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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK063491-11
Application #
8443928
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O2))
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
11
Fiscal Year
2013
Total Cost
$263,327
Indirect Cost
$13,750
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Keaton, Jacob M; Hellwege, Jacklyn N; Ng, Maggie C Y et al. (2016) GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR TYPE 2 DIABETES IN AFRICAN AMERICANS. Pac Symp Biocomput 22:242-253
Below, Jennifer E; Parra, Esteban J; Gamazon, Eric R et al. (2016) Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs. Sci Rep 6:19429
Chung, Heekyung; Chou, Winjet; Sears, Dorothy D et al. (2016) Time-restricted feeding improves insulin resistance and hepatic steatosis in a mouse model of postmenopausal obesity. Metabolism 65:1743-1754
Wang, Shuai; Zhao, Jing Hua; An, Ping et al. (2016) General Framework for Meta-Analysis of Haplotype Association Tests. Genet Epidemiol 40:244-52
Golden, Diana; Kolmakova, Antonina; Sura, Sunitha et al. (2016) Lymphocyte activation gene 3 and coronary artery disease. JCI Insight 1:e88628
Gholkar, Ankur A; Senese, Silvia; Lo, Yu-Chen et al. (2016) The X-Linked-Intellectual-Disability-Associated Ubiquitin Ligase Mid2 Interacts with Astrin and Regulates Astrin Levels to Promote Cell Division. Cell Rep 14:180-8
Larson, Nicholas B; Decker, Paul A; Wassel, Christina L et al. (2016) Blood group antigen loci demonstrate multivariate genetic associations with circulating cellular adhesion protein levels in the Multi-Ethnic Study of Atherosclerosis. Hum Genet 135:415-23
Tian, Xiao Yu; Ganeshan, Kirthana; Hong, Cynthia et al. (2016) Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance. Cell Metab 23:165-78
(2016) A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape. Nat Commun 7:13357
Sajuthi, Satria P; Sharma, Neeraj K; Chou, Jeff W et al. (2016) Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity. Hum Genet 135:869-80

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