Assessment of collagen genes involved in fragmented medial coronoid process development in Labrador Retrievers as determined by affected sibling-pair analysis

OBJECTIVE: To evaluate the involvement of various collagen genes in the development of fragmented medial coronoid process (FCP) in Labrador Retrievers. SAMPLE POPULATION: 93 dogs originating from 13 litters were used in the study; FCP was diagnosed in 35 dogs, and each affected dog had at least 1 sibling that was also affected. Twelve dams and sires were included in the analysis. All dogs were purebred Labrador Retrievers except for 2 litters (offspring of a female Golden Retriever-Labrador Retriever mixed-breed dog). PROCEDURES: For each dog, DNA was isolated from blood samples. Polymorphic microsatellite markers adjacent to 14 candidate genes (ie, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A3, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, and COL24A1) were analyzed by use of PCR assays; genotypes were determined via automated detection of DNA products. The level of allele sharing between pairs of affected siblings was assessed. RESULTS: Among the 93 dogs, allele sharing of the 14 collagen genes was determined as follows: COL1A1, 45%; COL1A2, 47%; COL2A1, 37%; COL3A1, 32%; COL5A1, 43%; COL5A2, 32%; COL6A3, 36%; COL9A1, 45%; COL9A2, 49%; COL9A3, 38%; COL10A1, 46%; COL11A1, 52%; COL11A2, 47%; and COL24A1, 47%. CONCLUSIONS AND CLINICAL RELEVANCE: Because siblings share 50% of their genome at random, the fact that the percentages of allele sharing among the analyzed collagen genes were not significantly > 50% indicates that these genes are not determinant candidates for FCP in Labrador Retrievers. The gene for the vitamin D receptor could also be excluded because of its proximity to COL2A1.     

Evaluation of candidate genes as a cause of chondrodysplasia in Labrador retrievers

Chondrodysplasia (CD) is a disabling, hereditary disease in Labradors with short limbs, warranting genetic screening in families at risk. Segregation analysis of eight litters with 13 affected dogs showed that autosomal recessive inheritance was consistent with the observed incidence of CD in the litters. Possible involvement of eight candidate collagen genes (COL9A1, COL9A2, COL9A3, COMP, MATN3, COL2A1, COL11A1 and COL11A2) and of a sulfate transporter glycoprotein (SLC26A2) gene in eight affected dogs and in 14 related control Labradors was investigated. Assuming recessive inheritance, the candidate genes could not be implicated in CD.