Genetic mapping of principal components of canine pelvic morphology

Canine Genet Epidemiol. 2017 Mar 24:4:4. doi: 10.1186/s40575-017-0043-7. eCollection 2017.

Abstract

Background: Concentrated breeding effort to produce various body structures and behaviors of dogs to suit human demand has inadvertently produced unwanted traits and diseases that accompany the morphological and behavioral phenotypes. We explored the relationship between pelvic conformation and canine hip dysplasia (HD) because purebred dogs which are predisposed, or not, to HD share common morphologic features, respectively. Thirteen unique bilateral anatomical features of the pelvis were measured on 392 dogs of 51 breeds and 95 mixed breed dogs. Principal components (PCs) were derived to describe pelvic morphology. Dogs were genotyped at ~183,000 single nucleotide polymorphisms and their hip conformation was measured by the Norberg angle and angle of inclination between the femoral neck and diaphysis.

Results: No associations reached genome wide significance for the Norberg angle when averaged over both hips. PC1 was negatively correlated with the Norberg angle (r = -0.31; P < 0.05) but not the angle of inclination (r = -0.08; P > 0.05). PC1, 2, 4, and 5 differed significantly between male and female dogs confirming pelvic sexual dimorphism. With sex as a covariate, the eigenvector contribution to PC1 reflected the overall size of the pelvis and was significantly associated with the IGF-1 locus, a known contributor to canine body size. PC3, which represented a tradeoff between ilial length and ischial length in which a longer ischium is associated with a shorter ilium, was significantly associated with a marker on canine chromosome 16:5181388 bp. The closest candidate gene is TPK1, a thiamine-dependent enzyme and part of the PKA complex. Associations with the remaining PCs did not reach genome wide significance.

Conclusion: IGF-1 was associated with the overall size of the pelvis and sex is related to pelvic size. Ilial/ischial proportion is genetically controlled and the closest candidate gene is thiamine-dependent and affects birth weight and development of the nervous system. Dogs with larger pelves tend to have smaller NAs consistent with increased tendency toward HD in large breed dogs. Based on the current study, pelvic shape alone was not strongly associated with canine hip dysplasia.

Keywords: Dog; GWAS; Hip dysplasia; IGF-1; Norberg angle; Pelvic sexual dimorphism; Principal component analysis.