A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds
A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds
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DOI：
10.1111/age.12104
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发表时间：
2014-04-01
期刊：
影响因子：
2.4
通讯作者：
Dall'Olio, S.
中科院分区：
文献类型：
--
作者：
Fontanesi, L.;Scotti, E.;Dall'Olio, S.
在兔中，稀释基因座由隐性突变等位基因（d）决定，该等位基因导致真黑素和褐黑素色素的稀释。在小鼠中，类似的表型由肌球蛋白VA、Rab 27 a和黑素蛋白（MLPH）基因的突变决定。在这项研究中，我们调查了兔MLPH基因，并表明该基因中的突变似乎是该物种的稀毛色的原因。首先对分离黑色和灰色（稀释或蓝色）毛色的标记的Giant F1家族进行MLPH基因内含子1中复杂indel的基因分型，该内含子1与毛色表型完全相关（=0.00; LOD=4.82）。然后，我们对18只不同毛色的家兔（包括蓝色动物）的MLPH基因进行了6357 bp的测序。共发现165个多态性位点，其中137个位于非编码区，28个位于编码外显子。其中之一是外显子5的移码缺失。基因分型的半同胞家庭证实了这种突变与蓝色毛色的完全共分离。对23个品种的198只家兔进行了突变分析。所有蓝维也纳兔和其他品种的所有蓝/灰/灰兔（加利福尼亚兔、蓖麻雷克斯兔、红毛巨兔、英国斑点兔、仙女马尔堡兔和仙女珍珠兔）均为该缺失纯合子。MLPH基因在兔中的鉴定为稀染位点的致病基因，为研究该基因在色素沉着中的作用提供了一个新的突变体，并为人类Griscelli综合征3型提供了一个天然的动物模型。
In rabbit, the dilute locus is determined by a recessive mutated allele (d) that causes the dilution of both eumelanic and pheomelanic pigmentations. In mice, similar phenotypes are determined by mutations in the myosin VA, Rab27a and melanophilin (MLPH) genes. In this study, we investigated the rabbit MLPH gene and showed that a mutation in this gene appears responsible for the dilute coat colour in this species. Checkered Giant F1 families segregating for black and grey (diluted or blue) coat colour were first genotyped for a complex indel in intron 1 of the MLPH gene that was completely associated with the coat colour phenotype (=0.00; LOD=4.82). Then, we sequenced 6357bp of the MLPH gene in 18 rabbits of different coat colours, including blue animals. A total of 165 polymorphisms were identified: 137 were in non-coding regions and 28 were in coding exons. One of them was a frameshift deletion in exon 5. Genotyping the half-sib families confirmed the complete cosegregation of this mutation with the blue coat colour. The mutation was analysed in 198 rabbits of 23 breeds. All Blue Vienna and all other blue/grey/ash rabbits in other breeds (Californian, Castor Rex, Checkered Giant, English Spot, Fairy Marburg and Fairy Pearly) were homozygous for this deletion. The identification of MLPH as the responsible gene for the dilute locus in rabbit provides a natural animal model for human Griscelli syndrome type 3 and a new mutant to study the role of this gene on pigmentation.