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Principal Investigator: Dr. Rory Todhunter
Contact Information: E-mail: rjt2@cornell.edu - Phone: 3-3249
Sponsor: Morris Animal Foundation
Grant Number: D04CA-135
Title: Mapping Refinement of Quantitative Trait Loci for Canine
Hip Dysplasia
Annual Direct Cost: $131,758
Project Period: 9/1/04-8/31/06
To discover the mutations underlying canine hip dysplasia (CHD), we bred dysplastic Labrador Retrievers with trait-free Greyhounds. To find the genes that contribute to CHD that are localized in chromosomal regions called quantitative trait loci (QTL), a 240-marker, genome-wide scan was undertaken on 147 dogs of this 4-generation pedigree. Statistical analysis revealed significant QTL on 16 autosomes and the X chromosome that putatively contribute to expression of CHD. Validating these mapping results by genotyping more individuals with a dense microsatellite set and undertaking additional statistical analysis is imperative to precise localization and ranking of the contributing QTL.
Our long-term hypothesis is that precise localization of quantitative trait loci for canine hip dysplasia will lead to discovery of the contributing genes and their mutations. The objectives of this proposal are:
A. To define their location and to rank the putative QTL contributing to the hip traits of 160 Greyhound/Labrador Retrievers and 160 Labrador Retrievers genotyped at 500 microsatellite loci.
B. To fine map QTL at 1-2 cM intervals on canine chromosomes 29 and 33 and additional QTL based on results of Specific Aim 1.
C. To breed informative backcross individuals (F1 X Labrador Retriever) and to accumulate hip trait measures and DNA on 1000 dogs unrelated to the Cornell pedigrees and develop single nucleotide polymorphism haplotypes associated with CHD.
The hip traits and DNA on these 1000 dogs will be used for linkage disequilibrium mapping with single nucleotide polymorphisms (SNPs). Conservation of the same susceptibility regions across dogs within breeds and across breeds will validate their contribution to CHD expression. Linkage disequilibrium mapping will narrow the contributing QTL intervals for subsequent candidate gene selection and mutation screening.
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