Höglund P, Sistonen P, Norio R, Holmberg C, Dimberg A, Gustavson K H, de la Chapelle A, Kere J
Department of Medical Genetics, University of Helsinki, Finland.
Am J Hum Genet. 1995 Jul;57(1):95-102.
Congenital chloride diarrhea is a recessively inherited intestinal disorder affecting electrolyte transportation. The clinical presentation is a life-threatening watery diarrhea with a high chloride content. Recently, the congenital chloride diarrhea gene (CLD) was assigned to chromosome 7 by linkage in eight Finnish families. In the present study, refined mapping of CLD was performed by studying linkage and linkage disequilibrium in 24 Finnish and 4 Swedish families. Recombination mapping assigned CLD to an approximately 10-cM region flanked by D7S515 and D7S799. Linkage disequilibrium was detected over this large genetic region, with the strongest allelic association at D7S496. Application of the Luria and Delbrück-derived analysis allowed for a further narrowing of the CLD region to approximately 0.37 cM from the marker D7S496. Haplotype analysis placed CLD unequivocally between D7S501 and D7S692, very close to D7S496 and most likely on the distal side of D7S496. This combined analytical approach allowed highly accurate mapping of CLD, each component adding complementary and consistent mapping information.
先天性氯化物腹泻是一种隐性遗传的肠道疾病，影响电解质转运。临床表现为危及生命的高氯性水样腹泻。最近，通过对八个芬兰家族的连锁分析，先天性氯化物腹泻基因（CLD）被定位到7号染色体上。在本研究中，通过对24个芬兰家族和4个瑞典家族进行连锁分析和连锁不平衡研究，对CLD进行了精细定位。重组定位将CLD定位于由D7S515和D7S799侧翼的大约10厘摩区域。在这个大的遗传区域检测到连锁不平衡，在D7S496处等位基因关联最强。应用卢里亚和德尔布吕克衍生的分析方法，可将CLD区域从标记D7S496进一步缩小到约0.37厘摩。单倍型分析明确将CLD定位在D7S501和D7S692之间，非常靠近D7S496，最有可能在D7S496的远端。这种综合分析方法实现了CLD的高精度定位，每个组成部分都提供了互补且一致的定位信息。
