GENETICS OF THYROID HORMONES IN MEXICAN AMERICANS

墨西哥裔美国人的甲状腺激素遗传学

• 批准号: 2905762
• 负责人: PAUL B SAMOLLOW
• 金额: $ 18.66万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-15 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2905762
• 关键词: Mexican Americans; blood chemistry; family genetics; genetic markers; genetic polymorphism; genotype; human genetic material tag; human population genetics; human tissue; linkage mapping; nucleic acid repetitive sequence; phenotype; polymerase chain reaction; quantitative trait loci; radioimmunoassay; statistics /biometry; thyroglobulin; thyroid hormones; thyrotropin; thyroxine; triiodothyronine

DESCRIPTION: (Adapted from Investigator's Abstract) Thyroid hormones play major roles in the regulation of protein synthesis, basal metabolism, and lipolysis and lipogenesis. These wide ranging actions suggest that thyroid hormone variation may be intimately connected with variation in health related characteristics such as fat distribution, bone metabolism, and lipoprotein metabolism. Because these variables are risk factors in many common diseases such as atherosclerosis, diabetes, and osteoporosis, information on the genetic component of variation in thyroid hormone levels is a crucial factor in understanding the genetic basis of common disease susceptibility. A multidisciplinary investigation coupling molecular genetic methods and statistical genetic approaches will be conducted to examine the genetic components of variation in thyroid hormone phenotypes in a set of Mexican American families that is currently under investigation with regard to genetic factors in susceptibility to atherosclerosis, diabetes, osteoporosis, and obesity. The overall objectives are to detect genetic effects on normal thyroid hormone variation and to localize and identify them by statistical genetic analyses of pedigree data. The specific aims are to: 1) measure serum concentrations of nine thyroid hormone phenotypes; 2) evaluate each individual's genotype at 24 polymorphic candidate loci; 3) detect evidence of linkage between quantitative trait loci (QTLs) for thyroid hormone phenotypes and approximately 325 polymorphic short tandem repeat (STR) markers via initial genome-wide screening using two-point variance component analysis; and 4) refine preliminary evidence of linkage of candidate genes and selected STR loci (determined via Aim 3) with thyroid hormone QTLs by performing more powerful multipoint variance component and penetrance-based quantitative trait linkage analyses. DNA samples from 1,000 individuals from 24 families will be analyzed by polymerase chain reaction (PCR) based approaches and blot hybridization methods to determine genotypes at the 24 candidate loci. Genotypes at the 325 STR loci will be obtained from another research project currently underway. Concentrations of nine serum thyroid hormones from the same 1,000 individuals will be assessed by radioimmunometric methods. QTL linkage analyses will be performed to test for linkage between genes that influence thyroid hormone variation and the two sets of genetic markers, i.e., candidate genes and STR markers.

描述：（改编自研究者摘要）甲状腺激素的作用 在调节蛋白质合成、基础代谢和 脂肪分解和脂肪生成。 这些广泛的作用表明，甲状腺 激素变化可能与健康变化密切相关 相关特征，如脂肪分布、骨代谢，以及 脂蛋白代谢 因为这些变量是许多风险因素， 常见疾病如动脉粥样硬化、糖尿病和骨质疏松症， 关于甲状腺激素水平变异的遗传因素的资料 是理解常见疾病遗传基础的关键因素 易感性 一个多学科的研究耦合分子遗传学方法和 统计遗传学方法将进行检查的遗传 一组墨西哥人甲状腺激素表型变异的组成部分 目前正在接受调查的美国家庭 动脉粥样硬化，糖尿病， 骨质疏松症和肥胖症。 总体目标是检测遗传 对正常甲状腺激素变化的影响，并定位和识别 通过对系谱数据的统计遗传分析， 具体目标 是：1）测量九种甲状腺激素表型的血清浓度; 2)在24个多态性候选位点上评估每个个体的基因型; 3） 检测数量性状基因座（QTL）之间的连锁证据， 甲状腺激素表型和大约325个多态性短串联 重复（STR）标记，通过使用两点法的初始全基因组筛选 方差成分分析; 4）完善联系的初步证据 候选基因和选定的STR基因座（通过Aim 3确定）与甲状腺 激素QTL进行更强大的多点方差分量， 基于遗传距离的数量性状连锁分析 来自24个家庭的1,000名个体的DNA样本将被分析， 基于聚合酶链反应（PCR）的方法和印迹杂交 确定24个候选基因座基因型的方法。 基因型 325个STR基因座将从另一个研究项目中获得， 正在进行中 来自同一1000人的9种血清甲状腺激素浓度 将通过放射免疫测定法对个体进行评估。 QTL连锁 将进行分析，以测试基因之间的联系，影响 甲状腺激素变异和两组遗传标记，即， 候选基因和STR标记。