title: A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs.
abstract: Coat color dilution in several breeds of dog is characterized by a specific pigmentation phenotype and sometimes accompanied by hair loss and recurrent skin inflammation, the so-called color dilution alopecia or black hair follicular dysplasia. Coat color dilution (d) is inherited as a Mendelian autosomal recessive trait. In a previous study, MLPH polymorphisms showed perfect cosegregation with the dilute phenotype within breeds. However, different dilute haplotypes were found in different breeds, and no single polymorphism was identified in the coding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5'-region of the canine MLPH gene and identified a strong candidate single nucleotide polymorphism within the nontranslated exon 1, which showed perfect association to the dilute phenotype in 65 dilute dogs from 7 different breeds. The A/G polymorphism is located at the last nucleotide of exon 1 and the mutant A-allele is predicted to reduce splicing efficiency 8-fold. An MLPH mRNA expression study using quantitative reverse transcriptase-polymerase chain reaction confirmed that dd animals had only about approximately 25% of the MLPH transcript compared with DD animals. These results provide preliminary evidence that the reported regulatory MLPH mutation might represent a causal mutation for coat color dilution in dogs.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Berne, Bremgartenstrasse 109a, 3001 Berne, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Ute
authors.initials: U
authors.lastname: Philipp
authors.forename: Bianca
authors.initials: B
authors.lastname: Haase
authors.forename: Anne-Rose
authors.initials: AR
authors.lastname: Günzel-Apel
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
mesh_terms: D000375:Aging / Q000235:genetics; D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004285:Dogs / Q000235:genetics*; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D006200:Hair Color / Q000235:genetics*; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins