Genetic susceptibility contributes significantly to the development of diabetes, and to othei"""""""" metabolic and endocrine disorders associated with diabetes and their complications. Recent successes in genome wide association and exome sequencing have demonstrated that the technological capability now exists to identify many ofthe genes responsible for complex disorders. To be successful in such endeavors, it is necessary to combine expertise in genetic epidemiology, clinical investigation, molecular genotyping, DNA sequencing, and mathematical genetic analysis. The goal of the Human Genetics Core is to offer isuch expertise to DRC investigators conducting studies into the genetics of diabetes, its complications and related endocrine disorders. To achieve this objective, the Human Genetics Core will: 1) assist DRC investigators with initial study design, bioinformatic, data analysis, and data interpretation support;2) establish and maintain EBV transformed lymphoblastoid cell lines and generate nonviable cell pellets for DNA/RNA isolation;3) provide anonymized lymphoblastoid cell lines from subjects well characterized for diabetes and/or insulin sensitivity to DRC investigators for such purposes as searching for variations in specific candidate genes and evaluating differential expression of candidate genes as a function of insulin resistance;4) provide access to molecular methodology for candidate gene and genome wide and specialized high throughput SNP testing, and candidate gene, exome and whole genome sequencing;5) make induced pluripotent stem cells (iPSCs) available to investigators as a means of investigating the impact of specific genetic variants on organ development and tissue function;and 6) provide training to DRC investigators and staff so they can perform many of these procedures themselves, with consultative support from Core staff. In the last cycle, the Human Genetics Core brought GWAS technology to DRC investigators and in this cycle extends the technology available for studying human samples with the addition of specialized genotyping chips, methylation chips, exome sequencing, and iPSC technology. The DRC offers a unique opportunity to facilitate research directed at identifying and characterizing the genes responsible for Type 2 diabetes and related disorders, including both macrovascular and microvascular complications, by providing access to both the expertise and facilities necessary for such genetic research in human populations.
In order to reduce the prevalence and severity of diabetes and its complications, a comprehensive understanding ofthe pathophysiology of diabetes and related disorders is required. By aiding investigators in the identification of the genes and genetic variants that influence diabetes risk, the Human Genetics Core will be helping to achieve the goal of reducing the burden of this disease.
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