title: Genome-wide high-density SNP-based linkage analysis of infantile hypertrophic pyloric stenosis identifies loci on chromosomes 11q14-q22 and Xq23.
abstract: Infantile hypertrophic pyloric stenosis (IHPS) has an incidence of 1-8 per 1000 live births and is inherited as a complex sex-modified multifactorial trait with a striking male preponderance. Syndromic and monogenic forms exist, and two loci have been identified. Infants present with vomiting due to gastric-outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. A genome-wide SNP-based high-density linkage scan was carried out on 81 IHPS pedigrees. Nonparametric and parametric linkage analysis identified loci on chromosomes 11q14-q22 (Z(max) = 3.9, p < 0.0001; HLOD(max) = 3.4, alpha = 0.34) and Xq23 (Z(max) = 4.3, p < 0.00001; HLOD(max) = 4.8, alpha = 0.56). The two linked chromosomal regions each harbor functional candidate genes that are members of the canonical transient receptor potential (TRPC) family of ion channels and have a potential role in smooth-muscle control and hypertrophy.
authors.affiliation: University College London Institute of Child Health, London WC1N 1EH, UK. kate.everett@ucl.ac.uk
authors.forename: Kate V
authors.initials: KV
authors.lastname: Everett
authors.forename: Barry A
authors.initials: BA
authors.lastname: Chioza
authors.forename: Christina
authors.initials: C
authors.lastname: Georgoula
authors.forename: Ashley
authors.initials: A
authors.lastname: Reece
authors.forename: Francesca
authors.initials: F
authors.lastname: Capon
authors.forename: Keith A
authors.initials: KA
authors.lastname: Parker
authors.forename: Cathy
authors.initials: C
authors.lastname: Cord-Udy
authors.forename: Paul
authors.initials: P
authors.lastname: McKeigue
authors.forename: Sally
authors.initials: S
authors.lastname: Mitton
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Mitchison
authors.forename: Eddie M K
authors.initials: EM
authors.lastname: Chung
authors.forename: R Mark
authors.initials: RM
authors.lastname: Gardiner
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D046248:Pyloric Stenosis, Hypertrophic / Q000235:genetics*; D012744:Sex Ratio