

Thursday, October 17:

Platform presentation #235 | 5:00 pm, Room 370A, Level 3 Limitations of direct-to-consumer genetic screening for hereditary breast, ovarian and colorectal cancer risk. Presented by: Edward Esplin, MD, PhD, FACMG, FACP, Invitae.

Poster presentation #763T | 2:00 3:00 pm In-depth dissection of APC pathogenic variants: Spectrum of more than 400 pathogenic variants, challenges of variant interpretation, and new observations in a large clinical laboratory testing cohort. Presented by: Hio Chung Kang, PhD, Invitae.

Poster presentation #1399T | 2:00 3:00 pm Prediction of lethality and severity of osteogenesis imperfecta variants in the triple-helix regions of COL1A1 and COL1A2. Presented by: Vikas Pejaver, PhD, University of Washington.

Friday, October 18:

Platform presentation #264 | 9:00 am, Room 361D, Level 3 Million Veteran Program Return Of Actionable Results - Familial Hypercholesterolemia (MVP-ROAR-FH) Study: Considerations for variant return to mega-biobank participants. Presented by Jason Vassy, MD, MPH, VA, Boston Healthcare System.

Platform presentation #265 | 9:15 am, Room 361D, Level 3 Comprehensive secondary findings analysis of parental samples submitted for exome evaluation yields a high positive rate. Presented by Eden Haverfield, DPhil, FACMG, Invitae.

Poster presentation #698F | 2:00 3:00 pm Reporting of variants in genes with limited, disputed, or no evidence for a Mendelian condition among GenomeConnect participants. Presented by: Juliann Savatt, MS, LGC, Geisinger.

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

Safe Harbor StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the increasing utility of genetic information; the utility of combined germline and somatic testing; and the benefits of the company's research. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the applicability of clinical results to actual outcomes; the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2019. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Contact:Laura D'Angelopr@invitae.com(628) 213-3283

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Research presented by Invitae at the American Society of Human Genetics Meeting Pushes Science and Practice of Genetics Forward - P&T Community

Consumer genetic tests could be giving false reassurance to those at heightened risk of cancers, according to findings presented at an international conference this week.

The study, by clinical genetic testing company Invitae, revealed that tests for breast and bowel cancer risk by direct-to-consumer companies such as 23andMe give negative results to the vast majority of those carrying DNA mutations in the genes under investigation.

These tests should not be taken at face value at all, whether they are positive or negative, said Edward Esplin from Invitae ahead of the annual meeting of the American Society of Human Genetics in Houston, Texas.

The data really underscores that there needs to be increased awareness that results from this type of screening may not be wrong but theyre woefully incomplete.

The research also showed that those from Asian and African-American backgrounds were more likely to carry mutations that were not designed to be detected by the consumer tests.

The research focused on DNA-based tests relating to breast, ovarian and bowel cancer that were recently approved by the US Food and Drug Administration.

The tests operate by a subject sending a DNA swab in the post for analysis and then receiving results with information about how their genetics could influence their health.

In the case of breast and ovarian cancer, the FDA has approved a screening test for three specific mutations on the BRCA1 and BRCA2 genes, which are most common in people of Ashkenazi Jewish heritage. However, these mutations are rare in people from other backgrounds.

Similarly, for bowel cancer, 23andMe offers FDA-authorised tests for two mutations, which are most common among individuals of northern European ancestry. The company explains the limitations of these tests to consumers and on its website.

Esplin said that despite this, consumers could be wrongly reassured by a negative result.

The study analysed the DNA of 270,806 patients who had been referred by healthcare providers for testing of the MUTYH gene, and 119,328 who had been referred for BRCA1/2 genetic testing.

It showed that for both tests, the majority of those carrying mutations would not be spotted, which Invitae describes as a clinical false-negative result.

For MUYTH, 40% of individuals with mutations in both copies of their MUTYH genes consistent with an almost 100% lifetime risk of bowel cancer had different mutations to those screened for in the FDA-approved test. This figure rose to 100% for those from Asian backgrounds and 75% for African-Americans.

For BRCA genes, 94% of non-Ashkenazi Jewish individuals and 19% of those of Ashkenazi heritage had a mutation that would be missed. Again, the figures were highest for those of Asian (98%) and African-American (99%) ancestry. Its performing a disproportionate disservice to individuals of these underrepresented groups, Esplin said.

