StemCell Therapy

This article, written byMichael Mackley, Dalhousie University, originally appeared on The Conversation and is republished here with permission:

Youve likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you dont find a DNA testing kit under your own Christmas tree, theres a good chance someone you know will.

Whether youre motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users and important personal implications that consumers should consider.

Health, traits and ancestry kits

My main area of research is around clinical genome sequencing, where we look through all of a persons DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared. Another option is Living DNA, which has a smaller dataset but provides more precise information on the U.K. and Ireland.

The most popular health kit is from 23andMe. Depending on the users preference, results include information on predispositions for diseases such as diabetes and Alzheimers, as well as on the likelihood of having certain traits such as hair colour and taste. This company also offers ancestry analysis, as well as ancestry and trait-only kits that dont provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

How these tests work

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to survey the users genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group. For example, if your results say that you are 42 per cent Southeast Asian, its because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled Southeast Asian. The same goes for traits and health conditions.

How they differ from clinical tests

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

Before you spit in a tube, stop and think

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. Theyre also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service youre using, and determine whether youre comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Bottom line: Its all for fun

Some users may feel they learn more about themselves. For others, results may bring people closer together not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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DNA tests might be a fun holiday gift, but beware of the hype - HalifaxToday.ca

Based on the results of the pivotal HER2CLIMB Trial (NCT02614794) presented at the 42nd San Antonio Breast Cancer Symposium (SABCS) held in San Antonio, Texas, December 10 14, 2019, and data published in the New England Journal of Medicine (NEJM), Seattle Genetics confirmed that the company completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tucatinib.

Tucatinib is an investigational, oral, small molecule tyrosine kinase inhibitor (TKI). Tyrosine kinases are enzymes that are a part of many cell functions, including cell signaling, growth, and division. But in some cases they may be too active or found at high levels in some types of cancer cells. In that case, blocking them may help keep cancer cells from growing.

Tucatinib is highly selective for HER2.

HER2-positive breast cancerPatients with HER2-positive breast cancer have tumors with high levels human epidermal growth factor receptor 2 (HER2), a protein which promotes the aggressive spread of cancer cells.

According to the American Cancer Society, in the United Stated, an estimated 271,270 new cases of invasive breast cancer were diagnosed in in 2019.[1] In addition, based on the available data, between 15% and 20% of all diagnosed breast cancer cases worldwide are HER2-positive.[2]

Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.[2][3][4]

In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.[5][6] In about 50% of metastatic HER2-positive breast cancer cases, patients develop brain metastases over time. [2][7]

Although there have been many advances in the treatment of metastatic HER2-positive breast cancer, there is still a significant unmet medical need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression following treatment with trastuzumab emtanzine.[8][9][10]

Combination therapyIn their NDA, Seattle Generics requested the FDA to approve tucatinib in combination with capecitabine (Xeloda; Genentech/Roche) and trastuzumab (Herceptin; Genentech/Roche) for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting.

This setting is the same setting for which the investigational drug was recently granted Breakthrough Therapy designation by the FDA and included patients with brain metastases, who have been treated with trastuzumab, pertuzumab (Perjeta; Genentech/Roche), and trastuzumab emtanzine (Kadcyla; Genentech/Roche).

HER2CLIMB TrialThe HER2CLIMB study is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial included data from 612 enrolled patients.

The trial results published in the NEJM, presented at the SABCS by Rashmi K. Murthy, M.D., assistant professor of Breast Medical Oncology, demonstrated that tucatinib significantly improved progression free survival (PFS) and overall survival (OS) in patients with advanced HER2-positive breast cancer, with and without brain metastasis.

The trial met its primary endpoint of the study demonstrated that the treatment combination reduced the risk of death by 46% compared with trastuzumab and capecitabine alone. The trial also met its secondary endpoints at interim analysis, demonstrating prolonged OS, reduced the risk of death by 34% and extended PFS by 52% among patients with brain metastasis.

Furthermore, with 41%, the overall response rate was higher in the tucatinib group compared with 23% in the standard of care treatment.

This is a uniquely designed trial in that it allowed patients to enroll if they had untreated, treated stable or previously treated, but progressive brain metastasis, Murthy noted.

Brain metastasizes are common in up to half of patients during the disease course, but there are limited systemic treatment options because most available agents have difficulty crossing the blood brain barrier, she added.

Well toleratedThe study results demonstrated that the triplet combination of tucatinib + capecitabine + trastuzumab was generally well tolerated with no unexpected toxicities. In the tucatinib arm the investigators observed diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, all mostly low grade, as the reported adverse events. Furthermore, there was a low drug discontinuation rate of 5.7% in the triplet arm compared with 3% in the control arm.

This trial verified that tucatinib is both a safe and effective treatment, Murthy explained during the SABCS.

These results are realy unprecedented for late line therapy in locally advanced, metastatic, breast cancer. This is a major treatment advance for patients who have significant unmet medical need. I believe that tucatinib in combination with trastuzumab and capecitabine could be the new standard of care for patients pretreated with multiple anti-HER2 agents including patients with brain metastasis, Murthy said.

Todays submission marks another important milestone for Seattle Genetics and tucatinib, and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, MD, Chief Medical Officer at Seattle Genetics.

We look forward to working with the FDA on the review of this application, he concluded.

Clinical trialsTucatinib, Trastuzumab, and Capecitabine for the Treatment of HER2+ LMD NCT03501979A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer NCT03975647A Study of Tucatinib vs. Placebo in Combination With Capecitabine & Trastuzumab in Patients With Advanced HER2+ Breast Cancer (HER2CLIMB) NCT02614794

References[1] American Cancer Society, Cancer Facts and Figures 2018-2019.[2] Loibl S, Gianni L (2017). HER2-positive breast cancer. The Lancet 389(10087): 2415-29.[3] Slamon D, Clark G, Wong S, et al. (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785): 177-82.American Cancer Society (ACS) (2018). Breast cancer HER2 status. Last accessed: December 20, 2018.[4] Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology 28(20): 3271-7.[5] Berman AT, Thukral AD, Hwang W-T, et al. (2013). Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment. Clinical Breast Cancer 13(2): 88-94.[6] Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treatment Reviews 67: 71-7.[7] Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 367(19): 1783-91.[8] Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 355(26): 2733-43.[9] Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. Journal of Clinical Oncology 30(21): 2585-92.

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Seattle Genetics Submits New Drug Application to the US FDA for Tucatinib - OncoZine

GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work.

While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor's journal.

The editors make decisions quickly in around 35 days without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists.

GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook . For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we've published thematic collections, including Genomic Prediction, Multiparental Populations, Genetics of Immunity, and Genetics of Sex.

