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: 6160328
• 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/6160328
• 关键词: Native Americans; Scandinavian; alcohol dehydrogenase; alcoholism /alcohol abuse; antisocial personality; behavioral /social science research tag; 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 500 highly polymorphic DNA marker loci that span the human genome. To date, we have completed over 200,000 locus typings, primarily on Southwestern American Indians and Finns. We have performed a whole autosomal genome scan for genetic linkage to alcohol dependence in the Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions; both regions harbor neurogenetic candidate genes. The best evidence is seen with D11S1984 on chromosome 11p, in close proximity to the DRD4 dopamine receptor gene. Good evidence is seen with D4S3242 on chromosome 4p, nearby the beta1 GABA receptor gene. In Finns, we have investigated autosomal and Y chromosome DNA variability in relation to the Tridimensional Personality Questionnaire (TPQ) and alcohol dependence and antisocial personality disorder (ASPD). For the autosomal genes, we find evidence for genetic linkage and association between ASPD with alcoholism and the chromosome 6 marker locus D6S286. We also find evidence for linkage and association between ASPD with alcoholism and a polymorphism in the closely linked serotoinin receptor gene HTR1B. With regard to the Y chromosome, we find a significant association with alcohol dependence or abuse and three groups of Y chromosomes that are closely related by their mutational histories.

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500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200,000多个基因座键入，主要是在美国西南部 印第安人和芬兰人。 我们已经进行了整个常染色体基因组扫描 西南美洲印第安人的遗传与酒精依赖关系 部落。 517常染色体微卫星基因座和临床的基因型 评估可用于属于扩展的152名受试者 血统和形成172个同胞。 强烈暗示的证据 链接出现在两个基因组区域；两个区域都有神经源 候选基因。 最好的证据是染色体上的D11S1984 11p，靠近DRD4多巴胺受体基因。 好的 在4p染色体上使用D4S3242看到证据，附近是Beta1 Gaba 受体基因。 在芬兰人中，我们已经研究了常染色体和Y染色体 与三维性格有关的DNA变异性 问卷（TPQ）和酒精依赖和反社会个性 疾病（ASPD）。 对于常染色体基因，我们找到了遗传的证据 ASPD与酒精中毒与染色体之间的联系和关联 6标记基因座D6S286。 我们还找到了联系和关联的证据 在ASPD之间与酒精中毒和紧密联系的多态性 5-羟色胺受体基因Htr1b。 关于Y染色体，我们发现 与酒精依赖或滥用的重要关联，三个 Y染色体的组与它们的突变密切相关 历史。