PT  - JOURNAL ARTICLE
AU  - Emily A. Brown
AU  - Peter J. Dickinson
AU  - Tamer Mansour
AU  - Beverly K. Sturges
AU  - Miriam Aguilar
AU  - Amy E. Young
AU  - Courtney Korff
AU  - Jenna Lind
AU  - Cassandra L. Ettinger
AU  - Samuel Varon
AU  - Rachel Pollard
AU  - C. Titus Brown
AU  - Terje Raudsepp
AU  - Danika L. Bannasch
TI  - <em>FGF4</em> retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs
AID  - 10.1101/144022
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 144022
4099  - http://biorxiv.org/content/early/2017/05/30/144022.short
4100  - http://biorxiv.org/content/early/2017/05/30/144022.full
AB  - 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 (pBonferroni=0.0072) and intervertebral disc disease (IVDD) across breeds (pBonferroni=4.02×10−10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 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.