Canine tricuspid valve malformation, a model of human Ebstein anomaly, maps to dog chromosome 9. J Med Genet 2003 May;40(5):320-4
Date
05/15/2003Pubmed ID
12746392Pubmed Central ID
PMC1735483DOI
10.1136/jmg.40.5.320Scopus ID
2-s2.0-0037900906 (requires institutional sign-in at Scopus site) 72 CitationsAbstract
BACKGROUND: Ebstein anomaly of the tricuspid valve is a congenital cardiac malformation characterised by downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Canine tricuspid valve malformation (CTVM) is morphologically similar to Ebstein anomaly; familial occurrence of CTVM has been described. Several observations suggest a genetic cause but most cases appear to be sporadic.
METHODS: Three purebred Labrador Retriever kindreds enriched for CTVM underwent clinical examination and echocardiography. DNA was extracted from whole blood. Genotyping was carried out using polymorphic repeat markers with an average spacing of 15 cM and polymorphic information content of 0.74.
RESULTS: Pedigree analysis identified CTVM segregating as an autosomal dominant trait with reduced penetrance. Genome wide linkage analysis in one kindred identified a CTVM susceptibility locus on dog chromosome 9 (CFA9) with a maximum multipoint lod score of 3.33. The two additional kindreds showed a conserved disease haplotype.
CONCLUSIONS: This study identifies a CTVM susceptibility locus on CFA9 and a founder effect in apparently unrelated Labrador Retriever kindreds. These results provide the basis for a positional candidate cloning effort to identify the CTVM disease gene. Identification of the CTVM gene will permit mutation screening of patients with Ebstein anomaly, which should provide additional insights into the genetic programmes of valve development.
Author List
Andelfinger G, Wright KN, Lee HS, Siemens LM, Benson DWMESH terms used to index this publication - Major topics in bold
AnimalsChromosome Mapping
Chromosomes, Mammalian
Disease Models, Animal
Dogs
Ebstein Anomaly
Female
Founder Effect
Genes, Dominant
Genetic Predisposition to Disease
Haplotypes
Humans
Lod Score
Male
Pedigree
Penetrance
Tricuspid Valve
Ultrasonography