A Simple Repeat Polymorphism in the MITF-M Promoter Is a Key Regulator of White Spotting in Dogs

摘要: The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. phenotypic effects of four S alleles range from solid colour to extreme (s(w)). We have investigated candidate mutations associated s(w) allele, a SINE insertion, SNP at conserved site and simple repeat polymorphism all MITF-M promoter as well 12 base pair deletion exon 1B. variants loci were also found among wolves we conclude that none these could be sole causal mutation, least not for spotting. propose three canine are caused by independent but represent haplotype due different combinations polymorphisms. showed extensive diversity both wolves, allele-sharing was common between spotted non-existent dogs. This finding unexpected Solid assumed wild-type allele. data indicate has been target selection during dog domestication breed formation. evaluated significance polymorphisms Luciferase assay, conclusive evidence affects activity. Three gave consistently lower activity compared allele colour. cooperativity factors binding on either flanking sides repeat. Thus, genetic functional show key regulator