Additional PAX3 Variants for Dominant Blue Eyes in Cats

Since the recent publication of the first feline variant of the PAX3 (Paired Box 3) gene associated with blue eyes and minimal white spotting (DBE, Dominant Blue Eyes), three further variants of PAX3 have been reported in felines. However, these four variants do not account for all the different feline lines that exhibit DBE. Whole-genome sequencing using short-read and long-read technologies identified a large complex structural variant involving two deletions and an inversion in a purebred line of British shorthair and longhair cats. All 39 British cats with a BDE phenotype were heterozygous for the variant, that was absent in 47 non-DBE cats and 16 DBE cats from other breeding lines. The purebred British shorthair founder female named Nadeya was also heterozygous for the variant, and the segregation of the variant is consistent with dominant inheritance. We named this NC_058375.1:g.[205097674_207411974del;207411975_211290497inv;211290498_211387174del] variant the DBE^NAD (Nadeya Dominant Blue Eyes) allele. In addition, a candidate gene approach identified a nonsense variant, XM_019838731.3:c.784C>T, in the fifth exon of PAX3 in a second breeding line originating from a female named Marusya. The segregation of this nonsense variant is consistent with dominant inheritance, and a perfect genotype-phenotype correlation was observed in the 16 cats from this line, so we propose that this sixth variant of PAX3 represents the DBE^MARU (Marusya Dominant Blue Eyes) allele in the domestic cat. Our study has identified two further variants of the PAX3 gene associated with DBE in domestic cats, which will help to improve genotyping of the breeding stock.