An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs.
Retrotransposition of processed mRNAs is a common source of novel sequence acquired during the evolution of genomes. Although the vast majority of retroposed gene copies, or retrogenes, rapidly accumulate debilitating mutations that disrupt the reading frame, a small percentage become new genes that encode functional proteins. By using a multibreed association analysis in the domestic dog, we demonstrate that expression of a recently acquired retrogene encoding fibroblast growth factor 4 (fgf4) is strongly associated with chondrodysplasia, a short-legged phenotype that defines at least 19 dog breeds including dachshund, corgi, and basset hound. These results illustrate the important role of a single evolutionary event in constraining and directing phenotypic diversity in the domestic dog.
Parker
Heidi G
HG
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
VonHoldt
Bridgett M
BM
Quignon
Pascale
P
Margulies
Elliott H
EH
Shao
Stephanie
S
Mosher
Dana S
DS
Spady
Tyrone C
TC
Elkahloun
Abdel
A
Cargill
Michele
M
Jones
Paul G
PG
Maslen
Cheryl L
CL
Acland
Gregory M
GM
Sutter
Nathan B
NB
Kuroki
Keiichi
K
Bustamante
Carlos D
CD
Wayne
Robert K
RK
Ostrander
Elaine A
EA
D000818:Animals; D001947:Breeding; D019902:Chondrocytes / Q000378:metabolism; D004285:Dogs / Q000033:anatomy & histology / Q000235:genetics*; D019143:Evolution, Molecular; D005121:Extremities / Q000033:anatomy & histology*; D051519:Fibroblast Growth Factor 4 / Q000235:genetics*; D020440:Gene Duplication; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020131:Genes, Duplicate; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006811:Humerus / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid; D018626:Retroelements / Q000235:genetics*; D012641:Selection, Genetic
D051519:Fibroblast Growth Factor 4; D018626:Retroelements