Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats.
Bottom Line: B1) as the feline W locus.The retrotransposition interrupts a DNAase I hypersensitive site in KIT intron 1 that is highly conserved across mammals and was previously demonstrated to regulate temporal and tissue-specific expression of KIT in murine hematopoietic and melanocytic cells.A large-population genetic survey of cats (n = 270), representing 30 cat breeds, supports our findings and demonstrates statistical significance of the FERV1 LTR and full-length element with Dominant White/blue iris (P < 0.0001) and white spotting (P < 0.0001), respectively.
Affiliation: Laboratory of Genomic Diversity, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702.Show MeSH
Related in: MedlinePlus
Mentions: Three white spotted individuals in Pedigree 1 (03-138, 04-053, 04-054) (Figure 1) exhibited “” alleles for a W genotyping assay, demonstrating neither the presence of the W allele nor the wild-type (w) allele (Figure 3). Analysis of short tandem repeat profiles (Menotti-Raymond et al. 1997) confirmed their parentage (data not shown). Because their parents appeared to be homozygous for the LTR insertion, these spotted individuals posed contradictions of both phenotypic and genotypic expectations. Ultimately, utilizing long-range PCR methodology, we generated a 7333-bp PCR product from the three white spotted individuals spanning the site of the W allele and identified a full-length 7125 bp feline endogenous retroviral sequence. The sequence exhibited highest similarity to the FERV1 element ERV1-1_FCa-I (Anai et al. 2012) on chromosome D1, demonstrating 98.4% identity over a span of 6333 bp (Figure S1) (GenBank submission no. KC893344). The full-length FERV1 insertion element demonstrated identical sequence identity to the LTR insertion of the W allele (Figure S1).
Affiliation: Laboratory of Genomic Diversity, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702.