More than just a publisher, the Genetics Society of America is mission-driven and places a high priority on responding to community needs. GENETICS and G3 have long been committed to supporting resources that serve scientists. We were the first journals to partner with Cold Spring Harbor Laboratories to enable seamless deposits of manuscripts from our submission systems straight into the preprint server bioRxiv, as well as from bioRxiv to GENETICS and G3, and we have accepted submissions posted for preprint servers since 2012. Articles feature links to model organism databases like SGD, FlyBase, and WormBase. We have also partnered with Overleaf to provide custom templates for authors who use LaTex, saving them time at submission. Our collaboration with protocols.io, encourages authors to freely share methods from GENETICS articles, helping to increase research reproducibility. The annotation tool Remarq is available on both the GENETICS and G3 websites and allows for collaborative commenting and article sharing. Our latest collaboration with Figshare ensures that supplemental material and data files are permanently associated with an articleand that authors arent limited by file type or size when providing data that support their work. Early online publication means that research investigations are freely accessible and in PubMed within days of acceptance which eliminates delays in discovering the latest science.

For information on the Genetics Society of America, please visit the GSA Home Page.

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About GENETICS | Genetics

Learn about the building blocks of life and the future of medicine.

The way we diagnose and treat diseases is changing, with new technologies enabled by a deeper understanding of the human genome and its relationship to health and disease.

In HMX Fundamentals Genetics, youll get an overview of key concepts behind the evolving fields of human genetics, genomics, and precision medicine.

For upcoming course dates and application information, visit our Courses page.

Experience a full genetics lesson in the HMX Preview course.

Overview

The Central Dogma and Genetic Variation

Mendelian Inheritance of Disease

Identifying Mendelian Disease Genes

Chromosomal Aberrations

The Genetics of Cancer

Common Complex Traits

Human Population Genetics

Beyond the Genome Sequence

Genetics and Precision Medicine

Lecturer in Genetics, Harvard Medical School

As DNA sequencing becomes cheaper and more readily available, the role of genetics in medicine is expanding. With our increasing understanding of the variation in the human genome, we can start to predict how specific changes in DNA sequence will affect an individuals health. Human genetics is extremely complicated, but it is apparent that many human diseases are influenced by genetics. From a medical perspective, this includes everything from rare DNA sequence variants that drastically increase risk of a disease, to common variants that lead to small changes in risk.

Historically, genetics specialists have helped patients to navigate these situations, but genetics is beginning to permeate medicine as a whole. This means that health care professionals across many fields are faced with new questions. When do you recommend genetic testing to a patient? What kind of testing will provide the most conclusive results? How do you help the patient to understand those results, and use them to make decisions about his or her care? Moving forward, an understanding of the principles of genetics and an ability to apply them in todays medical landscape will be an enormous asset for any health care professional.

Even outside of medicine, genetics has a very important presence in our world today, so, fundamentally, what I would like students to take away from this course is a level of genetic literacy that will allow them to navigate the questions and decisions that they will face in their own lives.

Direct-to-consumer genetic testing now allows everyone to learn about their own genetics; these tests can potentially include information about health and disease risk and ancestry that have significant impacts for individuals and their families. When making decisions about genetic testing, it is important to be informed about exactly what you will learn and what the consequences of the results might be down the line.In this course, we put the fundamental principles of human genetics into the context of the world today, which will provide students with the tools and resources to ask the right questions and make informed genetic decisions.

Professor of Medicine, Harvard Medical SchoolAssociate Physician, Brigham and Womens HospitalGeneticist, Brigham and Womens HospitalDirector, Genomes2People Research Program at Brigham and Womens Hospital

Genomics is inherently exciting, and you can see that because of its relationship to forensic law enforcement, reproduction, ancestry, cancer and all sorts of medical developments, and all of the controversy related to direct-to-consumer genetic testing.

The skeleton of genetics is sequencing, and people are building on that with gene expression, proteomics, metabolomics. So there are multiple layers of knowledge and exploration that are generating tremendous excitement in the world, and motivating enormous investment scientifically, educationally, financially, and entrepreneurially. So the question isnt really why Im interested in genomics, the question is why isnt everybody interested in genomics because its so fabulously interesting.

Senior Genetic Counselor and Project Manager, Brigham & Womens Hospital

Genetics is really a subspecialty of all specialties. The more we understand the genetic basis of biology, the more we will understand human health and disease. Having a strong background in genetics will be important as genomic technologies continue to expand and are implemented more and more into clinical care. Understanding how to look for patterns of disease and when to refer a patient to other specialists is an important tool for every health care provider, and as more patients have genetic results in their medical records, having the ability to understand how this is or is not important to your patients medical care will be of the utmost importance. Overall a global knowledge of genetics will help you to provide better care to your future patients.

I hope students are able to grasp some of the basic concepts about genetics and to understand why it is a vital part of medical care. I hope that this background knowledge will be useful to them if and when they care for patients who come to them with a genetic test result, a family history of genetic disease or a presenting genetic diagnosis. I hope this course excites them about the concept of genetics and genomics and encourages them to want to learn more as their career progresses.

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Genetics - HMX | Harvard Medical School

Experimental breeding

Genetically diverse lines of organisms can be crossed in such a way to produce different combinations of alleles in one line. For example, parental lines are crossed, producing an F1 generation, which is then allowed to undergo random mating to produce offspring that have purebreeding genotypes (i.e., AA, bb, cc, or DD). This type of experimental breeding is the origin of new plant and animal lines, which are an important part of making laboratory stocks for basic research. When applied to commerce, transgenic commercial lines produced experimentally are called genetically modified organisms (GMOs). Many of the plants and animals used by humans today (e.g., cows, pigs, chickens, sheep, wheat, corn (maize), potatoes, and rice) have been bred in this way.

Britannica Quiz

Branches of Genetics

Which is the study of the influence that genes and traits have on habits and actions?

Cytogenetics focuses on the microscopic examination of genetic components of the cell, including chromosomes, genes, and gene products. Older cytogenetic techniques involve placing cells in paraffin wax, slicing thin sections, and preparing them for microscopic study. The newer and faster squash technique involves squashing entire cells and studying their contents. Dyes that selectively stain various parts of the cell are used; the genes, for example, may be located by selectively staining the DNA of which they are composed. Radioactive and fluorescent tags are valuable in determining the location of various genes and gene products in the cell. Tissue-culture techniques may be used to grow cells before squashing; white blood cells can be grown from samples of human blood and studied with the squash technique. One major application of cytogenetics in humans is in diagnosing abnormal chromosomal complements such as Down syndrome (caused by an extra copy of chromosome 21) and Klinefelter syndrome (occurring in males with an extra X chromosome). Some diagnosis is prenatal, performed on cell samples from amniotic fluid or the placenta.

