The study of morphology in the PWD represents one of the most interesting stories from the canine genetics community to date. PWD of today are descended from a small number of dogs primarily from two kennels [54,55]. Six ancestors account for about 80% of the current gene pool of 10,000 dogs, and the breed is characterized, in part, by extensive consanguinity, with a range of 0–0.6 [56].
Through a program termed the Georgie Project (http://www.georgieproject.com), investigators at the University of Utah, Gordon Lark, Kevin Chase, and collaborators, have collected extensive phenotypic data (five sets of X rays on over 500) and genotypic data (DNA samples of over 900) on registered PWDs. Ninety-one metrics describing aspects of canine morphology have been extracted from the X rays, and DNA samples have been genotyped with nearly 500 microsatellite markers that span the genome at about 5centimorgan density.
In 2002, a subset of the data was subjected to principal component analysis, which classifies variation of correlated traits into independent linear combinations. Principal component 4, for instance, demonstrates how skull and limb lengths are inversely correlated with the strength of the limb and axial skeletons. Bulldogs have proportionately shorter, wider bones designed to accommodate large body mass, while the greyhound's long, thin limbs are adapted for speed (see Figure 1). Analysis of these data has highlighted 44 putative QTLs on 22 chromosomes that are important for heritable skeletal phenotypes in the PWD [57]. Ongoing collaborations between our own laboratory and Gordon Lark, Kevin Chase, and collaborators are aimed at finding the specific variants responsible for each principal component.
Among the most satisfying aspects of this work has been the ability to demonstrate how canine genetics allows us to unravel complex, but nonadditive, interactions between genetic loci, a problem which has proven difficult to approach using classical genetic methods. For example, 21% of the observed variation in skeletal size among PWDs results from differences between females and males. Analysis of the above dataset suggests that more than half of this sexual dimorphism results from an interaction between a QTL linked to canine Chromosome 15 and a locus adjacent to the CHM gene on the X chromosome [58]. In females, the haplotype associated with small size on canine Chromosome 15 is dominant, while in males it is the reverse—the haplotype associated with larger size is dominant. The introduction of the X chromosome locus complicates the story, but explains some curious observations as well. For instance, in any population of PWDs, there are always a small number of females who are as large as the largest males. Analysis of the X chromosome locus shows that females who are homozygous for both the CHM linked marker as well as the haplotype associated with large size on canine Chromosome 15 will be, on average, as large as the largest males [58]. Modifier genes such as the one on the X chromosome, which by themselves do not have a detectable effect, would not be identified using traditional QTL methods, highlighting again the value of this approach.
Answers to all your Biology Questions