A clinical false-negative result can be incorrectly reassuring, excluding a patient from receiving the preventive care they need based on their risk, he added. It could be the difference between preventing cancer and developing cancer.

In response to the findings, 23andMe said in a statement: The claims made by a competitor that we are returning clinical false negatives is incorrect and a false characterisation of 23andMes test. Our test is extremely accurate. As part of the FDA authorisation process weve demonstrated over 99% accuracy for the variants we test for in our health product.

The company said it makes clear to customers that it tests only for certain genetic variants and that customers should not forgo any recommended testing based on 23andMe results. 23andMe is not a diagnostic test, the company said. If an individual has a family history of cancer or other indications for clinical testing we always recommend consulting a healthcare provider first.

Prof Anneke Lucassen, a clinical geneticist at the University of Southampton, said that, in her experience, non-specialists would be likely to wrongly interpret negative results as an all-clear.

I do think the false-negative rate is an issue, not necessarily through the companies fault but through low general awareness, she said. Most people who come to clinic ask: Have I got the gene for breast cancer? and imagine its a single test, not that the test involves looking through around 20,000 letters of the genetic code to see if any one of them might be different.

Originally posted here:
Genetic testing kits 'may wrongly reassure those at risk of cancer' - The Guardian

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

Strong signal: One new autism candidate gene is affected solely by variants with unpredictable effects.

Science RF / Adobe Stock

The largest analysis of genetic sequences from autistic people implicates 184 genes in the condition nearly doubling an estimate from last year.

Researchers presented the unpublished results today at the 2019 American Society of Human Genetics meeting in Houston, Texas.

The researchers analyzed sequences of exomes the protein-coding portions of the genome pooled from multiple datasets. They built off their unpublished analysis of nearly 35,000 sequences. That analysis, which the team presented at a conference last year, tied 99 genes to autism.

The new work incorporates 27,000 additional sequences and increases the proportion of autistic people whose condition can be tied to a genetic cause to roughly 20 percent.

The results reflect the rapid increase in the number of sequences and a briskly evolving set of strategies to analyze the data, says Kyle Satterstrom, a computational biologist in Mark Dalys lab at the Broad Institute in Cambridge, Massachusetts, who presented the findings. This is very much a work in progress.

Satterstrom and his colleagues analyzed sequences from nearly 62,000 people. The sample includes 14,473 autistic people and 32,000 of their parents and siblings, as well as an additional 5,556 people with autism and 8,800 controls.

Almost half of the sequences were released in September by SPARK, a project that aims to collect data from 50,000 families. (SPARK is funded by the Simons Foundation, Spectrums parent organization.)

The researchers combed the sequences for rare and possibly spontaneous changes that occur more often than expected in people with autism. They focused on two types of mutations to start with: single-letter variations in DNA and indels, or small insertions or deletions.

They found 39 genes with spontaneous mutations that they say are all but certain to be involved in autism 11 more than appeared on their shortlist of strongest candidates in 2018.

The team then considered a third type of genetic change called a copy number variation (CNV), which involves large insertions or deletions in DNA. They used a statistical tool called TADA to determine which of the genes affected by any of the three types of genetic changes are likely to be involved in autism.

The analysis linked 184 genes to autism with at least 90 percent certainty. Genes that regulate gene expression and communication between neurons two pathways long thought to contribute to autism appear frequently in this list.

One of the new candidates, DEAF1, is affected solely by missense variants single-letter changes to DNA that have effects that are difficult for researchers to predict.

This work will lead the way to many other initiatives to validate candidate genes and demonstrate their [harmful effects], says Giovanni Battista Ferrero, associate professor of pediatrics at the University of Turin in Italy, who was not involved in the study.

Satterstrom says the team is following up onDEAF1 and other promising new candidates. They are also analyzing whole-genome sequences from a subset of the participants.

For more reports from the 2019 American Society of Human Genetics annual meeting, please click here.

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Massive project doubles list of genes tied to autism - Spectrum

Ancestry, the genealogy-focused genetics testing company, on Tuesday announced two new products that will provide consumers with health information based on DNA test resultsa move that places the company "in direct competition with 23andMe," according to STAT News.

