A number of candidate gene polymorphisms have been shown to be associated with macrovascular disease risk factors in non-diabetic populations, however, the genetic contribution to vascular disease in diabetic patients has been less well studied. The program project will examine whether strategically selected candidate genes can be implicated in the development of macro- and micro-vascular disease complications in the DCCT/EDIC cohort of Type 1 diabetes patients and the VA Cooperative Trial of Type 2 Diabetes patients. Investigators will examine whether these polymorphisms are associated with quantitative and qualitative measures of vascular disease and/or with molecular biomarkers measured within the program project that represent proteins or protein activities encoded by these genes. The overall goal of the Molecular and Statistical Genetics Core is to facilitate studies assessing whether specific candidate gene polymorphisms are associated with the development of macrovascular and microvascular disease complications in diabetes. The Core?s specific aims I include: (1) make available technologies for DNA sequencing, genotyping, and polymorphism/mutation detection to the project investigators; (2) help project investigators in study design, statistical analysis, and power calculations for studying the genetic basis of vascular complications in diabetes. The core will provide the following services: (I) procurement, purification, and banking of DNA; (ii) rapid turnaround DAN sequencing; (iii) rapid and high throughput characterization of gene polymorphism/mutations in candidates selected by the various project investigators; (iv) screening of gene candidates for novel polymorphisms/mutations; (v) identification and use of single nucleotide polymorphisms (SNPs) as well as microsatellite markers for mapping chromosomal loci; (vi) statistical genetic analysis including power calculations, experiment planning, association analysis, haplotype analysis, analyses for publications, and segregation and linkage analyses is needed.
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