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ReportsAn 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.
1 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2 Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA. 3 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. 4 Affymetrix Corporation, 3420 Central Expressway, Santa Clara, CA 95051, USA. 5 The WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicestershire LE14 4RT, UK. 6 Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 7 Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853, USA. 8 College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. 9 Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211, USA. 10 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA. * Present address: Genetics Navigenics, Foster City, CA 94404, USA.
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To whom correspondence should be addressed. E-mail: Science. ISSN 0036-8075 (print), 1095-9203 (online)
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