Diabetes Genome Anatomy Project |
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Projects > Project 5B
Project 5B:
Genetics of Adipose-Regulated Genes in
Insulin-Resistance and Type 2 Diabetes
Primary Investigator: Alessandro Doria, M.D., Ph.D. (Joslin Diabetes Center)
Specific Aims
- To complement the linkage disequilibrium data provided by the HapMap project with additional single nucleotide polymorphisms (SNPs), in order to select variants that comprehensively capture genetic variability at the loci identified by DGAP as possible type 2 diabetes genes.
- To investigate through these SNPs whether genetic variability in these candidate genes is associated with the development of insulin-resistance and type 2 diabetes in population studies.
Identification of polymorphisms affecting insulin-sensitivity and the risk of type 2 diabetes will point to specific pathways mediating the development of these disorders. This knowledge may suggest novel strategies for developing pharmacological or lifestyle interventions for preventing type 2 diabetes. Furthermore, identification of these genetic markers would allow the identification of individuals at high risk of diabetes, so that preventive programs could be specifically targeted at these subjects early in life.
Summary
The Diabetes Genome Anatomy Project (DGAP) is using expression profiling to identify genes with putative roles in insulin action and the pathophysiology of diabetes. Genetic variability at these loci may play a causal role in the development of insulin-resistance and type 2 diabetes. One powerful way to test such hypothesis is to study whether inherited sequence differences are associated with diabetes in human populations. With the advent of the human genome sequence, improved understanding of genetic variation, and high-throughput technologies it is now possible to comprehensively test allelic variation at candidate loci. In this project, we propose to generate data on the association between polymorphisms and type 2 diabetes or other metabolic traits for a carefully selected set of 100 genes that are identified by the DGAP as being highly adipose-regulated, insulin-regulated, and/or abnormally expressed in type 2 diabetes. Since molecules secreted by the adipose tissue are emerging as major modulators of insulin-sensitivity and the risk of type 2 diabetes, special emphasis is placed on genes that reside in the cellular pathways regulating the release of adipokines and FFA from adipocytes or their action on peripheral tissues.