<i>FGF4</i> retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29073074.
- Also identified by DOI 10.1073/pnas.1709082114 and PMC identifier 5664524.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (<i>P</i><sub>Bonferroni</sub> = 0.01) and intervertebral disc disease (IVDD) across breeds (<i>P</i><sub>Bonferroni</sub> = 4.0 × 10<sup>-10</sup>) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed <i>FGF4</i> retrogene within this shared region. The <i>FGF4</i> retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.
Medical subject headings
- Dog Diseases
- Fibroblast Growth Factor 4
- Intervertebral Disc Degeneration
- Intervertebral Disc Displacement
- Osteochondrodysplasias