Kermani S, Gregory-Evans K, Tarttelin E E, Bellingham J, Plant C, Bird A C, Fox M, Bhattacharya S S, Gregory-Evans C Y
Department of Molecular Genetics, Institute of Ophthalmology, London, UK.
Hum Genet. 1999 Jan;104(1):77-82. doi: 10.1007/s004390050913.
Doyne honeycomb retinal dystrophy (DHRD) is a late-onset autosomal dominant disorder that causes degeneration of the retina and can lead to blindness. We have previously assigned DHRD to a 5-cM region of chromosome 2p16 between marker loci D2S2739 and D2S378. Using sequence-tagged sites (STSs), expressed sequence tags (ESTs) and polymorphic markers within the DHRD region, we have identified 18 yeast artificial chromosomes (YACs) encompassing the DHRD locus, spanning approximately 3 Mb. The YAC contig was constructed by STS content mapping of these YACs and incorporates 13 STSs, including four genes and six polymorphic marker loci. We also report the genetic mapping of two families with a dominant drusen phenotype to the DHRD locus, and genetic refinement of the disease locus to a critical interval flanked by microsatellite marker loci D2S2352 and D2S2251, a distance of approximately 700 kb. These studies exclude a number of candidate genes and provide a resource for construction of a transcriptional map of the region, as a prerequisite to identification of the DHRD disease-causing gene and genes for other diseases mapping in the region, such as Malattia leventinese and Carney complex.
多伊内蜂窝状视网膜营养不良（DHRD）是一种迟发性常染色体显性疾病，可导致视网膜变性并可能导致失明。我们之前已将DHRD定位到2号染色体p16区域一个5厘摩的区间，位于标记位点D2S2739和D2S378之间。利用DHRD区域内的序列标签位点（STS）、表达序列标签（EST）和多态性标记，我们鉴定出18个包含DHRD基因座的酵母人工染色体（YAC），覆盖约3兆碱基。通过对这些YAC进行STS含量作图构建了YAC重叠群，该重叠群包含13个STS，其中包括4个基因和6个多态性标记位点。我们还报告了两个具有显性玻璃疣表型的家系与DHRD基因座的遗传定位，以及将疾病基因座精细定位到由微卫星标记位点D2S2352和D2S2251界定的关键区间，距离约为700千碱基。这些研究排除了一些候选基因，并为构建该区域的转录图谱提供了资源，这是鉴定DHRD致病基因以及该区域其他疾病相关基因（如莱文廷病和卡尼综合征）的先决条件。
