GENETICS OF ALCOHOL SENSITIVITY

在人体肝脏中，乙醇被二聚醇脱氢酶降解。 (ADH)转化为乙醛(ACh)，然后用四聚醛脱氢酶 (ALDH)，然后生产醋酸盐，最后是CO 2和H20。 ADH和ALDH基因座的遗传多态被怀疑为 在确定对乙醇的敏感程度方面具有重要意义。因此，要 了解酒精敏感和酒精中毒的遗传学，这是 重要的是评估ADH和ALDH基因的分子结构。AS 朝着这一目标迈出的第一步，我们计划描述不同的ADH 分子水平上的基因。 到目前为止，ADH基因的分子特征主要是在 只有ADH2基因座的基因组结构已经被 已澄清。作为了解人类基因组遗传学的第一步 对于酒精敏感性，我们建议对所有ADH基因进行特征分析，包括 不仅在第I类的ADH1、ADH2和ADH3基因座上，而且在那些 第二类和第三类基因座。使用PI的DNA，我们已经分离出 部分基因组克隆不仅包括所有这些ADH基因，还包括一种新的 此前未知的ADH基因。为了描述所有的 这些ADH基因，我们建议用这些基因构建一个文库。 同样的基因组DNA，进行筛选，并进行DNA测序。 通过使用获得的DNA序列数据，我们计划研究DNA多态 聚合酶链法检测ADH各基因座的信息区 反应和直接基因组测序。这些数据和其他已发布的数据 也将用于研究ADH基因分化的模式。

In the human liver, ethanol is degraded by dimeric alcohol dehydrogenase (ADH) to acetaldehyde (AcH) and then by tetrameric aldehyde dehydrogenase (ALDH) with the subsequent production of acetate, and finally Co 2 and H20. The genetic polymorphisms at the ADH and ALDH loci are suspected to have importance in determining the degree of susceptibility to ethanol. Thus, to understand the genetics of alcohol sensitivity and alcoholism, it is important to evaluate the molecular structure of the ADH and ALDH genes. As an initial step toward that end, we plan to characterize different ADH genes at the molecular level. So far, molecular characterization of the ADH genes has been mostly at the cDNA level and only the genomic structure of the ADH2 locus has been elucidated. As an initial step toward the understanding of the genetics of alcohol sensitivity, we propose to characterize all ADH genes, including not only those at the ADH1, ADH2, and ADH3 loci of class I but also those of the class II and III loci. Using DNA from the PI, we have isolated partial genomic clones not only of all these ADH genes but also of a new ADH gene which was previously unknown. In order to characterize all of these ADH genes completely, we propose to construct a library using the same genomic DNA, screen it, and perform DNA sequencing. By using the DNA sequence data obtained, we plan to study DNA polymorphism at informative regions at each ADH locus by the method of polymerase chain reaction and direct genomic sequencing. These data and other published data will also be used to study the pattern of ADH gene differentiation.