Genetic analysis of canine hip dysplasia

摘要

The morphologic variability seen in the domestic dog, Canis lupus familiaris, isunique among mammals. Selective pressures imposed by humans have divided dogs intoalmost 400 separate breeds. Selection has also led to the development of approximately450 hereditary diseases, many of which are limited to specific breeds. Over half of thesediseases present with similar clinical characteristics to those of many human hereditarydiseases, making the dog an ideal model for study of the genetic bases of such diseases.Many diseases do not have candidate genes or have too many candidates to characterize.This is exacerbated in complex diseases that are caused by several genes. Whole-genomescans can provide insight into diseases by identifying marker(s) that co-segregate with adisease phenotype. The Minimal Screening Set - 2 (MSS-2) is the most recent set ofmicrosatellites suitable for whole-genome screens. The first objective of this work wasto streamline genomic screens in order to efficiently analyze large numbers of animals.To this end, chromosome-specific microsatellite panels were developed for the MSS-2.Canine hip dysplasia (CHD) is the most common orthopedic disease of the dog.CHD primarily affects medium and large breed dogs, but is found in almost every breed.The major objective of this work was to use linkage analysis to identify chromosomalregions that contain genes that are involved in CHD. Two populations were screenedusing the MSS-2. The first was a small family of Boykin Spaniels, though no markers were statistically significant in a whole-genome screen. An outcrossed pedigree ofGreyhound/Labrador Retrievers was created for quantitative trait loci (QTL) mapping ofCHD. The informativeness of markers in the F2 and backcrossed generations werecalculated to show the utility of using such a population. Other factors that affect thepower of this pedigree to identify QTL were also highlighted. Chromosomes that wereidentified in a previous screen as harboring putative QTLs were examined using thechromosome-specific panels to further define and confirm the regions of interest.Although no markers reached statistical significance, several areas of interest wereidentified.