Insertion and Evolution of an Endogenous Retrovirus into KIT is Responsible for Multiple Phenotypes at the White Locus in the Domestic Cat
Wallace, Andrea Brynne
Mount, Stephen M
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The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. I preformed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1), as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and White Spotting. The retrotransposition interrupts a DNase I hypersensitive site in KIT intron 1 that was previously demonstrated to regulate temporal and tissue specific expression of KIT in mice. A large population-genetic survey of cats (n=269), supports our findings and demonstrates statistical significance of the FERV1 LTR and full-length element with Dominant White (p < 0.0001) and White Spotting (p< 0.0001), respectively.