Biochemistry is carried out at the cellular or subcellular level, generally on cell extracts. Biochemical methods are applied to the main chemical compounds of geneticsnotably DNA, RNA, and protein. Biochemical techniques are used to determine the activities of genes within cells and to analyze substrates and products of gene-controlled reactions. In one approach, cells are ground up and the substituent chemicals are fractionated for further analysis. Special techniques (e.g., chromatography and electrophoresis) are used to separate the components of proteins so that inherited differences in their structures can be revealed. For example, more than 100 different kinds of human hemoglobin molecules have been identified. Radioactively tagged compounds are valuable in studying the biochemistry of whole cells. For example, thymine is a compound found only in DNA; if radioactive thymine is placed in a tissue-culture medium in which cells are growing, genes use it to duplicate themselves. When cells containing radioactive thymine are analyzed, the results show that, during duplication, the DNA molecule splits in half, and each half synthesizes its missing components.

Chemical tests are used to distinguish certain inherited conditions of humans; e.g., urinalysis and blood analysis reveal the presence of certain inherited abnormalitiesphenylketonuria (PKU), cystinuria, alkaptonuria, gout, and galactosemia. Genomics has provided a battery of diagnostic tests that can be carried out on an individuals DNA. Some of these tests can be applied to fetuses in utero.

Physiological techniques, directed at exploring functional properties or organisms, are also used in genetic investigations. In microorganisms, most genetic variations involve some important cell function. Some strains of one bacterium (Escherichia coli), for example, are able to synthesize the vitamin thiamin from simple compounds; others, which lack an enzyme necessary for this synthesis, cannot survive unless thiamin is already present. The two strains can be distinguished by placing them on a thiamin-free mixture: those that grow have the gene for the enzyme, those that fail to grow do not. The technique also is applied to human cells, since many inherited human abnormalities are caused by a faulty gene that fails to produce a vital enzyme; albinism, which results from an inability to produce the pigment melanin in the skin, hair, or iris of the eyes, is an example of an enzyme deficiency in man.

Although overlapping with biochemical techniques, molecular genetics techniques are deeply involved with the direct study of DNA. This field has been revolutionized by the invention of recombinant DNA technology. The DNA of any gene of interest from a donor organism (such as a human) can be cut out of a chromosome and inserted into a vector to make recombinant DNA, which can then be amplified and manipulated, studied, or used to modify the genomes of other organisms by transgenesis. A fundamental step in recombinant DNA technology is amplification. This is carried out by inserting the recombinant DNA molecule into a bacterial cell, which replicates and produces many copies of the bacterial genome and the recombinant DNA molecule (constituting a DNA clone). A collection of large numbers of clones of recombinant donor DNA molecules is called a genomic library. Such libraries are the starting point for sequencing entire genomes such as the human genome. Today genomes can be scanned for small molecular variants called single nucleotide polymorphisms, or SNPs (snips), which act as chromosomal tags to associated specific regions of DNA that have a property of interest and may be involved in a human disease or disorder.

Many substances (e.g., proteins) are antigenic; i.e., when introduced into a vertebrate body, they stimulate the production of specific proteins called antibodies. Various antigens exist in red blood cells, including those that make up the major blood groups of man (A, B, AB, O). These and other antigens are genetically determined; their study constitutes immunogenetics. Blood antigens of man include inherited variations, and the particular combination of antigens in an individual is almost as unique as fingerprints and has been used in such areas as paternity testing (although this approach has been largely supplanted by DNA-based techniques).

Immunological techniques are used in blood group determinations in blood transfusions, in organ transplants, and in determining Rhesus incompatibility in childbirth. Specific antigens of the human leukocyte antigen (HLA) genes are correlated with human diseases and disease predispositions. Antibodies also have a genetic basis, and their seemingly endless ability to match any antigen presented is based on special types of DNA shuffling processes between antibody genes. Immunology is also useful in identifying specific recombinant DNA clones that synthesize a specific protein of interest.

Because much of genetics is based on quantitative data, mathematical techniques are used extensively in genetics. The laws of probability are applicable to crossbreeding and are used to predict frequencies of specific genetic constitutions in offspring. Geneticists also use statistical methods to determine the significance of deviations from expected results in experimental analyses. In addition, population genetics is based largely on mathematical logicfor example, the Hardy-Weinberg equilibrium and its derivatives (see above).

Bioinformatics uses computer-centred statistical techniques to handle and analyze the vast amounts of information accumulating from genome sequencing projects. The computer program scans the DNA looking for genes, determining their probable function based on other similar genes, and comparing different DNA molecules for evolutionary analysis. Bioinformatics has made possible the discipline of systems biology, treating and analyzing the genes and gene products of cells as a complete and integrated system.

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Genetics - Methods in genetics | Britannica

If, then, progress was to be made in Genetics, work of a different kind was required.

It sprang from genetics and bears the mark of an implicit Darwinian mechanism.

The metaphors of genetics and evolutionary models can be applied.

I've been studying up on biology and genetics; talking to Chang got me interested.

Lindstrom of Iowa has led in research on the genetics of tomatoes, chromosome relations and mode of inheritance.

Most students of genetics realize that a factor difference usually affects more than a single character.

The formalism of memetics reminds many of us of formal languages, as well as of the shorthand used in genetics.

General biology and the science of Genetics are bringing to light much that must be incorporated in Sociology.

The terminology is based on today's fashionable lingo of genetics, and of memetics, its counterpart.

They also opened new horizons for hypotheses in astronomy, genetics, anthropology.

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Genetics Synonyms, Genetics Antonyms | Thesaurus.com

Genetics is a field of scientific study focused on heredity and DNA variation. Genetics professionals need a strong background in biological science to support their work, and most positions in this field require graduate degrees. Learn more about genetics and relevant career options here.

Genes are composed of DNA, the molecule that determines a living thing's unique physical characteristics, such as hair color or immunity to certain diseases. Geneticists are the biological scientists who study genes and how genetic variations affect the body. The job duties of genetics professionals vary by setting. While clinical geneticists and genetics doctors work directly with patients, genetic scientists spend most of their time in research or laboratory settings.

Many careers in this field require doctoral degrees in genetics or closely related fields; however, options are available to those who hold relevant bachelor's or master's degrees. Many geneticists focus their careers on research and laboratory study and typically hold Ph.D.s in genetics, molecular biology or related fields of study.

Geneticists may also serve as clinical geneticists, physicians who provide medical care to patients suffering from hereditary diseases. Clinical geneticists must complete medical school and obtain licensure to practice as physicians. Below is a list of Study.com articles to help you choose the degree program that's right for you.

