title: Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis.
abstract: The identification of genetic loci involved in most forms of congenital heart disease has been hampered by the complex inheritance patterns of these disorders. Atrioventricular canal defects (AVCDs) are most commonly associated with Down syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been attributed to multifactorial inheritance. However, the occurrence of a few kindreds with multiple affected individuals has suggested that a major genetic locus can account for the disorder in some families. We have used a combination of DNA pooling and shared segment analysis to perform a high density screen of the entire autosomal human genome in an extended kindred. In so doing, we have identified a genetic locus on chromosome 1 shared by all affected individuals. Our data demonstrate the existence of a congenital heart defect susceptibility gene, inherited as an autosomal dominant with incomplete penetrance, involved in AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds in combination with high density genomic screens to identify loci involved in complex disorders such as congenital heart defects.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: M E
authors.initials: ME
authors.lastname: Pierpont
authors.forename: D
authors.initials: D
authors.lastname: Nishimura
authors.forename: J S
authors.initials: JS
authors.lastname: Beck
authors.forename: T L
authors.initials: TL
authors.lastname: Burns
authors.forename: M A
authors.initials: MA
authors.lastname: Berg
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: S R
authors.initials: SR
authors.lastname: Patil
authors.forename: R M
authors.initials: RM
authors.lastname: Lauer
mesh_terms: D002874:Chromosome Mapping; D004247:DNA; D004694:Endocardial Cushion Defects / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D004247:DNA