常染色体显性视网膜色素变性RP17基因座的精细定位、酵母人工染色体重叠群的构建及候选基因视网膜丝束蛋白的研究

Refinement of the RP17 locus for autosomal dominant retinitis pigmentosa, construction of a YAC contig and investigation of the candidate gene retinal fascin.

作者信息

Bardien-Kruger S, Greenberg J, Tubb B, Bryan J, Queimado L, Lovett M, Ramesar R S

机构信息

Department of Human Genetics, University of Cape Town, South Africa.

出版信息

Eur J Hum Genet. 1999 Apr;7(3):332-8. doi: 10.1038/sj.ejhg.5200302.

DOI:10.1038/sj.ejhg.5200302

PMID:10234509

Abstract

The RP17 locus for autosomal dominant retinitis pigmentosa has previously been mapped to chromosome 17q by linkage analysis. Two unrelated South African families are linked to this locus and the identification of key recombination events assigned the RP17 locus to a 10 cM interval on 17q22. The work reported here refines the mapping of the locus from a 10 cM to a 1 cM interval between the microsatellite markers D17S1604 and D17S948. A physical map of this interval was constructed using information from the Whitehead/MIT YAC contig WC 17.8. Sequence-tagged site (STS) content mapping of seven overlapping YACs from this contig was employed in order to build the map. A BAC library was screened to cover a gap in the YAC contig and two positive BACs were identified. Intragenic polymorphisms in the retinal fascin gene provided evidence for the exclusion of this candidate as the RP17 disease gene.

摘要

常染色体显性遗传性视网膜色素变性的RP17基因座先前已通过连锁分析定位到17号染色体q区。两个无亲缘关系的南非家族与该基因座连锁，通过对关键重组事件的鉴定，将RP17基因座定位到17q22上一个10厘摩的区间。本文报道的工作将该基因座的定位从10厘摩区间精细到微卫星标记D17S1604和D17S948之间的1厘摩区间。利用来自Whitehead/MIT酵母人工染色体（YAC）重叠群WC 17.8的信息构建了该区间的物理图谱。为构建图谱，对来自该重叠群的7个重叠YAC进行了序列标签位点（STS）含量作图。筛选了一个细菌人工染色体（BAC）文库以覆盖YAC重叠群中的一个缺口，并鉴定出两个阳性BAC。视网膜丝束蛋白基因中的基因内多态性为排除该候选基因作为RP17疾病基因提供了证据。