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

Erik G.puffenberger, Erick R.kauffman, Stacey Bolk, Tara C.matise, Sarah S.washington, Misha Angrist, Jean Weissenbach, Kenneth L.garver, Maria Mascari, Roger Ladda, Susan A.siaugenhaupt, Aravinda Chakravarti

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1217-1225
Number of pages9
JournalHuman molecular genetics
Volume3
Issue number8
DOIs
StatePublished - Aug 1 1994

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Recessive Genes
Hirschsprung Disease
Human Chromosomes
Nuclear Family
Chromosomes
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Linkage Disequilibrium
Pedigree
Ganglia
Colon
Parents
Alleles
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

G.puffenberger, E., R.kauffman, E., Bolk, S., C.matise, T., S.washington, S., Angrist, M., ... Chakravarti, A. (1994). Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22. Human molecular genetics, 3(8), 1217-1225. https://doi.org/10.1093/hmg/3.8.1217
G.puffenberger, Erik ; R.kauffman, Erick ; Bolk, Stacey ; C.matise, Tara ; S.washington, Sarah ; Angrist, Misha ; Weissenbach, Jean ; L.garver, Kenneth ; Mascari, Maria ; Ladda, Roger ; A.siaugenhaupt, Susan ; Chakravarti, Aravinda. / Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22. In: Human molecular genetics. 1994 ; Vol. 3, No. 8. pp. 1217-1225.
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G.puffenberger, E, R.kauffman, E, Bolk, S, C.matise, T, S.washington, S, Angrist, M, Weissenbach, J, L.garver, K, Mascari, M, Ladda, R, A.siaugenhaupt, S & Chakravarti, A 1994, 'Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22', Human molecular genetics, vol. 3, no. 8, pp. 1217-1225. https://doi.org/10.1093/hmg/3.8.1217

Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22. / G.puffenberger, Erik; R.kauffman, Erick; Bolk, Stacey; C.matise, Tara; S.washington, Sarah; Angrist, Misha; Weissenbach, Jean; L.garver, Kenneth; Mascari, Maria; Ladda, Roger; A.siaugenhaupt, Susan; Chakravarti, Aravinda.

In: Human molecular genetics, Vol. 3, No. 8, 01.08.1994, p. 1217-1225.

Research output: Contribution to journalArticle

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

PY - 1994/8/1

Y1 - 1994/8/1

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.

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G.puffenberger E, R.kauffman E, Bolk S, C.matise T, S.washington S, Angrist M et al. Identity-by-descent and association mapping of a recessive gene for hirschsprung disease on human chromosome 13q22. Human molecular genetics. 1994 Aug 1;3(8):1217-1225. https://doi.org/10.1093/hmg/3.8.1217