Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits
Molecular analysis of common polymorphisms within the human Tyrosinase locus and genetic association with pigmentation traits
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DOI：
10.1111/pcmr.12253
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发表时间：
2014-07-01
影响因子：
4.3
通讯作者：
Sturm, Richard A.
中科院分区：
文献类型：
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作者：
Jagirdar, Kasturee;Smit, Darren J.;Sturm, Richard A.
我们比较了培养的黑素细胞携带两个常见的TYR等位基因作为纯合192 S-402 R野生型，杂合和纯合变体的黑素生成活性。这包括TYR蛋白、DOPA氧化酶活性、糖基化和蛋白质的温度敏感性以及DOPA氧化酶水平的测定。纯合野生型菌株的平均水平较高的TYR蛋白和酶活性比其他基因型。纯合子402 Q/Q黑素细胞产生显著较少的TYR蛋白，显示改变的运输和糖基化，减少DOPA氧化酶。然而，接近野生型TYR活性水平可以在较低的生长温度下恢复。在来自昆士兰州东南部的样本人群中，这两种多态性存在于四种TYR单倍型上，指定为WT 192 S-402 R、192 Y-402 R和192 S-402 Q，其中双变体192 Y-402 Q的频率较低，为1.9%。基于细胞培养结果和单倍型关联，我们使用了一个加性模型来评估从这些单倍型的组合中衍生的十种可能的TYR基因型的多态性。
We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild-type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild-type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R and 192S-402Q with a double-variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes.