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

Hum Mol Genet. 1994 Aug;3(8):1217-25. doi: 10.1093/hmg/3.8.1217.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping*
  • Chromosomes, Human, Pair 13*
  • Female
  • Genes, Recessive / genetics*
  • Haplotypes
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Pedigree