title: Four independent mutations in the feline fibroblast growth factor 5 gene determine the long-haired phenotype in domestic cats.
abstract: 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 > or = 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.
authors.affiliation: The Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702, USA. jkehler@ncifcrf.gov
authors.forename: James S
authors.initials: JS
authors.lastname: Kehler
authors.forename: Victor A
authors.initials: VA
authors.lastname: David
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Kristina
authors.initials: K
authors.lastname: Bajema
authors.forename: Eduardo
authors.initials: E
authors.lastname: Eizirik
authors.forename: David K
authors.initials: DK
authors.lastname: Ryugo
authors.forename: Steven S
authors.initials: SS
authors.lastname: Hannah
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Marilyn
authors.initials: M
authors.lastname: Menotti-Raymond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D051521:Fibroblast Growth Factor 5 / Q000235:genetics*; D005819:Genetic Markers; D016678:Genome; D006197:Hair / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013045:Species Specificity
chemical_list: D005819:Genetic Markers; D051521:Fibroblast Growth Factor 5