TY - JOUR
T1 - Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22
AU - G.puffenberger, Erik
AU - R.kauffman, Erick
AU - Bolk, Stacey
AU - C.matise, Tara
AU - S.washington, Sarah
AU - Angrist, Misha
AU - Weissenbach, Jean
AU - L.garver, Kenneth
AU - Mascari, Maria
AU - Ladda, Roger
AU - A.siaugenhaupt, Susan
AU - Chakravarti, Aravinda
N1 - Funding Information:
Our thanks are due to numerous individuals who aided in this research: all the Hirschsprung families and friends in the Mennonite community; Amos B.Hoover for historical and genealogical assistance; Rachel Newswanger and David J.Rempd Smucker for genealogical research; Bill and Kitty Puffenberger for meals and accommodations; and Chris Farrell and Andrew Kompanek for expert computer assistance. This work was supported in part by grants from die National Institutes of Health (HD-28088) and the Pittsburgh Genetics Institute.
PY - 1994/8
Y1 - 1994/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028069130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028069130&partnerID=8YFLogxK
U2 - 10.1093/hmg/3.8.1217
DO - 10.1093/hmg/3.8.1217
M3 - Article
C2 - 7987295
AN - SCOPUS:0028069130
SN - 0964-6906
VL - 3
SP - 1217
EP - 1225
JO - Human molecular genetics
JF - Human molecular genetics
IS - 8
ER -