While online degree programs in genetics are rare, some schools offer correspondence courses that lead to college credit. Students may be able to complete courses or earn degrees in biology and other genetics-related subjects.

While becoming a geneticist is the obvious career path, a variety of other career options are also available for students who do not possess a doctoral degree. Individuals with a master's degree in a related branch of counseling may become genetic counselors, providing therapeutic services to patients who have been diagnosed with hereditary diseases.

With a master's degree in genetics, a student might find employment as a laboratory research assistant. A bachelor's degree related to genetics may also qualify a graduate for a job as a laboratory technician. Here are a few links to articles that may help you discover which career you want to pursue.

According to the U.S. Bureau of Labor Statistics (BLS), jobs for biological scientists were expected to increase 19 percent from 2012-2022, faster than the average for other occupations (www.bls.gov). Advances in research have uncovered new information on genes, and more genetics professionals will be needed to develop medical treatments out of this new information. Although employment rates in this field fluctuate according to government funding and economic climate, the BLS reports that biological scientists, such as geneticists, are less prone to job loss caused by recessions.

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Genetics - Study.com

It hasn't been the best quarter for Myriad Genetics, Inc. (NASDAQ:MYGN) shareholders, since the share price has fallen 20% in that time. In contrast the stock is up over the last three years. However, it's unlikely many shareholders are elated with the share price gain of 47% over that time, given the rising market.

Check out our latest analysis for Myriad Genetics

While markets are a powerful pricing mechanism, share prices reflect investor sentiment, not just underlying business performance. One flawed but reasonable way to assess how sentiment around a company has changed is to compare the earnings per share (EPS) with the share price.

Over the last three years, Myriad Genetics failed to grow earnings per share, which fell 37% (annualized).

Thus, it seems unlikely that the market is focussed on EPS growth at the moment. Therefore, we think it's worth considering other metrics as well.

It could be that the revenue growth of 4.2% per year is viewed as evidence that Myriad Genetics is growing. In that case, the company may be sacrificing current earnings per share to drive growth, and maybe shareholder's faith in better days ahead will be rewarded.

You can see below how earnings and revenue have changed over time (discover the exact values by clicking on the image).

NasdaqGS:MYGN Income Statement, December 24th 2019

It's good to see that there was some significant insider buying in the last three months. That's a positive. On the other hand, we think the revenue and earnings trends are much more meaningful measures of the business. So we recommend checking out this free report showing consensus forecasts

Investors in Myriad Genetics had a tough year, with a total loss of 8.9%, against a market gain of about 40%. Even the share prices of good stocks drop sometimes, but we want to see improvements in the fundamental metrics of a business, before getting too interested. Unfortunately, last year's performance may indicate unresolved challenges, given that it was worse than the annualised loss of 6.9% over the last half decade. Generally speaking long term share price weakness can be a bad sign, though contrarian investors might want to research the stock in hope of a turnaround. If you want to research this stock further, the data on insider buying is an obvious place to start. You can click here to see who has been buying shares - and the price they paid.

Myriad Genetics is not the only stock insiders are buying. So take a peek at this free list of growing companies with insider buying.

Please note, the market returns quoted in this article reflect the market weighted average returns of stocks that currently trade on US exchanges.

If you spot an error that warrants correction, please contact the editor at editorial-team@simplywallst.com. This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. Simply Wall St has no position in the stocks mentioned.

We aim to bring you long-term focused research analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Thank you for reading.

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Does Myriad Genetics's (NASDAQ:MYGN) Share Price Gain of 47% Match Its Business Performance? - Yahoo Finance

You've likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you don't find a DNA testing kit under your own Christmas tree, there's a good chance someone you know will.

Whether you're motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work - before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users - and important personal implications that consumers should consider.

My main area of research is around clinical genome sequencing, where we look through all of a person's DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared.

Another option is Living DNA, which has a smaller dataset but provides more precise information on the UK and Ireland.

The most popular health kit is from 23andMe. Depending on the user's preference, results include information on predispositions for diseases such as diabetes and Alzheimer's, as well as on the likelihood of having certain traits such as hair colour and taste.

This company also offers ancestry analysis, as well as ancestry and trait-only kits that don't provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

A direct-to-consumer DNA testing kit. (Shutterstock)

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to "survey" the user's genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group.

For example, if your results say that you are 42 per cent Southeast Asian, it's because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled "Southeast Asian." The same goes for traits and health conditions.

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. They're also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service you're using, and determine whether you're comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Some users may feel they learn more about themselves. For others, results may bring people closer together - not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read more here:
DNA Tests Make a Fun Gift But Here's What You Need to Know Before You Unwrap - ScienceAlert

According to news articles published in early December, Veritas Genetics, a Massachusetts-based company that hoped to lower the cost of whole-genome sequencing, is suspending its U.S. operations because of a lack of investment. Articles theorize that the decreased funding was driven mainly by new CFIUS regulations and heightened CFIUS scrutiny.

Early in December 2019, Veritas announced that its adverse financing situation had forced the suspension of its U.S. business. Veritas has stated that it is assessing potential paths forward, and there are rumors that one such path is the sale of the company. Veritas will no longer sell its tests, which include genetic testing for diseases and cancers (such as the BRCA test), in the United States. Veritas will continue to operate and sell its tests outside the United States.

Veritas first launched in 2014, and since 2015 it had raised $50 million in financing. Major investors included Chinese companies, such as Lilly Asia Ventures, which invested $10 million into the company, and Simcere Pharmaceutical. However, there has been increased scrutiny in the past two years for transactions that involve Chinese investors, especially when sensitive personal information, such as genetic information, is at stake. This year, for example, CFIUS forced iCarbonX, the Chinese, majority owner of U.S. company PatientsLikeMe, to divest its stake in the U.S. company.

According to news reports, recent CFIUS activity may have scared away not only Chinese investors but also non-Chinese investors reluctant to invest in a company with Chinese ownership. Non-Chinese investors may fear that Veritass Chinese ownership will lead to increased CFIUS scrutiny of any investment into Veritas, regardless of the investors nationality. Investors may also worry that CFIUS scrutiny could delay their return on investment if their firms are forced to stall business to address CFIUSs concerns.