What providers need to know about genetic testing and other new clinical innovations

The two AncestryHealth products AncestryHealth Core and AncestryHealth Pluswill look at 17 genes, including:

The products will also test for traits like lactose intolerance and caffeine metabolism. In addition, the tests will include clinical reports that consumers can give to their physicians.

However, the two products provide significantly different services. AncestryHealth Core will provide a one-time report with data based on consumer's DNA microarray. The product will cost consumers $49.

Meanwhile, AncestryHealth Plus will provide a more detailed report to consumers using next-generation DNA sequencing technology. While the AncestryHealth Plus product will initially focus on the 17 genes that the AncestryHealth Core product focuses on, it will technically sequence a consumer's "exome," or" all of the known genes that code for proteins in the body," according to STAT News. However, Ancestry will share only a limited portion of the resulting data with consumers. Consumers interested in the product will pay a one-time fee of $199, plus a $49 subscription fee every six months to receive quarterly reports with updates.

For the new products, Ancestry is teaming up with PWNHealth, a national network of physicians located in New York. For both products, consumers will order a DNA test from the company and complete a survey of their medical history, which is then reviewed by a PWNHealth physician for DNA test approval. The test results, when ready, are then reviewed by PWNHealth providers to ensure that consumers get the right educational materials along with the findingsfor instance, a consumer whose DNA test has potentially worrisome results would also receive an educational video about the condition.

Consumers will also receive video material on DNA testing before getting their results, and, after receiving their results, they will have access to both online resources and, if needed, genetic counselors also from PWNHealth.

According to Business Insider, 23andMe sells many of the same tests Ancestry plans to offer, including reports on carrier status for sickle cell anemia, cystic fibrosis, and Tay-Sachs Diseaseand more than 40 other conditionsfor about $200. 23andMe's tests can also tell consumers if they have an increased risk of Alzheimer's disease or Parkinson's disease, which Ancestry elected not to include.

However, since AncestryHealth will require physicians, rather than consumers, to order the DNA tests, AncestryHealth will operate under CMS' rules for physician-ordered diagnostic testing. In comparison, 23andMe applied for and received FDA approval so that it could make its DNA tests available directly to consumers without a prescription.

Margo Georgiadis, Ancestry's CEO, said the company elected to have doctors order the DNA tests "so that the consumer not only can find out a risk factor, but they can seamlessly take a lab report with clinically recommended guidelines into the doctor's office so that there's a clear next path for action."

Some experts expressed concern over how many genetic diseases the tests will provide information on, and said it's unclear how the patient counseling component of the program will work.

Eric Topol, director and founder of the Scripps Research Translational Institute, voiced concerns about the AncestryHealth Plus product in particular, noting that the American College of Medical Genetics advises providers to share information about harmful mutations in 58 genes with patients who have had their exomes sequenced. The AncestryHealth Plus product is "minimal," he said, adding that while it's "a step in the right direction," it's "not in keeping with consensus and practice in the medical community."

However, Catherine Ball, Ancestry's chief science officer, said the company decided to have its tests focus on only highly actionable diseases because it only wanted to include tests that can "improve outcomes for our customers and for their families."

Separately, David Agus, a professor at the University of Southern California, said, "What people don't get is that genetics are a tiny piece of the puzzle." He noted a study Ancestry and Google published in Genetics that found genes account for less than 10% in differences in people's lifespans.

Laura Hercher, director of research in human genetics at Sarah Lawrence College, said just 2% of patients who don't have a family history of disease would be expected to learn something medically useful from a DNA test. "Some people will get medically useful information from this," she said. But "[f]or most, the idea that DNA testing will help your doctor guide your health decisions is an overstatement" and "premature at best."

Robert Cook-Deegan, a professor at the University of Arizona who studies genome ethics and law, worried that many consumers may not understand their own DNA tests. "A lot of whether this is a good thing or a bad thing depends on the quality of their testing," he said. "It depends on the degree to which those physicians are really involved and the degree to which the genetic counseling is truly incorporated into the process."

Others expressed concerns of whether consumers will know they should be getting a different DNA test than the one they chose. For example, if patients wanted a BRCA1 or BRCA2 test because they had a family history of breast cancer, the AncestryHealth Core test will only tell them if their gene has a common "misspelling," meaning that several specific, cancer-causing mutations could be overlooked, STAT News reports. And while the AncestryHealth Plus test would be more likely spot such an issue if it's present, patients could be better off receiving a DNA test, such as those offered by Myriad Genetics, because those might be covered by insurance.

