title: Genetic structure of susceptibility traits for hip dysplasia and microsatellite informativeness of an outcrossed canine pedigree.
abstract: An outcrossed canine pedigree was developed for quantitative trait locus (QTL) mapping of hip dysplasia by breeding dysplastic Labrador retrievers to trait-free greyhounds. Measured susceptibility traits included age at onset of femoral capital chondroepiphyseal ossification (OSS), maximum hip distraction (laxity) index (DI), and the dorsolateral subluxation (DLS) score. The pedigrees consisted of 147 dogs representing four generations. For 59 dogs genotyped with 65 microsatellites, the median heterozygosity and polymorphic information content (PIC) values of the F(1) generation were 0.82 and 0.68, respectively. Seventy-seven percent of microsatellites had a PIC greater than 0.59 in the F(1)s. Ninety-six percent of alleles showed Mendelian inheritance. Based on marker informativeness, approximately 350 randomly selected markers would be required for genome-wide screening to obtain an average interval between informative markers of 10 cM. Heritability was estimated as 0.43, 0.5, and 0.61 for OSS, DI, and the DLS score, respectively. Biometric estimates of the mean (+/- variance) effective number of segregating QTLs was 1.2 (+/- 0.05), 0.8 (+/- 0.02), and 1.0 (+/- 0.03) for OSS, DI, and the DLS score, respectively. The distributions of simulated backcross trait data suggested that the loci controlling these traits acted additively and that the DI may be controlled by a major locus. When combined with previous power and quantitative genetic analyses, these estimates indicate that this pedigree is informative for QTL mapping of hip dysplasia traits.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA. rjt2@cornell.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Todhunter
authors.forename: S P
authors.initials: SP
authors.lastname: Bliss
authors.forename: G
authors.initials: G
authors.lastname: Casella
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Lust
authors.forename: N I
authors.initials: NI
authors.lastname: Burton-Wurster
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
authors.forename: R O
authors.initials: RO
authors.lastname: Gilbert
authors.forename: G M
authors.initials: GM
authors.lastname: Acland
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004285:Dogs / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006619:Hip Dysplasia, Canine / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D040641:Quantitative Trait Loci