Abstract：
During the last 60 years many inherited traits in domestic outbred cats were selected and retained giving birth to new breeds characterised by singular coat or morphological phenotypes. Among them, minimal white spotting associated with blue eyes was selected by feline breeders to create the Altai, Topaz, and Celestial breeds. Various established breeds also introduced this trait in their lineages. The trait, that was confirmed as autosomal dominant by breeding data, was first described in domestic cats from Kazakhstan and Russia, in British shorthair and British longhair from Russia, and in Maine Coon cats from the Netherlands, suggesting different founding effects. Using a genome-wide association study we identified a single region on chromosome C1 that was associated with the minimal white spotting and blue eyes phenotype (also called DBE by breeders for dominant blue eyes) in the French Celestial breed. Within that region we identified Paired Box 3 (PAX3) as the strongest candidate gene, since PAX3 is a key regulator of MITF (Melanocyte-Inducing Transcription Factor) and PAX3 variants have been previously identified in various species showing white spotting with or without blue eyes including the mouse and the horse. Whole genome sequencing of a Celestial cat revealed an endogenous retrovirus LTR (long terminal repeat) insertion within PAX3 intron 4 known to contain regulatory sequences (conserved non-coding element [CNE]) involved in PAX3 expression. The insertion is in the vicinity of CNE2 and CNE3. All 52 Celestial and Celestial-mixed cats with a DBE phenotype presented the insertion, that was absent in their 22 non-DBE littermates and in 87 non-DBE cats from various breeds. The outbred Celestial founder was also heterozygous for the insertion. Additionally, the variant was found in nine DBE Maine Coon cats related to the Celestial founder and four DBE Siberian cats with an uncertain origin. Segregation of the variant in the Celestial breed is consistent with dominant inheritance and does not appear to be associated with deafness. We propose that this NC_018730.3:g.206974029_206974030insN[395] variant represents the DBECEL (Celestial Dominant Blue Eyes) allele in the domestic cat.
摘要：
在过去的60年中，选择并保留了家养近交猫的许多遗传特征，从而生出了以奇异皮毛或形态表型为特征的新品种。其中,猫科动物选择与蓝眼睛相关的最小白色斑点来创建阿尔泰，黄玉,和天体品种。各种成熟的品种也在其谱系中引入了这种特征。的特点，这被育种数据证实为常染色体显性遗传，最初是在哈萨克斯坦和俄罗斯的家猫中描述的，来自俄罗斯的英国短毛线和英国长毛，在缅因州，来自荷兰的库恩猫，暗示不同的创始效应。使用全基因组关联研究，我们确定了C1染色体上的一个区域，该区域与法国天体品种中最小的白色斑点和蓝眼睛表型（也被显性蓝眼睛的育种者称为DBE）相关。在该区域内，我们将配对框3（PAX3）确定为最强的候选基因，因为PAX3是MITF(黑色素细胞诱导转录因子)的关键调节因子,并且先前已经在包括小鼠和马在内的各种物种中鉴定出PAX3变体,其显示有或没有蓝眼睛的白色斑点。天猫的全基因组测序揭示了PAX3内含子4内的内源性逆转录病毒LTR（长末端重复序列）插入，已知其包含与PAX3表达有关的调节序列（保守的非编码元件[CNE]）。插入在CNE2和CNE3附近。所有52只具有DBE表型的天体和天体混合猫都出现了插入，这在他们的22名非DBE同窝猫和来自各种品种的87名非DBE猫中都没有。远亲的天体创始人也是杂合的。此外,该变体在与天体创始人有关的9只DBE缅因州Coon猫和4只来源不确定的DBE西伯利亚猫中发现。天体品种中变体的分离与显性遗传一致，似乎与耳聋无关。我们建议此NC_018730.3：g.206974029_206974030insN[395]变体代表家猫中的DBECEL（天体优势蓝眼睛）等位基因。
