Genetic testing for risk of inherited breast and ovarian cancers: Payment issues following the 2013 Myriad Supreme Court Case

This is an undergraduate senior thesis submitted in 2014 by Annie Niehaus, a student at Pomona College, in partial fulfillment of the requirements for the degree of Bachelor of Arts in Public Policy Analysis - Chemistry. This work was advised by Robert Cook-Deegan at Duke University. It was funded in part by the Institute for Genome Sciences & Policy summer undergraduate research fellowship and by the National Human Genome Research Institute through grant P50 HG003391

A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation

Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research

Addressing the Need for Depression Inventories in American Sign Language

Using state-of-the-art techniques, the authors interpreted two commonly used depression inventories, the revised Beck Depression Inventory (BDI-II) and Patient Health Questionnaire–9 (PHQ-9), into American Sign Language (ASL): BDI-II-ASL and PHQ-9-ASL, respectively. A national sample of 361 deaf individuals who preferentially use ASL completed the BDI-II-ASL and PHQ-9-ASL online. BDI-II-ASL and PHQ-9-ASL scores were significantly and positively correlated. The results showed no significant differences in scores due to gender, Deaf cultural identification, race, ethnicity, or employment status. However, the results did show that less education was significantly associated with higher depression scores. The BDI-II-ASL and PHQ-9-ASL require norming in a comparative study of a confirmed diagnostic group and healthy control group

Points to consider for sharing variant-level information from clinical genetic testing with ClinVar

Data sharing between laboratories, clinicians, researchers, and patients is essential for improvements and standardization in genomic medicine; encouraging genomic data sharing (GDS) is a key activity of the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen). The ClinGen initiative is dedicated to evaluating the clinical relevance of genes and variants for use in precision medicine and research. Currently, data originating from each of the aforementioned stakeholder groups is represented in ClinVar, a publicly available repository of genomic variation, and its relationship to human health hosted by the National Center for Biotechnology Information at the NIH. Although policies such as the 2014 NIH GDS policy are clear regarding the mandate for informed consent for broad data sharing from research participants, no clear guidance exists on the level of consent appropriate for the sharing of information obtained through clinical testing to advance knowledge. ClinGen has collaborated with ClinVar and the National Human Genome Research Institute to develop points to consider for clinical laboratories on sharing de-identified variant-level data in light of both the NIH GDS policy and the recent updates to the Common Rule. We propose specific data elements from interpreted genomic variants that are appropriate for submission to ClinVar when direct patient consent was not sought and describe situations in which obtaining informed consent is recommended

Gapless genome assembly of Colletotrichum higginsianum reveals chromosome structure and association of transposable elements with secondary metabolite gene clusters

Background: The ascomycete fungus Colletotrichum higginsianum causes anthracnose disease of brassica crops and the model plant Arabidopsis thaliana. Previous versions of the genome sequence were highly fragmented, causing errors in the prediction of protein-coding genes and preventing the analysis of repetitive sequences and genome architecture. Results: Here, we re-sequenced the genome using single-molecule real-time (SMRT) sequencing technology and, in combination with optical map data, this provided a gapless assembly of all twelve chromosomes except for the ribosomal DNA repeat cluster on chromosome 7. The more accurate gene annotation made possible by this new assembly revealed a large repertoire of secondary metabolism (SM) key genes (89) and putative biosynthetic pathways (77 SM gene clusters). The two mini-chromosomes differed from the ten core chromosomes in being repeat-and AT-rich and gene-poor but were significantly enriched with genes encoding putative secreted effector proteins. Transposable elements (TEs) were found to occupy 7% of the genome by length. Certain TE families showed a statistically significant association with effector genes and SM cluster genes and were transcriptionally active at particular stages of fungal development. All 24 subtelomeres were found to contain one of three highly-conserved repeat elements which, by providing sites for homologous recombination, were probably instrumental in four segmental duplications. Conclusion: The gapless genome of C. higginsianum provides access to repeat-rich regions that were previously poorly assembled, notably the mini-chromosomes and subtelomeres, and allowed prediction of the complete SM gene repertoire. It also provides insights into the potential role of TEs in gene and genome evolution and host adaptation in this asexual pathogen