GENETICS OF THYROID HORMONES IN MEXICAN AMERICANS

描述：(改编自《调查者摘要》)甲状腺激素发挥作用 在调节蛋白质合成、基础代谢和 脂肪分解和脂肪生成。这些广泛的行为表明，甲状腺 激素的变化可能与健康的变化密切相关 相关特征，如脂肪分布、骨代谢和 脂蛋白代谢。因为这些变量在许多情况下都是风险因素 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成分的信息 是理解常见疾病的遗传基础的关键因素 敏感度。 分子遗传学和分子遗传学相结合的多学科研究 将采用统计遗传方法来检查基因 一组墨西哥人甲状腺激素表型变异的成分 目前正在接受调查的美国家庭 易患动脉粥样硬化、糖尿病、 骨质疏松症和肥胖。总体目标是检测基因 对正常甲状腺激素变化的影响及定位鉴定 对家系资料进行统计遗传分析。具体目标 1)测定9种甲状腺激素表型的血清浓度； 2)在24个候选多态基因座上评估每个个体的基因型；3) 检测数量性状基因座(QTL)之间存在连锁的证据 甲状腺激素表型和大约325个多态短串联 重复(STR)标记通过使用两点的全基因组初始筛查 方差成分分析；以及4)提炼连锁的初步证据 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通过执行更强大的多点方差分量和 基于外显度的数量性状连锁分析。 来自24个家庭的1000个人的DNA样本将通过 聚合酶链式反应和斑点杂交技术 方法对24个候选基因座进行基因分型。基因分型 目前将从另一个研究项目获得325个STR基因座 正在进行中。同一1000人中9种血清甲状腺激素的浓度 个人将通过放射免疫方法进行评估。QTL连锁 将进行分析，以测试影响 甲状腺激素变异和两套遗传标记，即， 候选基因和STR标记。

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.