通过7q31染色体区域的高分辨率物理图谱鉴定出的先天性氯化物腹泻的定位候选基因。

Positional candidate genes for congenital chloride diarrhea suggested by high-resolution physical mapping in chromosome region 7q31.

作者信息

Höglund P, Haila S, Scherer S W, Tsui L C, Green E D, Weissenbach J, Holmberg C, de la Chapelle A, Kere J

机构信息

Department of Medical Genetics, University of Helsinki, Finland.

出版信息

Genome Res. 1996 Mar;6(3):202-10. doi: 10.1101/gr.6.3.202.

DOI:10.1101/gr.6.3.202

PMID:8963897

Abstract

Congenital chloride diarrhea affects intestinal transportation of electrolytes, resulting in potentially fatal diarrhea. Linkage disequilibrium analyses have suggested the congenital chloride diarrhea gene (CLD) to lie within 0.37 cM from D7S496 in human chromosome 7q31. To clone the CLD gene, we have constructed and refined a physical map based on a 2.7-Mb YAC contig around D7S496 and identified two candidate genes. The physical positions of 4 known genes (DRA, PRKAR2B, LAMB1, DLD), 7 polymorphic repeat markers, and 13 CpG islands were established. DRA (down-regulated in adenoma) is expressed in the gut and encodes a protein with sequence homology to anion transporters, whereas PRKAR2B encodes a regulatory subunit for protein kinase A. Both genes map within 450 kb from D7S496, making them functionally and positionally relevant candidates for CLD.

摘要

先天性氯腹泻影响肠道电解质转运，导致可能致命的腹泻。连锁不平衡分析表明，先天性氯腹泻基因（CLD）位于人类染色体7q31上距D7S496 0.37 cM范围内。为了克隆CLD基因，我们基于围绕D7S496的2.7 Mb酵母人工染色体（YAC）重叠群构建并完善了一个物理图谱，并鉴定了两个候选基因。确定了4个已知基因（DRA、PRKAR2B、LAMB1、DLD）、7个多态性重复标记和13个CpG岛的物理位置。DRA（腺瘤中下调）在肠道中表达，编码一种与阴离子转运体具有序列同源性的蛋白质，而PRKAR2B编码蛋白激酶A的调节亚基。这两个基因均位于距D7S496 450 kb范围内，使其成为CLD在功能和位置上的相关候选基因。