Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22.

Journal Article (Journal Article)

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 genotyping three small multicase families and locating genomic 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 microsatellite 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.

Full Text

Duke Authors

Cited Authors

  • Puffenberger, EG; Kauffman, ER; Bolk, S; Matise, TC; Washington, SS; Angrist, M; Weissenbach, J; Garver, KL; Mascari, M; Ladda, R

Published Date

  • August 1994

Published In

Volume / Issue

  • 3 / 8

Start / End Page

  • 1217 - 1225

PubMed ID

  • 7987295

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/3.8.1217


  • eng