Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22.
Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22.
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人类染色体 13q22 上先天性巨结肠症隐性基因的血统同一性和关联作图。
DOI：
10.1093/hmg/3.8.1217
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发表时间：
1994
影响因子：
3.5
通讯作者：
Ladda,R
中科院分区：
文献类型：
--
作者：
Puffenberger,EG;Kauffman,ER;Bolk,S;Matise,TC;Washington,SS;Angrist,M;Weissenbach,J;Garver,KL;Mascari,M;Ladda,R
先天性巨结肠是一种病因不明的先天性疾病，其特征是远端结肠缺乏肠神经节。我们已经确定了一个大的，近交，门诺家族，这表明了高发病率的先天性巨结肠症（HSCR）。对所有亲属关系的系谱分析确定了受影响后代的所有父母都有一对共同的祖先夫妇。分离分析得出男性的分离率为10.67%，女性为5.45%。我们通过对3个小的多病例家系进行基因分型，并对28个核心家系进行连锁不平衡分析，确定了家系遗传一致性的基因组区域，从而在该家系中寻找了HSCR基因的位置。基于这种新的策略，我们报告了一个新的位点HSCR染色体13q22的映射。9个微卫星标记跨越10厘米在这个地区的31个核心家庭的基因型。在标记D13S162、D13S160、D13S170和AFM240zg9处检测到与等位基因的显著非随机关联。此外，我们的研究揭示了初步证据的遗传修饰HSCR在这个家族的染色体21q22。
Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology characterized by the absence of enteric ganglia In the distal colon. We have ascertained a large, inbred, Mennonite kindred which demonstrates a high Incidence of Hirschsprung disease (HSCR). Genealogical analysis of all kinship relationships identified a single common ancestral couple for all parents of affected offspring. Segregation analysis yielded a segregation ratio of 10.67% for males and 5.45% for females. We searched for locations of the gene(s) responsible for HSCR in this pedigree by genotyplng three small multlcase families and locating genomlc regions demonstrating identity-by-descent followed by linkage disequilibrium analysis of 28 additional nuclear families. Based on this novel strategy, we report the mapping of a new locus for HSCR to chromosome 13q22. Nine microsatelllte markers spanning 10 cM in this region were genotyped on thirty-one nuclear families. Significant nonrandom association was detected with alleles at markers D13S162, D13S160, D13S170, and AFM240zg9. In addition, our studies reveal preliminary evidence for a genetic modifier of HSCR in this kindred on chromosome 21q22.