Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients in Japan indicate that three polymorphic sequences in the tyrosinase gene promoter could be powerful markers for indirect gene diagnosis
Polymorphic sequences of the tyrosinase gene: allele analysis on 16 OCA1 patients in Japan indicate that three polymorphic sequences in the tyrosinase gene promoter could be powerful markers for indirect gene diagnosis
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DOI：
10.1007/s10038-002-8648-3
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Tomita, Y
中科院分区：
文献类型：
--
作者：
Tanita, M;Matsunaga, J;Tomita, Y
自1989年以来，已有大量酪氨酸酶基因突变导致眼皮肤白化病（OCA）的报道。然而，大约 15% 的酪氨酸酶相关 OCA (OCA1) 杂合子患者携带未表征的突变，该突变可能存在于酪氨酸酶基因的常规检查区域之外。在这种情况下，酪氨酸酶基因的多态性序列可能有助于鉴定 OCA1 等位基因。在这项研究中，我们检查了 16 名 OCA1 患者、他们的亲属以及 108 名正常色素的日本人的酪氨酸酶基因的 4 个多态性序列。结果显示，启动子区-800至-900处有7个不同长度的复杂二核苷酸重复序列，内含子2的3'端有3个不同长度的多胸苷序列。对启动子区-301 (C/T)和-199 (C/A)两个多态性序列进行聚合酶链反应-限制性片段长度多态性分析，使我们将酪氨酸酶基因分为三组。利用这些多态性序列，我们可以在超过 80% 的父母基因组 DNA 可用的病例中识别出 OCA1 等位基因。酪氨酸酶基因启动子中的三个多态性序列对于此目的特别有用。
Since 1989, a large number of mutations of the tyrosinase gene, which result in oculocutaneous albinism (OCA), have been reported. However, approximately 15% of patients with tyrosinase-related OCA (OCA1) heterozygously carried an uncharacterized mutation, which presumably existed outside of the ordinarily examined area of the tyrosinase gene. In such cases, polymorphic sequence(s) of the tyrosinase gene might be useful to identify the OCA1 allele. In this study, we examined four polymorphic sequences of the tyrosinase gene in 16 patients with OCA1, their relatives, and 108 normally pigmented Japanese individuals. The results showed a complex dinucleotide repeat in the promoter region at -800 to -900 of seven different lengths, and a polythymidine sequence in the 3' end of intron 2 of three different lengths. Polymerase chain reaction-restriction fragment length polymorphism analysis of two polymorphic sequences at -301 (C/T) and -199 (C/A) in the promoter region allows us to classify the tyrosinase gene into three groups. Using these polymorphic sequences, we could identify the OCA1 allele in more than 80% of cases in which the parents' genomic DNA was available. Three polymorphic sequences in the tyrosinase gene promoter are particularly useful for this purpose.