An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs

Science. 2009 Aug 21;325(5943):995-8. doi: 10.1126/science.1173275. Epub 2009 Jul 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breeding
  • Chondrocytes / metabolism
  • Dogs / anatomy & histology
  • Dogs / genetics*
  • Evolution, Molecular
  • Extremities / anatomy & histology*
  • Fibroblast Growth Factor 4 / genetics*
  • Gene Duplication*
  • Gene Expression Regulation*
  • Gene Frequency
  • Genes, Duplicate
  • Genome-Wide Association Study
  • Haplotypes
  • Humerus / metabolism
  • Long Interspersed Nucleotide Elements
  • Oligonucleotide Array Sequence Analysis
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Regulatory Sequences, Nucleic Acid
  • Retroelements / genetics*
  • Selection, Genetic

Substances

  • Fibroblast Growth Factor 4
  • Retroelements