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.

中文翻译：

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Celestial 品种和某些蓝眼猫科动物育种系中插入了 PAX3

在过去的 60 年里，家养远交猫的许多遗传性状被选择并保留，从而诞生了以单一皮毛或形态表型为特征的新品种。其中，猫科动物饲养员选择了与蓝眼睛相关的最小白斑来培育阿尔泰、黄玉和天体品种。各种已建立的品种也在其血统中引入了这一特征。该性状经育种数据证实为常染色体显性遗传，首次在哈萨克斯坦和俄罗斯的家猫、俄罗斯的英国短毛猫和英国长毛猫以及荷兰的缅因猫中被描述，这表明了不同的创始效应。通过全基因组关联研究，我们确定了 C1 染色体上的一个区域，该区域与法国天神品种中最小的白斑和蓝眼睛表型（也被育种者称为 DBE 为显性蓝眼睛）相关。在该区域内我们确定了配对盒3（帕克斯3）作为最强的候选基因，因为帕克斯3是一个关键的监管者麻省理工学院（中号黑色素细胞-我诱导 时间转录 F演员） 和帕克斯3先前已在各种具有或不具有蓝眼睛的具有白色斑点的物种中发现了变异，包括老鼠和马。天猫的全基因组测序揭示了内源性逆转录病毒 LTR（长末端重复）插入帕克斯3已知内含子 4 含有调控序列（保守非编码元件 [CNE]），参与帕克斯3表达。该插入位于 CNE2 和 CNE3 附近。所有 52 只具有 DBE 表型的 Celestial 猫和 Celestial 混种猫都出现了这种插入，而在它们的 22 只非 DBE 同窝猫和来自不同品种的 87 只非 DBE 猫中则没有这种插入。远交的 Celestial 创始人对于插入也是杂合的。此外，在与 Celestial 创始人有关的 9 只 DBE 缅因猫和 4 只起源不确定的 DBE 西伯利亚猫中也发现了这种变异。天体品种中该变异的分离与显性遗传一致，并且似乎与耳聋无关。我们建议这个 NC_018730.3:g.206974029_206974030insN[395] 变体代表DBE西尔（天主蓝眼) 家猫的等位基因。