Robert Green, director of the Genomes2People research program at Brigham and Women's Hospital, said he's concerned patients may wrongly think they're at low risk of a disease because of an incomplete DNA test. "The risk, as with other the consumer genomics, is that patients will think this is somehow a comprehensive and encyclopedic investigation of your entire genomic health," he said. However, he added that "[d]iscovering some people who are carrying significant and actionable mutations is better than finding none of them" (Herper, STAT News, 10/15; Ramsey, Business Insider, 10/15; Brown, Bloomberg, 10/15).

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Ancestry will offer health DNA tests, setting its sights on 23andMe - The Daily Briefing

CDC officials say they're not sure why younger people who are having less sex are acquiring more STDS, but a new bill moving through the House to increase spending on STD prevention could help. Public health news is on CBD, pros and cons of genetic tests, limiting sports time for teens, childhood obesity, insecticides, getting young kids hooked on sugar, smart aging, and dementia, as well.

The Wall Street Journal:Public-Health Puzzle: Young People Having Less Sex, Contracting More STDsIt sounds contradictory: Young people, were told, are having less sex than older generations did at the same age. But theyre also contracting more sexually transmitted diseases than any other group, and the rates of infection are accelerating at an alarming pace. Last year, combined cases of syphilis, gonorrhea and chlamydia reached an all-time high with half the reported infections occurring in adolescents and young adults ages 15 to 24. (McGinty, 10/18)

Stateline:CBD May Be Natural, But Is It Safe?Hemp cannabidiol (CBD), a cannabis extract largely unknown a few years ago, has become so popular that some Americans take a spoonful every day. People are vaping CBD, drinking CBD-infused coffee and snacking on CBD-infused chocolates in the hopes of easing their aches, pains and anxiety. But the health benefits of cannabidiol are unclear, and many products hitting the market havent been made in clean, permitted facilities or tested for toxic pesticides, heavy metals and bacteria, according to state officials, hemp businesses and news reports. (Quinton, 10/19)

NPR:Genetic Tests For Psychiatric Drugs Now Covered By Some InsurersAs a teenager, Katie Gruman was prescribed one mental health drug after another. None seemed to help her manage symptoms of anxiety and bipolar disorder, so she self-medicated with alcohol and illicit drugs. It would take five years, and trying more than 15 different medications, before she found meds that actually helped. (Dangor, 10/17)

Stat:Competitor Accuses 23andMe Of 'False Negatives' In Cancer-Gene TestingWhen 23andMe received government permission in 2017 to sell health-related genetic testing, it came with several conditions, including that the company tell customers that its brand of testing can miss disease-causing variants. Now, in a study presented on Thursday at the annual meeting of the American Society of Human Genetics, a competitor has analyzed the likelihood of such false negatives, concluding that in some ethnic groups the chance that 23andMes tests will miss a cancer-causing DNA variant is 100%. 23andMe pushed back hard on that conclusion from DNA testing company Invitae (NVTA). It is patently wrong to state that 23andMe delivers false negatives for variants that it does not test nor claim to test for, said a company spokesman. This is a false and misleading characterization of 23andMes test. (Begley, 10/17)

The New York Times:Parents Should Limit Sports Participation For Children, Trainers SayToo many children are risking injuries, even lifelong health problems, because they practice too intensively in a single sport, and parents should set limits on their participation, according to a leading organization of athletic trainers. New recommendations issued by the National Athletic Trainers Association urge parents to ensure that children and adolescents postpone specializing in one sport for as long as possible, that they take at least two days off each week for rest and that they not play a single sport for more than eight months a year. (Rabin, 10/17)

WBUR:Childhood Obesity Is Rising 'Shockingly Fast' Even In Poor CountriesHigh rates of childhood obesity are a problem in a rising number of low- and middle-income countries, according to a new global assessment of child malnutrition by UNICEF. It's the agency's most comprehensive nutrition report in two decades. The report paints a complex, dire picture of the state of children's health. (McDonnell, 10/17)

