MOLECULAR GENETIC STUDIES OF CONGENITAL CATARACTS

先天性白内障的分子遗传学研究

• 批准号: 2668405
• 负责人: MICHAEL LITT
• 金额: $ 17.99万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2668405
• 关键词: autosomal dominant trait; blood chemistry; cataract; chromosome aberrations; clinical research; congenital eye disorder; crystallins; family genetics; gene expression; gene mutation; genetic markers; human genetic material tag; human subject; linkage mapping; nucleic acid sequence

We propose to map and to identify genes which cause autosomal dominant congenital cataracts (ADCC). We have mapped one such gene in an ADCC family (ADCC-1) to a region of human chromosome 22 which contains three beta-crystallin genes. Since beta-crystallins are major components of the lens, the genes which encode them are likely candidate genes for ADCC. By sequencing the coding regions and exon- intron junctions of the chromosome 22 beta-crystallin genes in ADCC-1 patients and controls, we will search for a mutation associated with the disease in this family. We have identified five additional families with ADCC. We propose to conduct linkage studies on these families to map the genes responsible for ADCC in each family. Candidate genes localized within the flanking markers identified by linkage studies will be scanned for mutations. Congenital cataracts, present at birth but not always immediately noticeable, are one of the most common major abnormalities of the eye and a frequent cause of blindness in infants. At least a third of all cases of congenital cataracts are familial and the majority of these are inherited in an autosomal dominant mode. The research proposed in this application may elucidate the mechanisms responsible for the development of congenital cataracts and hence may contribute towards more effective treatments.

我们建议映射并确定引起常染色体显性效果的基因 先天性白内障（ADCC）。 我们在ADCC中绘制了一个这样的基因 家族（ADCC-1）到22的人类染色体区域 三个β-晶状体基因。 由于β-晶状体是主要的 镜头的成分，编码它们的基因可能是 ADCC的候选基因。 通过测序编码区域和外显子 ADCC-1中22染色体β-晶状体基因的内含子连接 患者和对照组，我们将寻找与 这个家庭的疾病。 我们已经确定了另外五个与ADCC的家庭。 我们建议 对这些家族进行连锁研究以绘制负责的基因 对于每个家庭的ADCC。 候选基因本地化 通过连锁研究确定的侧翼标记将被扫描 突变。 先天性白内障，出生时，但并非总是立即 显着，是眼睛最常见的主要异常之一 和婴儿经常引起失明的原因。 至少三分之一 先天性白内障病例是家族性的，其中大多数是 以常染色体显性模式继承。 研究提出了 在此应用中，可以阐明负责 先天性白内障的发展，因此可能有助于 更有效的治疗方法。