Browsing by Subject "endochondral ossification"

Chondrodysplasia is a disease caused by defects in endochondral ossification. Chondrodysplasia affects the growth of long bones and causes disproportionate dwarfism. In addition to humans, chondrodysplasia has been discovered from multiple dog breeds. Chondrodysplasia in Alaskan Malamutes has been discovered already in the 1970s, but the genetic background of the disease is still unknown. This master’s thesis was conducted in Professor Hannes Lohi’s research group. The aim of this thesis was to identify a locus associated with chondrodysplasia in Alaskan Malamutes, and to find and validate candidate variants. All samples used in this study were collected from private owners with their consent. The study cohort consisted of four families of Alaskan Malamutes with affected individuals. Data used in the study included genotype data, and data from whole exome and whole genome sequencing. A significant locus on chromosome 8 was discovered, using genome-wide association study. However, some of the families with affected Alaskan Malamutes did not share this locus. A candidate variant in GALNT16 was identified by filtering NGS data from the families sharing the risk locus. Validation of the candidate variant showed that the variant was not causative for chondrodysplasia in Alaskan Malamutes. Based on the results, it can be possible that the causative variant for chondrodysplasia in all affected Alaskan Malamutes is not the same, and chondrodysplasia in Alaskan Malamutes may be more heterogonous than previously thought.