通过定位克隆分离诺里病的一个候选基因。

Isolation of a candidate gene for Norrie disease by positional cloning.

作者信息

Berger W, Meindl A, van de Pol T J, Cremers F P, Ropers H H, Döerner C, Monaco A, Bergen A A, Lebo R, Warburg M

机构信息

Department of Human Genetics, University of Nijmegen, The Netherlands.

出版信息

Nat Genet. 1992 Jun;1(3):199-203. doi: 10.1038/ng0692-199.

DOI:10.1038/ng0692-199

PMID:1303235

Abstract

The gene for Norrie disease, an X-linked disorder characterized by progressive atrophy of the eyes, mental disturbances and deafness, has been mapped to chromosome Xp11.4 close to DXS7 and the monoamine oxidase (MAO) genes. By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene. With one of these cosmids, microdeletions were detected in several patients with Norrie disease. Screening of cDNA libraries has enabled us to isolate and sequence a likely candidate gene for Norrie disease which is expressed in retina, choroid and fetal brain. No homologous sequences were found in DNA and protein databases indicating that this cDNA is part of a gene encoding a 'pioneer' protein.

摘要

诺里病是一种X连锁疾病，其特征为眼睛进行性萎缩、精神障碍和耳聋。该疾病的基因已被定位到X染色体p11.4，靠近DXS7和单胺氧化酶（MAO）基因。通过亚克隆一个带有640千碱基（kb）插入片段的酵母人工染色体（YAC），该插入片段跨越DXS7 - MAOB区间，我们构建了一个黏粒重叠群，它延伸至MAOB基因之外250 kb处。利用其中一个黏粒，在数名诺里病患者中检测到了微缺失。对cDNA文库的筛选使我们能够分离并测序一个可能的诺里病候选基因，该基因在视网膜、脉络膜和胎儿脑中表达。在DNA和蛋白质数据库中未发现同源序列，这表明该cDNA是一个编码“先驱”蛋白的基因的一部分。