The international 1q type 2 diabetes consortium

国际1q 2型糖尿病联盟

• 批准号: 7575177
• 负责人: Mark Ian McCarthy
• 金额: $ 104.97万
• 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/7575177
• 关键词: 1q21; Adopted; African; Ally; Asia; Asians; Bioinformatics; Biological; Boxing; Chromosome Mapping; Chromosomes; Classification; Clinical; Clinical Management; Credentialing; DNA; DNA Resequencing; Data; Data Analyses; Development; Diabetes Mellitus; Diagnostic; Disease; Ensure; Epidemiology; 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; 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.

本申请研究的目的是确定糖尿病易感基因， 染色体1 q。染色体1 q21 -25的25 Mb区域已经被靶向，因为它含有一个非常大的 一个复制良好的2型糖尿病连锁信号，现在在一系列人群中进行的扫描中检测到 包括欧洲人、东亚人、美洲土著人和非洲裔美国人。假设是 这种复制的连锁反应反映了一个或多个易感基因的作用， 影响多种族人群中2型糖尿病的遗传易感性。该战略 采用结合系统，高密度连锁不平衡作图与详尽的检查， 选择职位候选人。该提案来自一个独特的国际联盟， 基础研究者代表了具有最强证据表明1 q与以下专业知识相关的人群： 来自国际人类基因组单体型图领导小组的高通量基因组学、信息学和统计学 项目因此，该联盟在应用基因分型的最新发展方面处于有利地位 技术，信息学和人类序列变异的理解分析无与伦比的 临床资源。对4000多个样本的3000个1 q SNP的初步数据进行分析， 发现了几个与糖尿病相关的基因。我们的具体目标是： 1.通过最后一次基因测序，完成整个1 q感兴趣区域的间接连锁不平衡调查。 一轮基因分型，旨在确保全面捕获常见变异的影响; 2.通过进一步的SNP和更大的临床样本分析来跟踪检测到的关联信号; 3.通过开发专用的 信息学工具，并使用这些工具，使生物学候选人的系统评价 区域转录本，并支持多态重复的搜索; 4.对如此鉴定的基因进行直接、全面的分析，以表征病因学变体。 识别负责连锁信号的特定变体将增强我们对以下方面的理解： 2型糖尿病的发生发展中的基本分子事件。这些信息将 有助于未来的诊断和治疗进展，在这种情况下的临床管理。