The New York Times:A Nazi Version Of DDT Was Forgotten. Could It Help Fight Malaria?What if, after the Allies won World War II, world health officials had employed a Nazi version of DDT against mosquitoes that transmit malaria? Could that persistent disease, which still infects more than 200 million people a year and kills 400,000 of them, have been wiped off the planet? That is one of the musings of chemists at New York University who came across an insecticide that had been developed by German scientists during World War II in the course of conducting abstract research on another topic. (Chang, 10/17)

The Washington Post:How The Baby Food Industry Hooks Low-Income Toddlers On Sugar, Salt And FatLeading health organizations recently released their first consensus recommendations about what young children should be drinking: only breast milk or, if necessary, infant formula until a baby is six months old, with water introduced around then, and plain cows milk at around their first birthday. Thats it. No juice, no flavored or plant-based milks, no caffeinated beverages or sodas. The good news is parents of infants seem to be on the right track breastfeeding is on the rise. But once children get into the toddler zone, its pandemonium. (Reiley, 10/17)

The New York Times:Youre Only As Old As You FeelNot long ago, Stephanie Heller, a New Jersey realtor, was leaving her gym after a workout when she noticed a woman in the parking lot struggling to bend down. I dont know if she dropped something and had to pick it up, or if her shoe was untied, Ms. Heller said, but she eagerly bounded over to help. The woman blamed old age for her incapacity, explaining that she was 70. But Ms. Heller was 71. (Laber-Warren, 10/17)

The New York Times:Can Personality Affect Dementia Risk?Your personality in high school may help predict your risk of dementia decades later. Researchers reached this conclusion using a 150-item personality inventory given to a national sample of teenagers in 1960. The survey assessed character traits sociability, calmness, empathy, maturity, conscientiousness, self-confidence and others using scores ranging from low to high. For their study, in JAMA Psychiatry, scientists linked the scores of 82,232 of the test-takers to Medicare data on diagnoses of dementia from 2011 to 2013. (Bakalar, 10/17)

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What's Behind Rise Of STDS Among Young People?: Epidemic Alarms Health Officials As Prevention Funding Drops - Kaiser Health News

AUSTIN, Texas, Oct. 16, 2019 /PRNewswire/ -- L7 Informatics, Inc. ("L7"), a leading software and analytics company for healthcare and life science companies, announces the completion of the Phase 1 implementation of its Enterprise Scientific Platform (ESP) with CReATe Fertility Centre. CReATe, which stands for Canadian Reproductive Assisted Technology is headquartered in Toronto, Canada, and is internationally renowned for its specialized fertility services and ground-breaking research. The organization was seeking a scientific information management platform to streamline and optimize their genomics testing operations.

"We are very honored to be chosen to work with CReATe, they are leaders in the field of assisted reproductive technologies with state-of-the-art laboratory facilities and pioneering research scientists," said L7 CEO & President, Vasu Rangadass, Ph.D. "In connection with these high standards, we feel ESP is the ideal platform to streamline the overall Reproductive genomic lab processes by integrating with multiple laboratory instruments, managing complex sample provenance, managing sample storage, inventory, and automating a multitude of important tasks such as bar code printing and clinical report generation."

This project is being completed in four phases and focuses on configuring workflow chains and supporting models (sample types, procedures, etc.) to support four of the array of tests performed by CReATe Reproductive Genomic Lab: PGT-A, PGT-M/PGT-SR, POC testing, and Focused carrier screening. L7's ESP fosters process orchestration and expedites clinical diagnostics by building an integrated, instrument agnostic platform to manage scientific processes and data in one place and yielding better access to the data and results.

"L7's ESP has enabled us to bring patient clinical information from our EMR at the click of a button, and to track laboratory operations meeting OLA and CAP regulations, using its powerful audit trail and provenance history capabilities," mentioned Svetlana Madjunkova MD, PhD., Director of Reproductive Genetics Department at CReATe. Adding, "It's truly a game-changer and will contribute to the advancement of our IVF clinical operations and research."

L7 Informatics and CReATe are also excited to announce that they will be speaking together about their work at the upcoming 2019 American Society of Human Genetics (ASHG) Conference in Houston, Texas. They will partake in a Data CoLabs presentation titled "IVF in silico: fertilization assistance by facilitating clinical and research collaboration" on Wednesday, October 16th at 12:45 pm in CoLab Theatre 2 on the exhibit floor. Robert Zeigler, Ph.D., Director of Customer Solutions for L7 and Dr. Madjunkova will walk the audience through the project, highlighting best-in-class practices.

