title: An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs.
abstract: 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.
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Parker
authors.forename: Bridgett M
authors.initials: BM
authors.lastname: VonHoldt
authors.forename: Pascale
authors.initials: P
authors.lastname: Quignon
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Margulies
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shao
authors.forename: Dana S
authors.initials: DS
authors.lastname: Mosher
authors.forename: Tyrone C
authors.initials: TC
authors.lastname: Spady
authors.forename: Abdel
authors.initials: A
authors.lastname: Elkahloun
authors.forename: Michele
authors.initials: M
authors.lastname: Cargill
authors.forename: Paul G
authors.initials: PG
authors.lastname: Jones
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Maslen
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Acland
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Sutter
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kuroki
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: 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
chemical_list: D051519:Fibroblast Growth Factor 4; D018626:Retroelements