No doubt the proposed CFIUS regulations from September also concern foreign investors: the proposed regulations explicitly target U.S. companies that maintain or collect sensitive personal data of U.S. citizens. While most sensitive personal data only triggers the proposed regulations if the U.S. business maintains or collects such data on greater than one million individuals, companies with genetic data are considered to be covered businesses no matter how many individuals are involved. Thus, companies like Veritas will always fall under CFIUS jurisdiction if a foreign person would acquire certain rights in the company. These rights include:

Several genetic and biopharmaceutical companies expressed concern in public comments to the regulations that the proposed regulations, specifically including all genetic data in the definition of sensitive personal data, would stymie foreign investment in these companies. Several companies argued that the Department of the Treasury should revise the proposed CFIUS regulations to require that genetic data be identifiable. Companies often are in possession of anonymized genetic information, which these companies argued does not pose a risk to national security. We await publication of the final regulations and whether CFIUS will make any changes to the definition of sensitive personal data, particularly as it pertains to genetic information. It is to be seen whether U.S. companies in other industries will face similar funding obstacles as foreign investors grow more wary of CFIUS.

Original post:
Veritas, a US Genetic Sequencing Company, Suspends US Operations Due to Decreased Funding; CFIUS Thought to be Leading Cause - Lexology

It always comes back to haunt you.

Thats what Union County Sheriff Brad Whitehead says of crime in general, after his office helped detectives in Colorado arrest a suspect, at last, in a 40-year-old rape-murder case.

On January 16, 1980, Helene Pruszynski a 21-year-old radio intern was raped and murdered in a vacant field in Douglas County, Colo. Her body was found the next morning.

Finding a suspect would take much longer.

It was a combination of DNA, existing technology that was available, but then the dogged police work, 18th Judicial District Attorney (CO) George Brauchler said at a press conference almost 40 years later, upon the arrest and formal charging of James Curtis Clanton, now 62.

It was an investigation that turned up occasional suspects but just as many dead ends. Clanton, who at the time of Pruszynskis death went by the name Curtis Allen White, had been convicted of rape in Arkansas in 1975 but was paroled less than four years later. He also was arrested in Palm Beach County, Fla. on a domestic battery charge in 1998.

But despite DNA found at the crime scene, investigators couldnt connect Clanton to the crime in Colorado, at least not until some of those dead ends spawned different approaches.

RELATED: Florida man charged with murder, kidnapping in 1980 death of Colorado radio intern

In one key instance, investigators had begun to suspect a man named William White Jr., who had a criminal history. Whites DNA would prove to be an imperfect match with evidence at the Pruszyinski murder scene and he was cleared. But then detectives used a relatively new technique called genetic genealogy, which allows investigators to essentially climb "up" a family tree from an eliminated suspect to ancestors often with the help of online DNA databases to find viablesuspects among common descendants. It would turn out, White and Clanton are brothers.

Eventually, it was determined that Clanton was living in Lake Butler, Fla. and had resided there at least a decade. According to Whitehead, Clanton had no encounters with local law enforcement during those years.

In a town where Whitehead says many people grow up together and know each other, it wasnt difficult to learn that Clanton was a regular at the Full House Lounge on Fourth Avenue.

He was always a laid-back, cool guy," Tom Christakes told First Coast News at a bar. "I dont know him other than just coming here and playing pool.

Christakes added that hed been acquainted with Clanton for about five years.

I actually taught him how to bank playing pool, just a couple weeks ago,: he said. But Im, like, completely shocked.

Investigators in Douglas County, Col. asked the Union County Sheriffs Office to try getting a sample of Clantons DNA. Thats when a deputy who knew the owner of the Full House Lounge arranged a plan to retrieve a beer mug after Clanton used it. The mug was retrieved Nov. 30.

Within days, Whitehead says a DNA match was confirmed. Police arrested Clanton without incident at his home Dec. 11.

He parked his truck where he normally always does, Douglas County Sheriff Tony Spurlock said in a press conference Dec.16. Got out of his truck and was walking away from it, when he was taken in to custody.

Whitehead added, I believe once he saw us, that he felt like he knew his past had caught up with him.

Clanton was extradited to Colorado, where he was formally charged with four murder-related counts and one of kidnapping on Monday, Dec. 16. The District Attorneys office in Colorados 18th judicial district tells First Coast News its still considering whether to pursue the death penalty against Clanton.

Whatever that decision will be, District Attorney Brauchler offered a stern-yet-satisfied summation of Clantons arrest particularly the modern methods that he says solved the cold case.

There are crimes yet unsolved today that I have great optimism because of cases like this, that were going to end up solving, Brauchler told the media. And I think the public ought to feel good about that, and I think murderers ought to be scared to death of it.

In a statement on Facebook, a woman named Janet Johnson, who says Helene Pruszynski was her sister, asked that her familys privacy be respected, offering the following statement:

"I want people to know what a special person Helene was. My sister was my best friend. She was a loving daughter, sister, aunt, & friend. Helene was on track to do great things, she had a bright future ahead of her. There has not been a day that goes by that we haven't missed her. The detectives and everyone else who helped to make this day happen are my heroes. I look forward to justice being served.

More here:
'I think murderers ought to be scared to death of it...' Genetic genealogy leads to arrest of Florida man in 40-year-old cold case murder -...

This article, written byMichael Mackley, Dalhousie University, originally appeared on The Conversation and is republished here with permission:

Youve likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you dont find a DNA testing kit under your own Christmas tree, theres a good chance someone you know will.

Whether youre motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users and important personal implications that consumers should consider.

Health, traits and ancestry kits

My main area of research is around clinical genome sequencing, where we look through all of a persons DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared. Another option is Living DNA, which has a smaller dataset but provides more precise information on the U.K. and Ireland.

The most popular health kit is from 23andMe. Depending on the users preference, results include information on predispositions for diseases such as diabetes and Alzheimers, as well as on the likelihood of having certain traits such as hair colour and taste. This company also offers ancestry analysis, as well as ancestry and trait-only kits that dont provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

How these tests work

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to survey the users genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group. For example, if your results say that you are 42 per cent Southeast Asian, its because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled Southeast Asian. The same goes for traits and health conditions.

How they differ from clinical tests

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

Before you spit in a tube, stop and think

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. Theyre also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service youre using, and determine whether youre comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Bottom line: Its all for fun

Some users may feel they learn more about themselves. For others, results may bring people closer together not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read the rest here:
BEYOND LOCAL: DNA tests might be a fun holiday gift, but beware of the hype - TimminsToday

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced it has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tucatinib. This NDA requests FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting. The submission is based on the results of HER2CLIMB, a randomized pivotal trial comparing tucatinib added to trastuzumab and capecitabine versus trastuzumab and capecitabine alone. HER2CLIMB trial results were presented on December 11, 2019 at the 2019 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.

