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

Heidi G. Parker, Bridgett M. VonHoldt, Pascale Quignon, Elliott H. Margulies, Stephanie Shao, Dana S. Mosher, Tyrone C. Spady, Abdel Elkahloun, Michele Cargill, Paul G. Jones, Cheryl Maslen, Gregory M. Acland, Nathan B. Sutter, Keiichi Kuroki, Carlos D. Bustamante, Robert K. Wayne, Elaine A. Ostrander

    Research output: Contribution to journalArticle

    173 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)995-998
    Number of pages4
    JournalScience
    Volume325
    Issue number5943
    DOIs
    StatePublished - 2009

    Fingerprint

    Fibroblast Growth Factor 4
    Enchondromatosis
    Dogs
    Reading Frames
    Genes
    Genome
    Phenotype
    Messenger RNA
    Mutation
    Proteins

    ASJC Scopus subject areas

    • General

    Cite this

    Parker, H. G., VonHoldt, B. M., Quignon, P., Margulies, E. H., Shao, S., Mosher, D. S., ... Ostrander, E. A. (2009). An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science, 325(5943), 995-998. https://doi.org/10.1126/science.1173275

    An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. / Parker, Heidi G.; VonHoldt, Bridgett M.; Quignon, Pascale; Margulies, Elliott H.; Shao, Stephanie; Mosher, Dana S.; Spady, Tyrone C.; Elkahloun, Abdel; Cargill, Michele; Jones, Paul G.; Maslen, Cheryl; Acland, Gregory M.; Sutter, Nathan B.; Kuroki, Keiichi; Bustamante, Carlos D.; Wayne, Robert K.; Ostrander, Elaine A.

    In: Science, Vol. 325, No. 5943, 2009, p. 995-998.

    Research output: Contribution to journalArticle

    Parker, HG, VonHoldt, BM, Quignon, P, Margulies, EH, Shao, S, Mosher, DS, Spady, TC, Elkahloun, A, Cargill, M, Jones, PG, Maslen, C, Acland, GM, Sutter, NB, Kuroki, K, Bustamante, CD, Wayne, RK & Ostrander, EA 2009, 'An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs', Science, vol. 325, no. 5943, pp. 995-998. https://doi.org/10.1126/science.1173275
    Parker HG, VonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS et al. An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science. 2009;325(5943):995-998. https://doi.org/10.1126/science.1173275
    Parker, Heidi G. ; VonHoldt, Bridgett M. ; Quignon, Pascale ; Margulies, Elliott H. ; Shao, Stephanie ; Mosher, Dana S. ; Spady, Tyrone C. ; Elkahloun, Abdel ; Cargill, Michele ; Jones, Paul G. ; Maslen, Cheryl ; Acland, Gregory M. ; Sutter, Nathan B. ; Kuroki, Keiichi ; Bustamante, Carlos D. ; Wayne, Robert K. ; Ostrander, Elaine A. / An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. In: Science. 2009 ; Vol. 325, No. 5943. pp. 995-998.
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    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.",
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    AU - Margulies, Elliott H.

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    AU - Mosher, Dana S.

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    AU - Cargill, Michele

    AU - Jones, Paul G.

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