Dominant blue eyes in Maine Coon cats: New PAX3 variant and updated phenotypic data.

Feline minimal white spotting associated with blue eyes, a trait called DBE by breeders for dominant blue eyes, was selected recently to create various lineages of cats and the Celestial breed. Previously, we identified three Paired Box 3 (PAX3) gene variants that account for some of the DBE phenotypes in cats, confirming different founding effects. Using a candidate gene approach, we identified a fourth PAX3 variant in a purebred Maine Coon lineage segregating for DBE and lacking a previously identified genomic variant. Segregation of the variant was consistent with the dominant inheritance pattern observed in this DBE lineage called the "Agostino line" by breeders. This PAX3:c.160del frameshift variant, located in PAX3 exon 2, was predicted to produce a truncated PAX3 protein: PAX3:p.(His54ThrTer108) that would lack 78% of the amino acids of the wildtype protein. All 13 DBE Maine Coon cats from the line were heterozygous for the variant, that was absent in all non-DBE Maine Coon cats from the line and in all control cat genomes (n > 300). We propose that this PAX3:c.160del variant represents the DBEAGO (Agostino Dominant Blue Eyes) allele in the domestic cat. In addition, we improved the phenotypic description of DBE in Maine Coon cats, highlighting the need to reassess the prevalence of deafness and revealing the existence of latent cats in the previously described DBERE (Rociri Elvis Dominant Blue Eyes) Maine Coon lineage.