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In a unique twist on human genomics studies that seek to identify genetic variants linked to human disease, researchers have combined whole-exome sequencing of 50,726 adults with the individuals' long-term electronic health record (EHR) data. The effort, by researchers at the Geisinger Health System in Pennsylvania and Regeneron Genetics Center, a subsidiary of New York-based Regeneron Pharmaceuticals, has yielded novel disease-linked variants, including loss-of-function alleles. The team behind the project, called DiscovEHR, has also found that about one in 30 of the individuals harbors a deleterious genetic variant for which a screen or treatment already exists. The group's analysis is described in two papers published today (December 22) in Science.

A worldwide study of the DNA of 100,000 women has discovered two new genetic variants associated with an increased risk of breast cancer. The genetic variants are specifically linked to the most common form of breast cancer, oestrogen receptor positive, and provide important insights into how the disease develops.

Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a "risk" allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders.

Genetic differences among ethnically diverse individuals are largely due to structural elements called copy number variants (CNVs), according to a study published today (August 6) in Science. Compared with other genomic features, such as single nucleotide variants (SNVs), CNVs have not previously been studied in as much detail because they are more difficult to sequence. Covering 125 distinct human populations around the world, geneticist Evan Eichler at the University of Washington in Seattle and an international team of colleagues studied the genomes of 236 people-analyzing both SNVs and CNVs. "The take-home message is that we continue to find a lot more genetic variation between humans than we appreciated previously," Eichler told The Scientist.

A new study, published on Wednesday in Molecular Biology and Evolution, identifies gene variants in Inuit who live in Greenland, which may help them adapt to the cold by promoting heat-generating body fat. These variants possibly originated in the Denisovans, a group of archaic humans who, along with Neanderthals, diverged from modern humans about half a million years ago.

In 2007, researchers discovered that people with a common variant of FTO tend to be heavier than those without it. Since then, studies have repeatedly confirmed the link. On average, one copy of the risky variant adds up to 3.5 extra pounds of weight. Two copies of the gene bring 7 extra pounds - and increase a person's risk of becoming obese by 50 percent.

In population genetics, gene flow (also known as gene migration) is the transfer of alleles or genes from one population to another. Migration into or out of a population may be responsible for a marked change in allele frequencies (the proportion of members carrying a particular variant of a gene). Immigration may also result in the addition of new genetic variants to the established gene pool of a particular species or population.

This biomarker, called the KRAS-variant, is linked to more cancers than any other known inherited genetic mutation. It is present in 1 out of every 4 people with cancer, and in more than half of people who develop multiple cancers. KRAS-variant carriers tend to get highly aggressive and recurrent breast, ovarian, head and neck, lung and pancreatic cancers.

High heritability points to a major role for inherited genetic variants in the aetiology of schizophrenia7, 8. Although risk variants range in frequency from common to extremely rare9, estimates10, 11 suggest half to a third of the genetic risk of schizophrenia is indexed by common alleles genotyped by current genome-wide association study (GWAS) arrays. Thus, GWAS is potentially an important tool for understanding the biological underpinnings of schizophrenia

This directed case study was developed in order to present genomic data to students, allow them to interpret the impact of genetic variations on phenotype, and to explore precision medicine. Students are introduced to "Josie," a college sophomore who decides to have her genome sequenced after learning about genome-wide association studies (GWAS) in class. As students work  through the case, they learn about the different technologies that can be used in GWAS studies and interpret Josie's results for a subset of genetic markers that affect a range of traits from pharmacogenetics to disease risk alleles and non-pathogenic traits. Students are confronted with ethical issues such as duty to inform, actionable results, and variants of unknown significance (VUS). Students are also asked to reflect on their feelings about getting genomic testing for themselves. An optional activity for advanced students (included in the teaching notes) involves using the Gene database at NCBI to explore variants of the CYP2C9 gene. The case study is appropriate for use in undergraduate genetics or molecular biology classrooms.

In the largest study of its kind, a research team has meshed extensive genome data on more than 50,000 people with their electronic health records and identified potential new disease-causing genes. The data further suggest that about one in 250 people may harbor a gene variant that puts them at risk for heart attacks and strokes, yet aren't receiving adequate treatment.

The 1000 Genomes Project is an international collaboration to produce an extensive public catalog of human genetic variation, including SNPs and structural variants, and their haplotype contexts. This resource will support genome-wide association studies and other medical research studies. The genomes of about 2500 unidentified people from about 25 populations around the world will be sequenced using next-generation sequencing technologies. The results of the study will be freely and publicly accessible to researchers worldwide. Further information about the project is available in the About tab. Information about downloading, browsing or using the 1000 Genomes data is available in the Data tab.

