Journal of Heredity Advance Access published online on September 1, 2007
Journal of Heredity, doi:10.1093/jhered/esm072
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Four Independent Mutations in the Feline Fibroblast Growth Factor 5 Gene Determine the Long-Haired Phenotype in Domestic Cats
From the Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702 (Kehler, David, Bajema, O'Brien, and Menotti-Raymond); Center for Animal Transgenesis and Germ Cell Research, Room 102, Myrin Building, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348 (Kehler); Department of Health and Human Services, National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894 (Schäffer); Centro de Biologia Genômica e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS 90619-900, Brazil (Eizirik); Department of Otolaryngology and Neuroscience, 720 Rutland Avenue, Johns Hopkins University, Baltimore, MD 21205 (Ryugo); and Nestlé-Purina PetCare Company, St. Louis, MO 63134 (Hannah)
Address correspondence to J. S. Kehler at the address above, or e-mail: jkehler{at}ncifcrf.gov.
To determine the genetic regulation of "hair length" in the domestic cat, a whole-genome scan was performed in a multigenerational pedigree in which the "long-haired" phenotype was segregating. The 2 markers that demonstrated the greatest linkage to the long-haired trait (log of the odds 
6) flanked an estimated 10-Mb region on cat chromosome B1 containing the Fibroblast Growth Factor 5 (FGF5) gene, a candidate gene implicated in regulating hair follicle growth cycle in other species. Sequence analyses of FGF5 in 26 cat breeds and 2 pedigrees of nonbreed cats revealed 4 separate mutations predicted to disrupt the biological activity of the FGF5 protein. Pedigree analyses demonstrated that different combinations of paired mutant FGF5 alleles segregated with the long-haired phenotype in an autosomal recessive manner. Association analyses of more than 380 genotyped breed and nonbreed cats were consistent with mutations in the FGF5 gene causing the long-haired phenotype in an autosomal recessive manner. In combination, these genomic approaches demonstrated that FGF5 is the major genetic determinant of hair length in the domestic cat.
Corresponding Editor: Leif Andersson
Received March 19, 2007
Accepted July 11, 2007
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