About L7 InformaticsOur mission is to revolutionize scientific information management to accelerate discoveries and drive higher quality of healthcare. Our end-to-end solutions and services yield efficiencies that enable researchers to make more breakthroughs and healthcare companies to provide superior care. To learn more about L7's Enterprise Science Platform, please go to https://www.l7informatics.com/esp/

About CReATe IVFCReATe Fertility Centre mission is to provide state of the art and compassionate care in a safe environment for our patients and staff; undertake innovative research and provide excellent teaching and mentorship. To learn more about CReATe Fertility Centre, please go to https://www.createivf.com/

Media Contact:Jessica TobeySpeaks Marketing Group LLCJessica@Speaksmarketing.com

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Software and Analytics Company to Deploy Cutting Edge Platform for Leading Fertility Organization - P&T Community

It's estimated that every three minutes, somewhere in the world a baby is born with a cleft lip or palate, making it one of the most common birth defects.

Eighteen-year-old Emma Johnston was born with a cleft palate and has been in and out of hospital her entire life for surgeries and speech therapy.

"I was very aware growing up that my face did look different because of that, the way that my jaw fit together, it was just very different to other people's," she said.

Babies born with a completely clefted palate often need surgery to avoid lifelong problems with speech, eating and hearing.

Emma Johnston got to know her surgeons and doctors very well over the years of her treatment.

(Supplied: Emma Johnston)

Emma Johnston got to know her surgeons and doctors very well over the years of her treatment.

While a minor cleft lip may not require surgical treatment, it can still affect someone's quality of life if they feel uncomfortable or are bullied about their appearance.

Emma was born with an isolated cleft palate, which meant she had no cleft lip or other abnormalities other than the open palate.

She had her first palate surgery when she was just nine months old, and has had nine operations just to put grommets in her ears.

"Surgeries, as much as I'm used to them, they're not fun, they're not pleasant," she said.

To understand what cleft palate is, you have to understand the palate which is essentially the roof of your mouth.

The soft palate is at the back of the mouth ending in the uvula, which is the teardrop-shaped bit of soft tissue that dangles down.

(Getty Images: Christoph Wilhelm)

The soft palate is at the back of the mouth ending in the uvula, which is the teardrop-shaped bit of soft tissue that dangles down.

Getty Images: Christoph Wilhelm

The hard palate is the bony plate at the front of the roof of your mouth, directly behind your upper teeth, and it helps move food back through the mouth.

Your soft palate is at the back of the mouth and is made up of soft muscle which closes against the back wall of the throat when swallowing, blocking the nasal passage.

The soft palate is also the working mechanism for speech, closing and opening depending what type of sound is being made to let air out.

Clefting of the lip or palate happens when there is an incomplete fusion of the palate development in the womb typically in the sixth to eighth week of pregnancy that results in an opening in the upper lip, palate, or both. It can vary in its severity.

"Cleft palate is an abnormal gap or opening in the roof of the mouth," explained plastic and reconstructive surgeon Vani Prasad.

"It can be very minor, just a change in the shape of the lip, or a small scar from the lip to the nose.

"It can be incomplete cleft lip meaning the lip has a visible gap, but the nose is not affected, or if it's complete, the cleft can affect the nose and extend into the gum."

As is the case for Emma, a cleft palate can be isolated not accompanied by a cleft lip. In others the cleft palate and lip can occur together.

"We do see babies with soft and hard cleft palate, plus a complete cleft lip," said Dr Prasad, who's based at the Australian Craniofacial Unit in Adelaide.

Cleft lip and palate management usually involves a multidisciplinary team of medical staff including surgeons, speech therapists, dentists and psychologists.

(Getty Images: China Photos)

Cleft lip and palate management usually involves a multidisciplinary team of medical staff including surgeons, speech therapists, dentists and psychologists.

Getty Images: China Photos

The extent of the clefting, and whether the palate or lip is cleft in isolation can determine treatment and management, as well as the impact it has on quality of life.

