RT Journal Article
SR Electronic
T1 <em>FGF4</em> retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 144022
DO 10.1101/144022
A1 Emily A. Brown
A1 Peter J. Dickinson
A1 Tamer Mansour
A1 Beverly K. Sturges
A1 Miriam Aguilar
A1 Amy E. Young
A1 Courtney Korff
A1 Jenna Lind
A1 Cassandra L. Ettinger
A1 Samuel Varon
A1 Rachel Pollard
A1 C. Titus Brown
A1 Terje Raudsepp
A1 Danika L. Bannasch
YR 2017
UL http://biorxiv.org/content/early/2017/05/30/144022.abstract
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.