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The keeshond defect in cardiac conotruncal development is oligogenic
Petra Werner1, Michael G Raducha, Ulana Prociuk
1Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancy Street, Philadelphia, PA 19104-6010, USA. pwerner@vet.upenn.edu
Human Genetics
|February 16, 2005
Summary
Genetic studies in keeshond dogs reveal that conotruncal defects (CTDs) involve multiple genetic loci on chromosomes 2, 9, and 15. These findings suggest complex inheritance patterns for this cardiac malformation.
Area of Science:
- Veterinary Genetics
- Cardiovascular Research
- Canine Health
Background:
- Conotruncal defects (CTDs) are a spectrum of related cardiac malformations affecting dogs and humans.
- Previous research suggested a single autosomal recessive trait for CTD susceptibility in keeshonds.
- Complex, multifactorial inheritance is often assumed for non-syndromic CTDs.
Purpose of the Study:
- To identify genetic loci associated with CTDs in a keeshond x beagle backcross pedigree.
- To investigate the inheritance pattern of CTDs beyond a single susceptibility locus.
Main Methods:
- Genome-wide scan utilizing a keeshond x beagle F1 backcross pedigree.
- Two-point and multipoint linkage analysis using Genehunter software.
- Comparative mapping of canine linked regions to human chromosomal locations.
Main Results:
- Two-point linkage analysis identified suggestive linkage regions on canine chromosomes (CFA) 2, 9, and 15.
- Multipoint analysis yielded a corrected LOD score of 3.7 for a locus on CFA9, with support for CFA2 and CFA15.
- No single locus explained CTD segregation, indicating involvement of multiple loci.
Conclusions:
- CTD development in this canine model likely requires alleles from at least two of the identified loci on CFA2, CFA9, and CFA15.
- Canine CTD-linked regions are orthologous to human chromosomal regions implicated in cardiac development.
- Further research is expected to identify novel genes contributing to CTD etiology.