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Mapping of a Hirschsprung's disease locus in 3p21
- Source :
- European journal of human genetics : EJHG. 16(7)
- Publication Year :
- 2008
-
Abstract
- Hirschsprung's disease (HSCR) is a congenital disorder in which ganglion cells are absent in variable portions of the lower digestive tract according to which patients are classified. The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required. An unidentified RET-dependent modifier on 3p21 appears to be necessary for transmission of the short HSCR (S-HSCR) phenotype. We investigated 6 Mb of the 3p21 region on a quest for the HSCR-susceptibility locus. Fifty-eight S-HSCR case-parent trios were genotyped using Sequenom technology for 214 tag single nucleotide polymorphisms (SNPs) distributed along 6 Mb of the 3p21 region. A five-marker haplotype, spanning a 118 kb gene-rich region, was found to be overtransmitted to affected offspring. The associated haplotype encompasses three genes involved in neurological phenotypes. Importantly, this association was replicated in an independent sample of 172 S-HSCR cases and 153 unrelated controls. Ranking markers by proximity to candidate genes or by expected functional consequences could be used in follow-up studies to finally pinpoint this HSCR locus.
- Subjects :
- Genetic Markers
Male
Quality Control
Candidate gene
Single-nucleotide polymorphism
Locus (genetics)
Biology
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Gene mapping
Asian People
Genetics
medicine
Humans
Family
Genetic Predisposition to Disease
Hirschsprung Disease
Hirschsprung's disease
Gene
Genetics (clinical)
Haplotype
Chromosome Mapping
medicine.disease
Penetrance
Haplotypes
Case-Control Studies
Female
Chromosomes, Human, Pair 3
Subjects
Details
- ISSN :
- 10184813
- Volume :
- 16
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- European journal of human genetics : EJHG
- Accession number :
- edsair.doi.dedup.....3738c8943fe9904322ec673a9fe6ded6