Complex intragene deletion leads to oculocutaneous albinism in tanuki (Japanese raccoon dog)
Complex intragene deletion leads to oculocutaneous albinism in tanuki (Japanese raccoon dog)
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复杂的基因内缺失导致狸猫（日本貉）眼皮肤白化病
DOI：
10.1139/gen-2020-0049
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发表时间：
2020
期刊：
影响因子：
3.1
通讯作者：
Koga Akihiko
中科院分区：
文献类型：
--
作者：
Mae Yuji;Nagara Kenji;Miyazaki Manabu;Katsura Yukako;Enomoto Yuki;Koga Akihiko
Tanuki（Nyctereutes procyonoides viverrinus），或日本浣熊狗，是一种原产于日本的犬。阿狸完全眼皮肤白化病是比较常见的在山区的日本大陆。酪氨酸酶（Tyrosinase）是由酪氨酸酶（Tyr）基因编码的一种酶，是黑色素生物合成所必需的酶。我们检测了一只白化病狸猫的TYR基因的结构和核苷酸序列，发现第三个外显子由于约11 kb的缺失而被去除。此外，在第五外显子中发现了两个非同义核苷酸替换。这些突变是白化病表型的可能原因;然而，发生的顺序尚不清楚。即使11-kb缺失不是这些突变中的第一个，也认为它导致酪氨酸酶功能的完全丧失，因为第三外显子携带酪氨酸酶的两个铜结合位点之一的密码子，并且这些位点对于酶功能是必需的。有趣的是，这种缺失并不是简单地去除一个11 kb的片段：一个内部部分被保留为反向的片段。我们提出了这种突变可能的形成过程，涉及多个DNA断裂事件，或倒置后删除。
Tanuki (Nyctereutes procyonoides viverrinus), or Japanese raccoon dog, is a canine native to Japan. Tanuki with complete oculocutaneous albinism are relatively frequent in mountainous areas of mainland Japan. Tyrosinase, which is encoded by theTYRgene, is an enzyme essential for the biosynthesis of melanin pigment. We examined the structure and nucleotide sequence ofTYRin an albino tanuki and found that the third exon was removed due to a deletion of approximately 11 kb. In addition, two nonsynonymous nucleotide substitutions were found in the fifth exon. These mutations are possible causes of the albino phenotype; however, the order of occurrence is unclear. Even if the 11-kb deletion was not the first of these mutations, it is considered to cause a total loss of the tyrosinase function because the third exon carries codons for one of the two copper-binding sites of tyrosinase and these sites are essential for the enzyme function. Intriguingly, the deletion was not a simple removal of an 11-kb segment: an internal portion was retained as a segment in the reverse orientation. We propose possible formation processes for this mutation that involve multiple DNA scission events, or an inversion followed by a deletion.