Deletions in the COL10A1 gene are not associated with skeletal changes in dogs.

Type 10 collagen alpha 1 (COL10A1) is a short-chain collagen of cartilage synthesized by chondrocytes during the growth of long bones. COL10A1 mutations, which frequently result in COL10A1 haploinsufficiency, have been identified in patients with Schmid metaphyseal chondrodysplasia (SMCD), a cartilage disorder characterized by short-limbed short stature and bowed legs. Similarities between SMCD and short stature in various dog breeds suggested COL10A1 as a candidate for canine skeletal dysplasia. We report the sequencing of the exons and promoter region of the COL10A1 gene in dog breeds fixed for a specific type of skeletal dysplasia known as chondrodysplasia, breeds that segregate the skeletal dysplasia phenotype, and control dogs of normal stature. Thirteen single nucleotide polymorphisms (SNPs), one insertion, and two deletions, one of which introduces a premature stop codon and likely results in nonsense-mediated decay and the degradation of the mutant allele product, were identified in the coding region. There appear to be no causal relationships between the polymorphisms identified in this study and short stature in dogs. Although COL10A1 haploinsufficiency is an important cause of SMCD in humans, it does not seem to be responsible for the skeletal dysplasia phenotype in these dog breeds. In addition, homozygosity for the nonsense allele does not result in the observed canine skeletal dysplasia phenotype.

Y chromosome haplotype analysis in purebred dogs.

In order to evaluate the genetic structure of purebred dogs, six Y chromosome microsatellite markers were used to analyze DNA samples from 824 unrelated dogs from 50 recognized breeds. A relatively small number of haplotypes (67) were identified in this large sample set due to extensive sharing of haplotypes between breeds and low haplotype diversity within breeds. Fifteen breeds were characterized by a single Y chromosome haplotype. Breed-specific haplotypes were identified for 26 of the 50 breeds, and haplotype sharing between some breeds indicated a common history. A molecular variance analysis (AMOVA) demonstrated significant genetic variation across breeds (63.7%) and with geographic origin of the breeds (11.5%). A network analysis of the haplotypes revealed further relationships between the breeds as well as deep rooting of many of the breed-specific haplotypes, particularly among breeds of African origin.