Todays submission marks another important milestone for Seattle Genetics and tucatinib, and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. We look forward to working with the FDA on the review of this application.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab, and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline, and confirmed objective response rate. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1, 2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal, and gastric cancers. HER2 mediates cell growth, differentiation, and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate, and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic, or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival, and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

About Seattle Genetics

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops, and commercializes transformative medicines targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) and PADCEV (enfortumab vedotin-ejfv) use the companys industry-leading antibody-drug conjugate (ADC) technology designed to bring a powerful medicine directly to cancer cells. ADCETRIS is approved for the treatment of several types of CD30-expressing lymphomas, and PADCEV is approved to treat adults with metastatic urothelial cancer. In addition, investigational agent tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer, and in clinical development for metastatic colorectal cancer. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland, and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential FDA approval of tucatinib in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting; the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses and anticipated development activities including ongoing and future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that the New Drug Application submission based on the HER2CLIMB trial may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all or with the requested label; the difficulty and uncertainty of pharmaceutical product development; the risk of adverse events or safety signals; and the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

References:

Follow this link:
Seattle Genetics Announces Submission of Tucatinib New Drug Application to the U.S. FDA for Patients with Locally Advanced or Metastatic HER2-Positive...

Here we are at the end of yet another year, a year that definitely went by faster than the year before or for that matter the year before that. And as ever at this time of year tis the season for casting ahead and divining what the future holds, delivering lists of top 10s and predictions of what will be hot and what will not.

In some fields, the resultant list will look very much like something delivered by the toss of a coin, but in the science and research areas it is pretty certain what will land in the top two or three subjects.

Number one has got to be climate and the impact of global warming. There is no other area that can match it for the variety and depth of research activity being applied to a whole range of climate-related subjects. And the hard news stories keep tumbling out of this endeavour, helping to show that global changes are taking place due to the alterations in climate that we as humans have set in motion.

One peer-reviewed study about the increasingly rapid loss of ice mass over Greenland was published less than a fortnight before Christmas. It showed that the biggest block of land ice in the northern hemisphere was melting away much faster than expected, seven times faster the study suggests.

Published in the journal Nature, it said the island lost 33 billion tonnes of ice on average during the last decade of the 20th century but the average annual ice loss for the most recent 10 years now stands at 254 billion tonnes of ice a year.

This is just one story and one research area, but climate-related studies arise in many fields from alteration of ocean currents to changed rainfall patterns and from species loss to poor air quality. It is also a subject area that affects us all given the potential of coastal flooding, crop losses and human migration to name but a few possible future impacts.

The impacts for humanity are also there in research into new ways to alter our genetic blueprints. The key to unlocking the potential to overcome gene-based diseases relates CRISPR CAS9, our current best technology for getting into the genome and then adding, deleting or altering individual genes.

It has the potential to reverse disease states by correcting unwanted mutations. It is being used in labs around the world as scientists seek to fully understand the method and apply it to alter genes. It is a powerful research tool, for example to create a mouse model that imitates a human disease state and then developing and testing drugs that might be used in humans. It also allows the researcher to look for any unwanted downstream effects arising from genetic alterations.

There are so many scientists using the CRISPR tools that news reports and discoveries will certainly follow. Yet most research scientists are concerned about the lack of controls or limits on what kind of genetic experiments that might be conducted on the human genome. Too little is known about unexpected problems if a number of genes are altered to eliminate a genetic disorder.

There is also the issue of genetic alteration of the germline, the genetic material that moves across to the next generation. There is currently an international block on germline alterations but that has not stopped at least one researcher who went ahead and created the worlds first two genetically modified humans. Breakthroughs will be delivered all through 2020 it is probably safe to say.

What might come third in this short list is up for grabs, and what might produce the next big scientific discovery could come from any direction. For that reason this report becomes a wish list relevant to Irish research and scientific endeavour related to our engagement with important international research bodies.

One of the most important decisions in this regard brings us closer to membership of Cern, Europes premier nuclear research body. A Dil committee studied the research and commercial potential arising from membership and called on the Government to join Cern as quickly as possible.

Cerns huge atom smasher confirmed the existence of the Higgs Boson, an international effort that involved many countries. Ireland could become more involved in this kind of research if it were a member. The Government has already taken the leap and announced our membership of the European Southern Observatory.

Our astronomers and physicists can now get access to some of the worlds largest telescopes based in Chile. The ESO is also a mill for discoveries and this membership gives us the potential to become international players in this field. And in more familiar territory, the Government has renewed its commitment to invest 100 million in the European Space Agency between now and 2024, a decision that ensures Ireland can bid for commercial contracts and researchers can participate in ESA activities. Our investment pays for itself given Irish companies can share in contracts.

All of the research areas mentioned here show how important it is to internationalise Irelands involvement in science. By doing this, we give more opportunities to promising young Irish scientists and help build a strong international reputation for research. Certainly that is not too much to ask for this Christmas.

Originally posted here:
Another year of climate change, genetics and Irish scientific ambition - The Irish Times

Biodiversity the variation in all living organisms is one of Africas richest assets. As a result, its genetic material is coveted by scientists, biotechnology companies and research institutes globally. For decades, there has been a flow of data and biosamples from the African continent to the global north. This has often been in the absence of legitimate participant consent, community engagement or data or material transfer agreements.

Biopiracy the act of directly or indirectly taking undue advantage of research participants and communities in global health research has a long and contentious history in Africa. A recent case occurred during the West African Ebola outbreak between 2014 and 2016 when thousands of biological specimens left the continent without consent. Very often there is minimal benefit sharing.

The issue has been in the news again in South Africa. Accusations have been levelled against the Wellcome Sanger Institute in the UK for allegedly attempting to commercialise data obtained from various African universities. This has reignited questions around models of consent in research, donor rights, biopiracy and genomic sovereignty.

The latest revelations show that legislation as well as academic research governance bodies have failed to adequately safeguard the rights of vulnerable participants in genomics research.

One missing piece of the puzzle is the limited empirical data on the views of people whose biosamples are taken in the name of research. This would include issues of ownership, future use, export, benefit-sharing and commercialisation.

In 2011 and 2012 we surveyed participants to better understand their views. We recruited participants who had experience with research, the consent process and use of biological samples. They were engaged in studies at academic research units attached to public hospitals and private research centres.

Our findings remain relevant today as many of the issues raised by the people we spoke to have still not been addressed.

Our study was conducted over a 10 month period from September 2011 to June 2012. We sampled 200 participants in the Western Cape and Gauteng provinces in South Africa. Participants who had already consented to use of their blood for research were asked several questions including the following: how they felt about their samples being stored for future use and about them being sent abroad to foreign countries, as well as the possibility of future commercialisation.

Most participants were supportive of research. But many expressed concerns about export of their blood samples and data out of South Africa.

For their part, researchers viewed the biosamples as donations. But participants believed they had ownership rights and were keen on benefit sharing. Almost half of the participants were not in favour of broad consent delegated to a research ethics committee. Their preference was to be contacted again for consent in the future.

