GENE MAPPING AND LINKAGE STUDIES WITH SHORT TANDEM REPEAT (STR) MARKERS

短串联重复 (STR) 标记的基因作图和连锁研究

• 批准号: 2565415
• 负责人: J LONG
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2565415
• 关键词: Native Americans; Scandinavian; alcohol dehydrogenase; alcoholism /alcohol abuse; antisocial personality; behavioral genetics; clinical research; disease /disorder proneness /risk; enzyme activity; genetic markers; genetic polymorphism; genotype; human genetic material tag; human subject; linkage mapping; nucleic acid repetitive sequence; sex chromosomes

We are searching for genetic linkage between genes that contribute to the predisposition to alcoholism and related behaviors using over 400 highly polymorphic DNA marker loci that span the human genome. To date, we have completed over 150,000 locus typings, primarily on American Indians and Finns. One finding concerns a dinucleotide repeat polymorphism in the D2 dopamine receptor gene on chromosome 12. In 459 Southwestern Indians, concordant unaffected sibpairs share identical by descent marker alleles more frequently than expected (P<0.008). Despite this evidence for linkage, the alleles at this locus are not significantly associated with alcoholism. This implies that the effect is due to a closely linked gene. We have also looked for genetic linkage between alcoholism and typings at 463 autosomal microsatellite using 125 of the Southwestern Indian subjects. The typings were conducted as a part of an NIDDK collaborative study on diabetes. These analyses revealed 22 loci with p<5% and 7 loci p<1%. Interestingly, 3 chromosome 4 loci that map along with the alcohol dehydrogenase gene cluster (ADH), have p-values below 1%. There are well known alleles in the ADH gene family that enhance catalytic activity. Since high ADH activity lowers tolerance to alcohol, carriers of these alleles are less likely to be alcoholic. Thus, variants at ADH exert a protective effect, where they influence alcoholism vulnerability. Populations, such as this Southwestern Indian tribe, with a high prevalence of alcoholism may reveal other protective factors. We are now investigating Y chromosome DNA variability a sample of 270 Finns. Variability in the TPQ personality scale were investigated along with alcohol dependence and antisocial personality disorder (ASPD). Reward dependence was associated with 5 related Y chromosome types (p<0.05) that are relatively common. With regard to alcohol dependence and ASPD, we find a significant association between 3 groups of Y chromosomes and alcoholism (P< 0.02, P<0.001, P<0.04). There were no discernible Y chromosome effects on ASPD.

我们正在寻找有助于的基因之间的遗传联系 对酒精中毒和相关行为的易感性超过400个 跨越人类基因组的多态性DNA标记基因座。迄今为止，我们有 完成了150,000多个基因座键入，主要是在美国印第安人和 芬恩。一个发现涉及D2中的二核苷酸重复多态性 12染色体上的多巴胺受体基因。在459个西南印第安人中， 一致的不受影响的sibpairs通过下降标记等位基因共享相同 比预期的要多（p <0.008）。尽管有证据表明 链接，该基因座的等位基因与 酗酒。 这意味着效果是由于紧密链接 基因。我们还寻找酒精中毒与 使用125个西南部的463个常染色体微卫星的打字 印度主题。打字是作为NIDDK的一部分进行的 关于糖尿病的协作研究。这些分析揭示了22个基因座 P <5％和7个基因座P <1％。 有趣的是，3染色体4位基因座 与酒精脱氢酶基因簇（ADH）一起，p值以下 1％。 ADH基因家族中有众所周知的等位基因增强 催化活性。 由于高ADH活性降低了对酒精的耐受性，因此 这些等位基因的载体不太可能是酗酒的。 因此， ADH的变体具有保护作用，它们会影响它们 酒精中毒脆弱性。 人口，例如西南印度人 部落，酗酒率很高，可能会揭示其他保护性 因素。 我们现在正在研究Y染色体DNA变异性A样品 270名芬兰人。 研究了TPQ人格量表的变异性 以及酒精依赖和反社会人格障碍（ASPD）。 奖励依赖性与5种相关Y染色体类型有关 （p <0.05）相对常见。 关于酒精依赖 和ASPD，我们发现3组Y之间存在显着关联 染色体和酒精中毒（p <0.02，p <0.001，p <0.04）。没有 可识别的Y染色体对ASPD的影响。