Abstract

Disrupting mutations affecting the tyrosinase (TYR) gene cause different forms of albinism in mice, humans and several other mammals. Classical genetic studies have already reported five alleles at the European rabbit Albino locus, indicated to be part of the C series, each of them with different actions on pheomelanin and eumelanin production, as well as on the eye colour. A few of these alleles have been already characterised at the DNA level by sequencing the coding region of the TYR gene in few rabbit breeds or strains with specific alleles at this locus. In this study, we further characterised the TYR gene by sequencing all coding and flanking regions in a total of 25 rabbits from 11 domestic breeds (Belgian Hare, Burgundy Fawn, Californian, Champagne d’Argent, Giant Chinchilla, Giant Grey, Havana, Leprino di Viterbo, New Zealand White, Silver and White Vienna) and in 11 wild rabbits from Sardinia. Sequencing data identified a total of 15 polymorphisms. We confirmed five missense mutations already detected by other authors, three of which associated with different coat colour phenotypes: p.T373K determining the albino allele; p.E294G causing the Himalayan and the chinchilla alleles; p.T358I observed only in Chinchilla rabbits. In addition to seven other synonymous mutations and one polymorphism in the 3’-untranslated region, two novel missense mutations were identified (p.T144S and p.K224T, the latest was detected only in wild rabbits). This study further contributed to disclose variability in the rabbit TYR gene and confirmed the effects on coat colours of missense mutations.

• Highlights

• Mutations in the tyrosinase (TYR) gene cause several coat colour alleles at the Albino locus in mammals.

• The TYR gene was sequenced in 11 domestic rabbit breeds and in a wild rabbit population.

• Fifteen single nucleotide polymorphisms (SNPs) were identified: seven were missense mutations.

• In silico analyses and information already available predicted the effects of some SNPs on coat colour.

• This study further contributed to disclose variability in the rabbit TYR gene.

摘要

影响酪氨酸酶（TYR）基因的破坏性突变在小鼠，人类和其他几种哺乳动物中引起不同形式的白化病。古典遗传学研究已经报告了欧洲兔子白化病基因座上的五个等位基因，这些基因被认为是C系列的一部分，每个等位基因对苯丙氨酸和金黄色素的产生以及眼睛的颜色都有不同的作用。通过在少数兔子品种或品系中具有特定等位基因的TYR基因的编码区测序，已经在DNA水平上表征了这些等位基因中的一些。在这项研究中，我们进一步表征了TYR通过对来自11个国内品种（比利时野兔，勃艮第小鹿，加利福尼亚州，香槟，阿肯特，大龙猫，大灰狗，哈瓦那，勒普里诺·迪维泰博，新西兰白，银和白色维也纳）和撒丁岛的11只野兔。测序数据共鉴定出15种多态性。我们确认了其他作者已经检测到的五个错义突变，其中三个与不同的毛色表型有关：p.T373K确定白化病等位基因；p.E294G引起喜马拉雅和黄鼠等位基因；p.T358I仅在龙猫兔子中观察到。除了3个非翻译区中的其他7个同义突变和1个多态性之外，还鉴定了2个新的错义突变（p.T144S和p.K224T，仅在野兔中检测到最新的）。TYR基因并证实了错义突变对毛色的影响。

• 强调

• 酪氨酸酶（TYR）基因的突变会在哺乳动物的白化病基因位点引起几个毛色等位基因。

• 该TYR基因在11个家兔品种和野生兔人口测序。

• 鉴定出15个单核苷酸多态性（SNP）：7个为错义突变。

• 在计算机分析中，已经获得的信息预测了某些SNP对外套颜色的影响。

• 这项研究进一步有助于揭示兔TYR基因的变异性。