Genomic mapping and evolution of human GABAA receptor subunit gene clusters
Genomic mapping and evolution of human GABAA receptor subunit gene clusters
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DOI：
10.1007/s003359901101
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发表时间：
1999-08-01
期刊：
影响因子：
2.5
通讯作者：
Johnson, KJ
中科院分区：
文献类型：
--
作者：
Bailey, MES;Matthews, DA;Johnson, KJ
GABAA(-氨基丁酸A型)受体是一种异寡聚体、氯离子选择性离子通道复合体，在脊椎动物脑内抑制性神经传递中发挥重要作用。到目前为止，分子克隆研究揭示了该受体的6、3、3、1、1和1亚单位在哺乳动物中的存在(见Darlison和Albrecht 1995；Davies等人)。1997年；Hedblom和Kirkness 1997)，每个基因都由一个单独的基因编码。此外，还有证据表明存在其他哺乳动物的GABAA受体亚单位样基因(例如，见Levin等人。1996年)。这个基因家族的成员被认为是由一个共同的祖先通过复杂的基因复制过程而产生的，最终导致在四条不同的人类染色体上存在平行基因簇。本文报道了4号和5号染色体上GABAA受体亚单位基因的连锁和辐射杂交作图研究结果，包括针对2(GABRA2)、4(GABRA4)和2(GABRG2)亚单位基因的多态标记的特征，这是以前没有描述过的。我们还将编码最近鉴定的亚基(GABRP)的基因定位到Chr 5q上的一个区域，该区域位于Chr 5q33上的簇的远端，并与之分离。结合我们在Chr4基因簇中的基因序列数据，结合以前报道的Chr15和XChr基因簇中GABAA受体亚单位基因的数据，我们推断这四个已知簇中存在着古老的基因序列保守，并推测chrs4和5上的簇具有共同的祖先。
GABAA (-aminobutyric acid type A) receptors, which are heterooligomeric, chloride-selective ion-channel complexes, play a major role in inhibitory neurotransmission in the vertebrate brain. To date, molecular cloning studies have revealed the existence, in mammals, of 6, 3, 3, 1, 1 and 1 subunit of this receptor (see Darlison and Albrecht 1995; Davies et al. 1997; Hedblom and Kirkness 1997), each of which is encoded by a separate gene. In addition, evidence exists for the presence of other mammalian GABAA receptor subunit-like genes (see, for example, Levin et al. 1996). The members of this gene family are thought to have arisen from a common ancestor by a complex process of gene duplication, which has culminated in the existence of paralogous gene clusters on four different human chromosomes. We report here the results of linkage and radiation hybrid mapping studies of theGABAA receptor subunit genes on Chromosomes (Chrs) 4 and 5, including the characterization, not previously described, of polymorphic markers specific for the 2 (GABRA2), 4 (GABRA4), and 2 (GABRG2) subunit genes. We have also mapped the gene encoding the recently identified subunit (GABRP) to a region on Chr 5q that is distal to, and separate from, the cluster located in Chr 5q33. Taking our data on gene order in the cluster on Chr 4 together with the previously reported data on GABAA receptor subunit genes in the clusters on Chr 15 and the X Chr, we deduce that there has been conservation of ancient gene order within the four known clusters and suggest that the clusters on Chrs 4 and 5 shared a common ancestor.