IDENTIFYING NIDDM GENES USING ADMIXED POPULATIONS

使用混合群体鉴定 NIDDM 基因

• 批准号: 2906211
• 负责人: Mark D Shriver
• 金额: $ 27.05万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2906211
• 关键词: diabetes mellitus genetics; glucose metabolism; human genetic material tag; human population genetics; human tissue; insulin; insulin receptor; noninsulin dependent diabetes mellitus; nucleic acid sequence; oligonucleotides; polymerase chain reaction; restriction fragment length polymorphism

DESCRIPTION: (Adapted from investigator's abstract) Several common chronic diseases demonstrate prevalence differences among ethnically classified groups For example, non-insulin dependent diabetes mellitus (NIDDM) is 2-fold to 10-fold more frequent in Hispanic and Amerindian populations than in European and European-American populations; hypertension is more common among African Americans; and obesity has a higher frequency in Hispanics and Amerindians. These diseases are difficult to study using family-based linkage techniques, primarily because of age-dependent onset and interactions between genes and environmental exposures. A new method for disease gene mapping using the linkage disequilibrium created when ethnically distinct populations hybridize is well suited to the study of common disease in hybrid populations like the U.S. African Americans and Hispanic Americans. When populations admix, allelic associations are formed at loci that have marked differences in allele frequency. The magnitude of this admixture linkage disequilibrium (ALD) is proportional to the allele frequency differential (delta) between the parental populations. Allelic associations between unlinked loci quickly decay in 3 to generations. Closely spaced loci, however, will remain in non-random association for many generations; the length of time and the magnitude of the linkage disequilibrium being dependent on the proximity of the loci and the delta levels between the parental populations. Using this approach, it will thus be possible to detect genetic linkage between polymorphic markers and disease susceptibility loci by way of associations observed in cases and controls. The investigators have performed extensive computer simulation studies on the dynamics of linkage disequilibrium in admixed populations. This work has shown that there will be significant statistical power to detect disease genes using mapping by ALD. This is especially true for testing the importance of candidate genes and candidate regions. They propose to test 40 candidate genes and regions for linkage to NIDDM in a well-characterized population of Hispanics living in the San Luis Valley of Colorado. They will verify any positive associations found using sib-pair linkage analysis and the transmission disequilibrium test.

描述：(改编自调查人员摘要)几种常见的慢性 疾病在种族分类中的患病率存在差异 例如，非胰岛素依赖型糖尿病(NIDDM)是 在西班牙裔和美洲印第安人中的发生率是 在欧洲和欧洲裔美国人中，高血压更为常见 在非裔美国人中；肥胖症在西班牙裔和 美洲印第安人。这些疾病很难使用以家庭为基础的方法进行研究 连锁技术，主要是因为年龄相关的发病和 基因与环境暴露之间的相互作用。一种新的检测方法 利用连锁不平衡进行疾病基因作图 不同种族的种群杂交非常适合于研究 杂交种人群中的常见疾病，如美国非裔美国人和 拉美裔美国人。当种群混合时，就形成了等位基因关联。 在等位基因频率上有显著差异的基因座。规模的大小 这种混合连锁不平衡(ALD)与等位基因成正比 亲本群体之间的频率差异(增量)。等位基因 未连锁的基因座之间的关联性在3代到几代之间迅速衰退。 然而，在许多情况下，紧密间隔的基因座将保持非随机关联 世代；时间的长短和联系的程度 不平衡取决于位置和三角洲的接近程度 亲代群体之间的水平。使用这种方法，它将因此 有可能检测到多态标记和 通过在病例和患者中观察到的关联来确定疾病易感基因 控制。调查人员进行了广泛的计算机模拟 混合群体中连锁不平衡的动态研究。 这项工作已经表明，将有显著的统计力量 利用ALD定位检测疾病基因。这一点对于 测试候选基因和候选区域的重要性。他们 建议测试40个与NIDDM连锁的候选基因和区域 生活在圣路易斯山谷的西班牙裔人口的特征 科罗拉多州。他们将验证使用Sib-Pair发现的任何积极关联 连锁分析和传动不平衡检验。