Abstract：
This study investigated the dominant blue eyes (DBE) trait linked to hearing impairment and variable white spotting in Maine Coon cats. Fifty-eight animals descending from two different DBE lineages, the Dutch and the Topaz lines, were sampled. They comprised 48 cats from the Dutch bloodline, including 9 green-eyed and 31 blue-eyed cats, with some individuals exhibiting signs of deafness, and 8 stillborn kittens. Samples from the Topaz lineage included ten blue-eyed animals. A brainstem auditory evoked potential test (BAER) revealed a reduced to absent response to auditory stimuli and absent physiological waveforms in all of the eight examined DBE animals. We sequenced the genome of two affected cats from the Dutch line and searched for variants in 19 candidate genes for the human Waardenburg syndrome and pigmentary disorders. This search yielded nine private protein-changing candidate variants in the genes PAX3, EDN3, KIT, OCA2, SLC24A5, HERC2 and TYRP1. The genotype-phenotype co-segregation was observed for the PAX3 variant within all animals from the Dutch lineage. The mutant allele was absent from 461 control genomes and 241 additionally genotyped green-eyed Maine Coons. We considered the PAX3 variant as the most plausible candidate -a heterozygous nonsense single basepair substitution in exon 6 of PAX3 (NC_051841.1: g.205,787,310G>A, XM_019838731.3:c.937C>T, XP_019694290.1:p.Gln313*), predicted to result in a premature stop codon. PAX3 variants cause auditory-pigmentary syndrome in humans, horses, and mice. Together with the comparative data from other species, our findings strongly suggest PAX3:c.937C>T (OMIA:001688-9685) as the most likely candidate variant for the DBE, deafness and minimal white spotting in the Maine Coon Dutch line. Finally, we propose the designation of DBERE (Rociri Elvis Dominant Blue Eyes) allele in the domestic cat.
摘要：
这项研究调查了与缅因州Coon猫的听力障碍和可变的白色斑点有关的显性蓝眼睛（DBE）特征。58只动物来自两个不同的DBE谱系，荷兰人和黄玉线，被取样。它们包括48只来自荷兰血统的猫，包括9只绿眼猫和31只蓝眼猫，有些人表现出耳聋的迹象，和8只死产小猫.来自Topaz谱系的样品包括十只蓝眼睛的动物。脑干听觉诱发电位测试（BAER）显示，在所有八只接受检查的DBE动物中，对听觉刺激的反应降低至无反应，并且没有生理波形。我们对来自荷兰系的两只受影响的猫的基因组进行了测序，并在人类Waardenburg综合征和色素性疾病的19个候选基因中搜索了变体。该搜索在基因PAX3，EDN3，KIT，OCA2、SLC24A5、HERC2和TYRP1。在来自荷兰谱系的所有动物中观察到PAX3变体的基因型-表型共分离。461个对照基因组和241个另外的基因分型绿眼缅因州Coons中不存在突变等位基因。我们认为PAX3变体是最合理的候选者-PAX3外显子6中的杂合无义单碱基对取代（NC_051841.1：g.205,787,310G>A，XM_019838731.3:c.937C>T，XP_019694290.1:p.Gln313*),预测会导致过早的终止密码子。PAX3变异导致人类听觉色素性综合征，马,和老鼠。连同其他物种的比较数据，我们的发现强烈表明PAX3：c.937C>T（OMIA：001688-9685）是DBE最有可能的候选变体，缅因州库恩荷兰线的耳聋和最少的白色斑点。最后,我们建议在家猫中指定DBERE（RociriElvis显性蓝眼睛）等位基因。
