Human chromosomal localization of genes encoding the gamma 1 and gamma 2 subunits of the gamma-aminobutyric acid receptor indicates that members of this gene family are often clustered in the genome.
Human chromosomal localization of genes encoding the gamma 1 and gamma 2 subunits of the gamma-aminobutyric acid receptor indicates that members of this gene family are often clustered in the genome.
复制标题
编码γ-氨基丁酸受体的γ1和γ2亚基的基因的人类染色体定位表明该基因家族的成员通常聚集在基因组中。
DOI：
10.1073/pnas.89.13.5857
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发表时间：
1992
影响因子：
11.1
通讯作者：
Sikela,JM
中科院分区：
文献类型：
--
作者：
Wilcox,AS;Warrington,JA;Gardiner,K;Berger,R;Whiting,P;Altherr,MR;Wasmuth,JJ;Patterson,D;Sikela,JM
γ-氨基丁酸（GABA）受体是大脑中主要的抑制性神经递质受体，也是许多重要药理学药物（包括巴比妥类、苯二氮卓类和乙醇）的作用部位。γ 1和γ 2亚基已被证明在介导对苯二氮卓类药物的反应中是重要的，并且γ 2亚基的剪接变体γ 2L已被证明对于乙醇对受体的作用是必需的，这提高了γ 2基因可能参与人类遗传易感性以发展酒精中毒的可能性。我们已经分配的人类基因编码的γ 1和γ 2亚基的GABAA受体的染色体4和5，分别从人-仓鼠体细胞杂交DNA的人特异性产物的PCR扩增。使用染色体特异性自然缺失杂交组合的面板，我们已经进一步本地化的γ 1基因（GABRG 1）4p 14-q21.1和γ 2基因（GABRG 2）5q31.1-q33.2。这些数据表明，γ 1基因可能与先前定位的α 2和β 1基因在4号染色体上聚集在一起，γ 2基因可能接近于先前定位的α 1基因在5号染色体上。为了进一步研究后一种可能性，使用5号染色体缺失杂交体对α 1基因进行了定位，并显示其与γ 2基因在相同的区域5q31.1-q33.2内。基于PCR的筛选策略用于分离含有α 1和γ 2基因的450-脱氢酶人基因组酵母人工染色体克隆。酵母人工染色体的脉冲场凝胶限制性作图表明，这两个基因彼此在200个内切酶范围内。这里提供的数据提供了进一步的证据，证明人类基因组的非随机组织的GABAA受体基因家族的成员经常出现在小基因簇广泛分布在基因组中。
The gamma-aminobutyric acid (GABA) receptors are the major inhibitory neurotransmitter receptors in the brain and the site of action of a number of important pharmacological agents including barbiturates, benzodiazepines, and ethanol. The gamma 1 and gamma 2 subunits have been shown to be important in mediating responses to benzodiazepines, and a splicing variant of the gamma 2 subunit, gamma 2L, has been shown to be necessary for ethanol actions on the receptor, raising the possibility that the gamma 2 gene may be involved in human genetic predisposition to the development of alcoholism. We have assigned the human genes encoding the gamma 1 and gamma 2 subunits of the GABAA receptor to chromosomes 4 and 5, respectively, by PCR amplification of human-specific products from human-hamster somatic cell hybrid DNAs. Using panels of chromosome-specific natural deletion hybrids, we have further localized the gamma 1 gene (GABRG1) to 4p14-q21.1 and the gamma 2 gene (GABRG2) to 5q31.1-q33.2. These data indicate that the gamma 1 gene may be clustered together with the previously mapped alpha 2 and beta 1 genes on chromosome 4 and that the gamma 2 gene may be close to the previously localized alpha 1 gene on chromosome 5. To further examine the latter possibility the alpha 1 gene was mapped using the chromosome 5 deletion hybrids and shown to be within the same region as the gamma 2 gene, 5q31.1-q33.2. A PCR-based screening strategy was used to isolate a 450-kilobase human genomic yeast artificial chromosome clone containing both the alpha 1 and gamma 2 genes. Pulsed-field gel restriction mapping of the yeast artificial chromosome indicates that the two genes are within 200 kilobases of each other. The data presented here provide further evidence for the nonrandom organization of the human genome by demonstrating that members of the GABAA receptor gene family often occur in small gene clusters widely distributed in the genome.