Long J C, Knowler W C, Hanson R L, Robin R W, Urbanek M, Moore E, Bennett P H, Goldman D
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8110, USA. jeff
Am J Med Genet. 1998 May 8;81(3):216-21. doi: 10.1002/(sici)1096-8628(19980508)81:3<216::aid-ajmg2>3.0.co;2-u.
To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a 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 using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis.
为了确定影响易感性或抗性的特定基因，我们在美国西南部一个印第安部落中进行了全常染色体基因组扫描，以寻找与酒精依赖的遗传连锁关系。对于属于扩展家系的152名受试者，可获得517个常染色体微卫星位点的基因型和临床评估结果，这些受试者构成了172个同胞对。使用两点和多点同胞对回归方法，在两个基因组区域出现了高度提示性的连锁证据；这两个区域都含有神经遗传学候选基因。在11号染色体p臂上的D11S1984位点（名义P = 0.00007，对数似然比约等于3.1）观察到了最强的证据，该位点紧邻DRD4多巴胺受体和酪氨酸羟化酶（TH）基因。在4号染色体p臂上靠近β1 GABA受体基因的D4S3242位点（名义P = 0.0002，对数似然比约等于2.8）观察到了较好的证据。有趣的是，4号染色体q臂上酒精脱氢酶基因簇中的三个位点在两点分析中有连锁证据，但在多点分析中没有。
