title: Construction of a high-resolution physical map of the chromosome 10q22-q23 dilated cardiomyopathy locus and analysis of candidate genes.
abstract: Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality and a leading cause of cardiac transplantation worldwide. Multiple loci and three genes encoding cardiac actin, desmin, and lamin A/C have been described for autosomal dominant DCM. Using recombination analysis, we have narrowed the 10q21-q23 locus to a region of approximately 4.1 cM. In addition, we have constructed a BAC contig, composed of 199 clones, which was used to develop a high-resolution physical map that contains the DCM critical region (approximately 3.9 Mb long). Seven genes, including ANX11, PPIF, DLG5, RPC155, RPS24, SFTPA1, and KCNMA1, have been mapped to the region of interest. RPC155, RPS24, SFTPA1, and KCNMA1 were excluded from further analysis based on their known functions and tissue-specific expression patterns. Mutational analysis of ANX11, DLG5, and PPIF revealed no disease-associated mutations. Multiple ESTs have also been mapped to the critical region.
authors.affiliation: Department of Molecular and Human Genetics, Department of Pediatrics (Cardiology), Department of Medicine, Department of Cardiovascular Sciences, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Bowles
authors.forename: S E
authors.initials: SE
authors.lastname: Abraham
authors.forename: R
authors.initials: R
authors.lastname: Brugada
authors.forename: C
authors.initials: C
authors.lastname: Zintz
authors.forename: J
authors.initials: J
authors.lastname: Comeaux
authors.forename: D
authors.initials: D
authors.lastname: Sorajja
authors.forename: S
authors.initials: S
authors.lastname: Tsubata
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Brandon
authors.forename: R A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: S E
authors.initials: SE
authors.lastname: Scherer
authors.forename: N E
authors.initials: NE
authors.lastname: Bowles
authors.forename: J A
authors.initials: JA
authors.lastname: Towbin
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002876:Chromosomes, Bacterial; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004252:DNA Mutational Analysis; D020224:Expressed Sequence Tags; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015698:Genomic Library; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA