McGuire R E, Jordan S A, Braden V V, Bouffard G G, Humphries P, Green E D, Daiger S P
Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston 77030, USA.
Genome Res. 1996 Apr;6(4):255-66. doi: 10.1101/gr.6.4.255.
Retinitis pigmentosa is a genetically heterogeneous disease that has autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) has thus far been associated with eight distinct loci, including the rhodopsin and peripherin/RDS genes as well as unidentified genes on chromosomes 7p, 7q, 8q, 17p, 17q, and 19q. The RP10 locus for adRP on chromosome 7q was first mapped in a Spanish family; later, an unrelated American family was identified that also showed linkage to 7q. By combining the linkage results from both families, we are able to assign the disease gene to a 5-cM interval on 7q. Based on extensive physical mapping of this region, the genetic interval is now fully contained within a approximately 5-Mb segment on a well-defined YAC contig. These studies significantly reduce the size of the RP10 critical region, exclude a number of possible candidate genes, and provide the necessary cloned DNA for the positional cloning of the RP10 gene.
视网膜色素变性是一种具有遗传异质性的疾病,有常染色体显性、常染色体隐性和X连锁等形式。常染色体显性视网膜色素变性(adRP)迄今已与8个不同的基因座相关联,包括视紫红质和外周蛋白/RDS基因,以及位于7号染色体短臂、7号染色体长臂、8号染色体长臂、17号染色体短臂、17号染色体长臂和19号染色体长臂上的未明确基因。位于7号染色体长臂上的adRP的RP10基因座最初是在一个西班牙家族中定位的;后来,发现了一个不相关的美国家族,该家族也显示与7号染色体长臂连锁。通过合并两个家族的连锁结果,我们能够将致病基因定位到7号染色体长臂上一个5厘摩的区间内。基于对该区域的广泛物理图谱分析,该遗传区间现已完全包含在一个定义明确的酵母人工染色体重叠群上大约5兆碱基的片段内。这些研究显著缩小了RP10关键区域的范围,排除了一些可能的候选基因,并为RP10基因的定位克隆提供了必要的克隆DNA。