The legitimacy of using broad consent models for genomic research and biobanking occupies a contested space among bioethicists and researchers globally. Broad consent allows researchers to use biosamples and data indefinitely for future research.

Usually, with broad consent, future research must be approved by a Research Ethics Committee (a diverse group of experts from different research, medical, legal and ethics disciplines) and it is then not necessary to contact donors and ask for their permission to conduct research with their samples or data again.

But this type of consent is particularly contentious in resource depleted countries. This is because research participants often dont understand the complex scientific jargon used in consent documents or processes, especially where use of their samples or data in the future is concerned. This includes commercialisation.

Strong privacy protection legislation and other similar laws require specific consent. This means that individual participants need to consent to use of their data in a specific project or disease category. This makes it challenging to understand how broad consent (delegated to a research ethics committee) for unspecified future use can be legally obtained in research.

This is particularly concerning where future commercialisation may be included in broad consent models without being explicitly discussed with participants. The language used to explain commercialisation is often vague and not fully comprehensible by vulnerable populations.

South Africa also has protocols in place. For example, clear, explicit, voluntary informed consent is required for all use of data and samples belonging to research participants. If data or samples are to be transferred to other researchers in South Africa or abroad, participants ought to be aware of this and can then consent or decline. However, this is not always what happens.

In addition, if data is to be shared with another institution, a data transfer agreement or material transfer agreement must be signed prior to the transfer. This too does not always happen.

South Africa needs to up its game and reform governance around research ethics. This is particularly necessary in the context of international collaborative research. Good governance needs to incorporate transparency, fairness and honesty.

Research ethics committees and researchers need to ensure that data transfer agreements or material transfer agreements are in place prior to sharing of samples or data.

More importantly, community representatives on research ethics committees should be empowered to review consent documents to establish if appropriate language is used to explain commercialisation and data or sample sharing.

A tiered consent model gives participants choice in terms of how their data or samples could be used in the future. This happens when participants choose what they agree to in the consent document. It also allows for specific choices to be voiced on benefit sharing for participants or their respective communities.

In addition, authentic community engagement with co-creation of knowledge production and benefit sharing is essential to ensure equity in global research.

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Africa's genetic material is still being misused - The Conversation Africa

BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tucatinib, in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. The positive topline results of the pivotal HER2CLIMB clinical trial were announced in October 2019, and additional data were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 11, 2019 and were simultaneously published in the New England Journal of Medicine (NEJM). Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The FDAs Breakthrough Therapy process is intended to expedite the development and review of promising drug candidates intended for serious or life-threatening conditions. Designation is based upon preliminary clinical evidence of the potential for substantial improvement over existing therapies on one or more clinically significant endpoints.

The addition of tucatinib to the commonly used combination of trastuzumab and capecitabine demonstrated superior activity compared to trastuzumab and capecitabine alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases, said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. The decision by the FDA to grant Breakthrough Therapy designation to tucatinib recognizes the urgent need for new medicines that can impact the lives of those with HER2-positive metastatic breast cancer. We intend to submit a New Drug Application to the FDA and an MAA to the EMA by the first quarter 2020, with the goal of making tucatinib available to patients in this setting as soon as possible.

This Breakthrough Therapy designation was based on data from the pivotal HER2CLIMB clinical trial, which compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients had received a median of four prior lines of therapy overall and three in the metastatic setting. Forty-seven percent of the patients enrolled in the trial had brain metastases at the time of enrollment.

Data presented at SABCS and published in NEJM include the primary endpoint of progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. The primary endpoint of PFS showed that the addition of tucatinib was superior to trastuzumab and capecitabine alone, with a 46 percent reduction in the risk of disease progression or death (hazard ratio (HR)=0.54 (95% Confidence Interval (CI): 0.42, 0.71); p<0.00001). The trial met the two key secondary endpoints at interim analysis. The tucatinib arm demonstrated an improvement in overall survival, with a 34 percent reduction in the risk of death (HR=0.66 [95% CI: 0.50, 0.88]; p=0.0048), compared to the control arm. For patients with brain metastases at baseline, the tucatinib arm also demonstrated superior PFS, with a 52 percent reduction in the risk of disease progression or death, compared to the control arm (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).

Tucatinib in combination with trastuzumab and capecitabine was generally well tolerated. The most common adverse events occurring in more than 20 percent of patients in the tucatinib arm vs. the control arm included diarrhea, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting. Discontinuation of tucatinib and placebo due to adverse events was 5.7 percent in the tucatinib arm and 3.0 percent in the control arm. Greater than or equal to Grade 3 diarrhea was seen in 12.9 percent of the patients in the tucatinib arm vs. 8.6 percent in the control arm. Antidiarrheal prophylaxis was not required per protocol. Antidiarrheals were used in less than half of all cycles where diarrhea was reported. In both treatment arms, when used, the duration of antidiarrheal treatment was short (median of 3 days/cycle). Greater than or equal to Grade 3 aspartate aminotransferase (AST) was seen in 4.5 percent of the patients in the tucatinib arm vs. 0.5 percent in the control arm, and alanine aminotransferase (ALT) elevation in 5.4 percent vs. 0.5 percent, respectively. Discontinuations due to liver transaminase elevations were infrequent in both arms (ALT: 1.0 vs. 0.5 percent; AST: 0.7 vs. 0.5 percent).

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is progression-free survival per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. The trial is being conducted in North America and is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is objective response rate by RECIST criteria. Progression-free survival, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at http://www.clinicaltrials.gov.

About Seattle Genetics

Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) utilizes the companys industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company has a late-stage pipeline including enfortumab vedotin for metastatic urothelial cancer, currently being reviewed for approval by the FDA, and tisotumab vedotin in clinical trials for metastatic cervical cancer, which utilize our proprietary ADC technology. In addition, tucatinib, a small molecule tyrosine kinase inhibitor, is in late-stage development for HER2-positive metastatic breast cancer and in clinical development for metastatic colorectal cancer. We are also leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of tucatinib, including its possible efficacy, safety and therapeutic uses; anticipated development activities including ongoing and future clinical trials; and intended regulatory actions, including the plan to submit an NDA to the FDA and a MAA to the EMA by the first quarter of 2020. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the possibility of disappointing results in ongoing or future clinical trials despite earlier promising clinical results, the possibility of delays in the submission of an NDA to the FDA and a MAA to the EMA, the possibility that data from the HER2CLIMB trial may not be sufficient to support approval of tucatinib, the possibility of adverse regulatory action. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

References:

1. American Cancer Society, Cancer Facts and Figures 2018-2019.

2. Loibl S, Gianni L (2017). HER2-positive breast cancer. The Lancet 389(10087): 2415-29.

3. Slamon D, Clark G, Wong S, et al. (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785): 177-82.

4. American Cancer Society (ACS) (2018). Breast cancer HER2 status. Accessed: December 10, 2018.

5. Kennecke H, Yerushalmi R, Woods R, et al. (2010). Metastatic Behavior of Breast Cancer Subtypes. Journal of Clinical Oncology 28(20): 3271-7.

