Oohashi T, Ueki Y, Sugimoto M, Ninomiya Y
Department of Molecular Biology and Biochemistry, Okayama University Medical School, Japan.
J Biol Chem. 1995 Nov 10;270(45):26863-7. doi: 10.1074/jbc.270.45.26863.
The genes COL4A5 and COL4A6, coding for the basement membrane collagen chains, alpha 5(IV) and alpha 6(IV), respectively, are located head-to-head in close proximity on human chromosome Xq22, and COL4A6 is transcribed from two alternative promoters in a tissue-specific fashion (Sugimoto M., Oohashi T., and Ninomiya Y. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 11679-11683). Immunofluorescence studies using alpha chain-specific antibodies demonstrated that the two genes are expressed in a tissue-specific manner (Ninomiya, Y., Kagawa, M., Iyama, K., Naito, L., Kishiro, Y., Seyer, J. M., Sugimoto, M., Oohashi, T., and Sado, Y. (1995) J. Cell Biol. 130, 1219-1229). We report here for the first time the isolation and the structural organization of the human COL4A6 gene. The entire gene presumably exceeds 200 kilobase pairs and contains 46 exons. Exons 1' and 1 encode the two different 5'-UTRs and the two amino-terminal parts of of the signal peptide. The carboxyl part of the signal peptide and the 7 S domain are coded for by the following 6 different exons, 2-7, whereas the exons 7-42 encode the central COL 1 domain, which contains the Gly-X-Y repeats. The last three exons, 43-45, encode the carboxyl-terminal NC1 domain. Sizes of more than a half of the exons of the gene are the same as those of Col4a2 but quite different from those of COL4A5. Within the COL4A6 gene we found three CA repeat markers that can be used for allele detection. The detailed structure of the COL4A6 gene and the high heterozygosity microsatellite markers located within the gene will be useful for linkage analysis and familial diagnosis of diseases caused by mutations of this gene.
分别编码基底膜胶原链α5(IV)和α6(IV)的基因COL4A5和COL4A6，在人类X染色体Xq22上紧密相邻且头对头排列，并且COL4A6以组织特异性方式从两个可变启动子转录（杉本M.、大桥T.和二宫Y.（1994年）《美国国家科学院院刊》91，11679 - 11683）。使用α链特异性抗体的免疫荧光研究表明这两个基因以组织特异性方式表达（二宫Y.、川合M.、石山K.、内藤L.、岸郎Y.、塞耶J.M.、杉本M.、大桥T.和佐渡Y.（1995年）《细胞生物学杂志》130，1219 - 1229）。我们在此首次报告人类COL4A6基因的分离及其结构组织。整个基因可能超过200千碱基对，包含46个外显子。外显子1'和1编码两个不同的5'非翻译区以及信号肽的两个氨基末端部分。信号肽的羧基部分和7S结构域由接下来的6个不同外显子2 - 7编码，而外显子7 - 42编码包含甘氨酸 - X - 酪氨酸重复序列的中央COL 1结构域。最后三个外显子43 - 45编码羧基末端NC1结构域。该基因一半以上外显子的大小与Col4a2的相同，但与COL4A5的外显子大小有很大差异。在COL4A6基因内我们发现了三个可用于等位基因检测的CA重复标记。COL4A6基因的详细结构以及位于该基因内的高杂合性微卫星标记将有助于该基因突变所致疾病的连锁分析和家族诊断。
