The international 1q type 2 diabetes consortium

国际1q 2型糖尿病联盟

• 批准号: 7373650
• 负责人: Mark Ian McCarthy
• 金额: $ 101.62万
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7373650
• 关键词: 1q21; Adopted; African; Ally; Asia; Asians; Bioinformatics; Biological; Boxing; Chromosome Mapping; Chromosomes; Classification; Clinical; Clinical Management; Condition; Credentialing; DNA; DNA Resequencing; Data; Data Analyses; Development; Diabetes Mellitus; Diagnostic; Disease; Ensure; Ethnic group; Europe; European; Evaluation; Event; Figs - dietary; Funding; Future; Genes; Genetic Predisposition to Disease; Genome Scan; Genomics; Genotype; Human; Individual; Informatics; International; Knowledge; Link; Linkage Disequilibrium; Linkage Disequilibrium Mapping; Molecular; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; North America; Output; Population; Positioning Attribute; Predisposition; Range; Research; Research Personnel; Resources; Sampling; Scanning; Sequence Analysis; Signal Transduction; Surveys; Susceptibility Gene; Testing; Therapeutic; Time; Transcript; Variant; Work; attenuation; base; conditioning; data integration; density; design; follow-up; genotyping technology; improved; interest; member; multidisciplinary; programs; statistics; tool

The objective of the research in this application is to identify diabetes-susceptibility genes mapping to chromosome 1q. A 25Mb region of chromosome 1q21-25 has been targeted since it contains an extremely well-replicated type 2 diabetes linkage signal, now detected in scans performedin a range of populations including those of European, East Asian, Native Americanand African Americanorigin. The hypothesis to be tested is that this replicated linkage reflectsthe action of one or more susceptibility genes capable of influencing the inherited predisposition to type 2 diabetes in multiple ethnic groups. The strategy to be adopted combines systematic, high-density linkage disequilibrium mapping with exhaustive examination of selected positional candidates. The proposal comesfrom a unique international consortium that allies clinical and basic investigators representing populations with the strongest evidence for 1q linkage with expertise in high-throughput genomics, informatics and statistics from leading groups in the International HapMap project. This consortium is therefore powerfully-placed to apply the latest developments in genotyping technology, informatics and the understanding of human sequence variation to analysis of unparalleled clinical resources. Analysis of preliminary data from 3000 1q SNPs typed for over 4000 samples has already identified several genes showing replicated associations with diabetes. Our specific aims are: 1. to complete the indirect linkage disequilbrium survey of the entire 1q region of interest through a final round of genotyping designed to ensure comprehensive capture of the effects of common variation; 2. to follow up the association signals detected through analysis of further SNPs and larger clinical samples; 3. to integrate the association data obtained in its biological context through development of dedicated informatics tools, and to use these tools to enable a systematic evaluation of the biological candidacy of regional transcripts and to support a search for polymorphic duplications; 4. to undertake direct, comprehensive analysis of the genes so identified to characterize etiological variants. Identification of the specific variant(s) responsible for the linkage signal will enhance our understanding of the fundamental molecular events involved in the development of type 2 diabetes. This information will contribute to future diagnostic and therapeutic advances in the clinical management of this condition.

本研究的目的是确定糖尿病易感基因的定位