6. Berman AT, Thukral AD, Hwang W-T, et al. (2013). Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment. Clinical Breast Cancer 13(2): 88-94.

7. Duchnowska R, Loibl S, Jassem J (2018). Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treatment Reviews 67: 71-7.

8. Verma S, Miles D, Gianni L, et al. (2012). Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 367(19): 1783-91.

9. Geyer CE, Forster J, Lindquist D, et al. (2006). Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. New England Journal of Medicine 355(26): 2733-43.

10. Blackwell KL, Burstein HJ, Storniolo AM, et al. (2012). Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. Journal of Clinical Oncology 30(21): 2585-92.

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Seattle Genetics Announces U.S. FDA Grants Breakthrough Therapy Designation for Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast...

Diversity starts at the gene level

Natural killer (NK) cells are immune cells with potent antiviral and antitumor activities. These cells express several germline-encoded inhibitory receptors (KIRs) that prevent NK cells from killing healthy cells but enable the targeting of infected and transformed cells. Using various imaging techniques and functional assays, Kennedy et al. investigated the effects of genetic diversity in KIR-encoding genes on receptor organization and activity. They found that KIRs encoded by distinct genes were present at varying abundances and in clusters of varying sizes, which led to differences in downstream signaling that affected NK cell function. Together, these data suggest that genetic diversity in KIR-encoding genes affects receptor organization, signaling, and functional outcomes.

Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs encoded by different genes and alleles were organized differently at the surface of primary human NK cells. KIRs that were found at low abundance assembled into smaller clusters than those formed by KIRs that were more highly abundant, and at low abundance, there was a greater proportion of KIRs in clusters. Upon receptor triggering, a structured interface called the immune synapse assembles, which facilitates signal integration and controls NK cell responses. Here, triggering of low-abundance receptors resulted in less phosphorylation of the downstream phosphatase SHP-1 but more phosphorylation of the adaptor protein Crk than did triggering of high-abundance receptors. In cells with greater KIR abundance, SHP-1 dephosphorylated Crk, which potentiated NK cell spreading during activation. Thus, genetic variation modulates both the abundance and nanoscale organization of inhibitory KIRs. That is, as well as the number of receptors at the cell surface varying with genotype, the way in which these receptors are organized in the membrane also varies. Essentially, a change in the average surface abundance of a protein at the cell surface is a coarse descriptor entwined with changes in local nanoscale clustering. Together, our data indicate that genetic diversity in inhibitory KIRs affects membrane-proximal signaling and, unexpectedly, the formation of activating immune synapses.

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Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors - Science

Over the past few years most Americans have been more and more curious about their family trees thanks to kits like 23 and Me and Ancestry.com. But did you know your DNA could be used to solve cold cases, convict people whove committed violent crimes, and even exonerate the wrongfully accused?One local genealogist explains why this seeming harmless gift could unlock a world of answered questions for law enforcement.Closure, is the driving force behind genetic genealogists Shera LaPoint.To be able to give that gift to some one has changed my life. Its the most rewarding thing Ive ever done.

Throughout the years she has closed dozens of cold cases thanks familial DNA but the popularity of DNA testing groups like 23 and Me, have a lesser known option that can be beneficial to law enforcement.

As a tester you have a right to decide what information you want to put out there and who its shared with.

Users can also opt into sharing their DNA with officers helping them in several ways, thanks to new technology.

By uploading your DNA you never know who you will be actually helping. We can take these criminals off the streets, we can exonerate innocent people, we can identify John and Jane Does, and also the fallen military who are unnamed, said LaPoint.They can use my DNA or someone I manage that has agreed to opt in, to help capture a dangerous individuals, then I really dont have a problem, says Mark Richard.

Mark Richard, supports opting into sharing DNA with law enforcement because he says it can close dark chapters in peoples lives.

Richard adds, sometimes these are unsolved crimes where families can not get closure. People dont know what happened from an incident you know someone got murdered or raped and people never know who did it. Then these cases go cold because they didnt have the DNA back then so this is giving families an opportunity for closure.Then you give a DNA kit as a Christmas gift, think about going the extra mile and giving a little bit extra by uploading your DNA. Opting into law enforcement use, and lets make a difference in this world, said LaPoint.Aside from working on cold cases, Shera also uses genetic geology to connect adoptees with their parents . For more information about Shera and all her works, click here.

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Genetic Genealogy Helping Law Enforcement Close Cold Cases and More - News15 | Lafayette, LA - FOX 15

1. Apple is offering free genetic tests to all its Silicon Valley employees  CNBC
2. Apple to offer free genetic testing for employees, report says  Business Insider
3. Apple partners with Color to provide free genetics tests to employees  Becker's Hospital Review
4. Apple Offers Free Genetic Testing to Cupertino Employees  MacRumors
5. Apple's AC Wellness offering free genetic testing to employees  AppleInsider
6. View full coverage on Google News

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Apple is offering free genetic tests to all its Silicon Valley employees - CNBC

In a new study, a high genetic risk score (GRS) was associated with an increased risk of organ damage, renal (kidney) dysfunction and mortality in people with lupus. Organ damage, cardiovascular disease, proliferative nephritis (kidney lesions), end-stage renal disease (ESRD) and presence of antiphospholipid antibodies were successfully predicted by a high GRS in people with lupus. GRSs have been applied in several fields of medicine and may be a potential tool for prediction of disease severity in lupus.

Clinical data from 1,001 people with lupus were analyzed. Their health outcomes and cumulative genetic risk were compiled and compared against the GRSs of 5,524 people with lupus and 9,859 healthy people. Lupus was more prevalent in the high-, compared with the low-GRS group Patients in the high GRS group had a 6-year earlier average disease onset, displayed higher prevalence of damage accrual, ERSD, proliferative nephritis, certain types of autoantibodies and positive lupus anticoagulant test, compared with patients in the low-GRS group. Survival analysis showed earlier onset of the first organ damage, first cardiovascular event, nephritis, ESRD and decreased overall survival in people with high GRSs compared to those with low scores.

Genetic profiling may be useful for predicting outcomes in people with lupus and aid in the clinical decision process. Understanding the genetic contribution to permanent organ damage is important for understanding how lupus develops. Learn more about the genetics of lupus.

Read the study

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Genetic Risk Scores May Predict Severity and Outcomes in People with Lupus - Lupus Foundation of America