Being born with a cleft palate can affect speech, hearing, the ability to eat, as well as physical appearance not to mention the potential for being a frequent flyer at the hospital or doctor's office.

But Emma's doctors are hopeful her most recent surgery is her final surgery on her palate.

Emma's cleft palate meant that sometimes food and spit would come back out her nose, because the palate didn't close against the back of her throat.

(Supplied: Emma Johnston)

Emma's cleft palate meant that sometimes food and spit would come back out her nose, because the palate didn't close against the back of her throat.

Her surgeon, Dr Mark Moore from the Australian Craniofacial Unit, said 18-year-old Emma's palate was working hard when she spoke, but not going far enough to close the space with the back of her throat.

"We had to look at operations to make her palate longer," Dr Moore said.

"We made a cut in her palate along the soft palate and then made cuts on either side like a 'z' - like Harry Potter sort of on the forehead."

The surgery was successful and Emma was thrilled to be finished with her surgeries.

"I really wanted to see the seal in the back of my throat to know that I was doing that properly, it was brilliant," she said.

"On the outside I don't look any different to anyone else, now all the surgeries are done.

"It's terrifying, but it's a good terrifying. It's amazing."

As is the case with many babies with cleft palate, Emma had difficulty breastfeeding, which was one of the motivations to operate within a year of her birth.

Another reason for doing the cleft lip or palate repair operation early is to allow more time for proper speech development.

If the initial repair surgery is delayed it can impede speech development.

But the timing of cleft lip and palate repair is a subject of some controversy in the medical community, because a compromise has to be made regarding risk, facial growth, scarring, and psychological factors.

Most plastic surgeons think the ideal age for undergoing cleft palate repair surgery is between 6 to 18 months of age, and even earlier for cleft lip repair.

(Supplied: Chris Sprod)

Most plastic surgeons think the ideal age for undergoing cleft palate repair surgery is between 6 to 18 months of age, and even earlier for cleft lip repair.

Not everyone can have surgery for cleft palate or lip repair early in life though.

This is particularly an issue in developing countries in Asia, where the one in every 500 babies has a cleft palate and lip compared to one in 1,000 in white populations.

"In the past in some Asian countries, it's been because of a deficiency in folic acid," Dr Prasad said.

"A deficiency in folic acid can cause increased risk of neural tube defects, which can increase risk of cleft palate or craniofacial disorders," he said.

Dr Prasad said that pregnant women taking anti-convulsive medication for epilepsy can also have increased risk of their baby having cleft palate or lip.

Going through the process of cleft repair surgery with your baby can be hard, but Dr Prasad and his colleagues try to encourage parents to be positive about the change they are experiencing, as well as that of their baby.

"We tell parents of babies with cleft lip to think of their baby as getting to have two different smiles," he said.

"They have one smile before the repair surgery, and a different one after the surgery, so we tell them to enjoy both of their baby's smiles."

Scientists are still trying to narrow down the causes of cleft lip and palate, but research suggests there is some sort of genetic link.

In 2018, scientists identified four genes that, when functioning correctly, lead to the tissues around the hard palate becoming 'sticky' and fusing together the two sides of the palate.

The study, published in the American Journal of Human Genetics, focused on families in which multiple people were affected by cleft lip or palate, suggesting there could be an alteration within a single gene, said Tony Roscioli from Neuroscience Research Australia, who was an author on the study.

"We were able to identify specific gene mutations that were present in people with cleft lip palate in a number of families," Dr Roscioli said.

"A single genetic cause that was highly predictive."

Of the 209 people from 72 families in the study, the four genes accounted for the cleft palate or lip in 15 per cent of them, a small but significant step forward in understanding the genetic causes of clefting, according to Dr Roscioli.

"It is premature for [finding specific treatments], but perhaps ways of altering the function of these genes could be identified in the future that could lead to non-surgical treatments," he said.

Dr Roscioli was involved in another study published this year in the journal Human Mutations which identified one new gene that causes a form of cleft palate that's associated with skeleton abnormalities, and another new gene that causes isolated cleft lip and palate.

"It increases the number of genes known but also [suggests] that the genes work together," he said.

"It can also mean that there are extra genes available for people who wish to have genetic testing for cleft lip and palate."

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Cleft palate or lip is one of the most common birth defects worldwide, but do you know what it is? - ABC News