title: Variant in the RFWD3 gene associated with PATN1, a modifier of leopard complex spotting.
abstract: Leopard complex spotting (LP), the result of an incompletely dominant mutation in TRPM1, produces a collection of unique depigmentation patterns in the horse. Although the LP mutation allows for expression of the various patterns, other loci are responsible for modification of the extent of white. Pedigree analysis of families segregating for high levels of patterning indicated a single dominant gene, named Pattern-1 (PATN1), as a major modifier of LP. Linkage analysis in two half-sibling families segregating for PATN1 identified a 15-Mb region on ECA3p that warranted further investigation. Whole transcriptome sequencing of skin samples from horses with and without the PATN1 allele was performed to identify genic SNPs for fine mapping. Two Sequenom assays were utilized to genotype 192 individuals from five LP-carrying breeds. The initial panel highlighted a 1.6-Mb region without a clear candidate gene. In the second round of fine mapping, SNP ECA3:23 658 447T>G in the 3'-UTR of RING finger and WD repeat domain 3 (RFWD3) reached a significance level of P = 1.063 × 10(-39). Sequencing of RFWD3 did not identify any coding polymorphisms specific to PATN1 horses. Genotyping of the RFWD3 3'-UTR SNP in 54 additional LP animals and 327 horses from nine breeds not segregating for LP further supported the association (P = 4.17 × 10(-115)). This variant is a strong candidate for PATN1 and may be particularly useful for LP breeders to select for high levels of white patterning.
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Holl
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Brooks
authors.affiliation: Quill Lake, SK, S0A3E0, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Archer
authors.affiliation: Department of Biology, University of Tampa, Tampa, FL, 33606, USA.
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.affiliation: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: J
authors.initials: J
authors.lastname: Malvick
authors.affiliation: Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: M C T
authors.initials: MC
authors.lastname: Penedo
authors.affiliation: Department of Population Health and Reproduction, Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Bellone
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001947:Breeding; D002874:Chromosome Mapping; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006200:Hair Color / Q000235:genetics*; D006736:Horses / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D044767:Ubiquitin-Protein Ligases
keywords: equine; pigmentation; white spotting