Current CRISPR-based screens often mutate the beginning of a gene, which sometimes results in the expression of a functional protein variant. To circumvent this problem, researchers at Cold Spring Harbor Laboratory (CSHL) designed CRISPR guide RNAs that would mutate the portion of a gene encoding a domain on the surface of the protein where a small molecule could bind to alter the protein's function. The team had previously identified such a binding pocket on the protein BRD4, and a small molecule inhibitor that binds in the pocket is an effective leukemia treatment.

What if sideline rage could be nipped in the bud with a quick genetic test that told Mom and Dad what sports - if any - Junior could master? The Boulder, Colo., company Atlas Sports Genetics today began selling just that sort of product: for $149, it says it will screen for variants of the gene ACTN3

A powerful tool called pVAAST that combines linkage analysis with case control association has been developed to help researchers and clinicians identify disease-causing mutations in families faster and more precisely than ever before. The researchers describe cases in which pVAAST (the pedigree Variant Annotation, Analysis and Search Tool) identified mutations in two families with separate diseases and a de novo or new variation in a 12-year-old who was the only one in his family to suffer from a mysterious and life threatening intestinal problem.

In the animal kingdom, humans are known for our big brains. But not all brains are created equal, and now we have new clues as to why that is. Researchers have uncovered eight genetic variations that help determine the size of key brain regions. These variants may represent "the genetic essence of humanity," says Stephan Sanders, a geneticist and pediatrician at the University of California, San Francisco, who was not involved in the study. These results are among the first to come out of the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) collaboration, involving some 300 scientists from 33 countries. They contributed MRI scans of more than 30,000 people, along with genetic and other information, most of which had been collected for other reasons. "This paper represents a herculean effort," Sanders says.

This directed case study follows the story of "Pauline," a 20-year-old college student who has just received results from a personal genetic testing kit she purchased online. The report shows a negative result for variants of the BRCA 1 and 2 genes, which are associated with a greater risk for breast cancer. Although Pauline has a family history of breast cancer, she concludes that she no longer needs to be concerned, or does she? As students work through the questions in this case study, they review the role of genes and how they code for proteins as well as the effects of proteins on health, especially on cellular growth regulation and cancer. They also learn about the process of genetic testing and consider the ramifications of positive and negative tests for diseases or health conditions, especially with respect to breast cancer. The case is designed for non-science majors in a scientific methods course and could also be used in an introductory biology course. The questions in the case could be adapted for an upper level genetics class.

This case study presents the mock trial of "Martin Miller." There is no question that Martin killed his girlfriend; he admitted to stabbing her in a violent rage. But what is the degree of his responsibility? By virtue of Martin having the MAOA-L gene variant, together with a history of childhood abuse, should his punishment be reduced? This hypothetical case, which requires students to think through the issues rather than simply look up a verdict, is based on actual events and violent behaviors that resulted in criminal charges claimed to be related to MAOA. The MAOA gene and its effect on behavior have been extensively studied, and research results have been introduced as evidence in court cases with differing results. The present case study allows students to explore how behavioral genetic information can be applied to a courtroom situation, and requires them to integrate information from biology, ethics, and the law. Note: Due to the unusual structure of the case, no answer key is available.

The Hardy-Weinberg equation is a relatively simple mathematical equation that describes a very important principle of population genetics: the amount of genetic variation in a population will remain the same from generation to generation unless there are factors driving the frequencies of certain alleles (genetic variants) to change.

This clicker case study follows a dialogue between two college students, Lucy and Dan, as they discover how alternative splicing of mRNA molecules can allow a single gene to code for multiple proteins. Dan is participating in a clinical trial for a drug that may treat his migraines by inhibiting calcitonin gene-related peptide, and Lucy is working in a summer research lab that studies the protein calcitonin. They soon realize that the two proteins are both encoded by the same gene, and through their questioning and dialogue they come to understand the phenomenon of alternative splicing. They also learn about other steps of mRNA processing and about monoclonal antibodies. This case was designed to be taught in a flipped classroom, but could easily be adapted for a more traditional classroom setting if content covered in the pre-class videos is covered during the case study instead. It was designed for an introductory-level molecular biology course, but could be adapted for higher levels by including more information about the physiology and regulatory mechanisms involved.