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As to the orgin of the disease-causing gene of the Japanese-type adenine phosphoribosyltransferase deficiency

关于日本型腺嘌呤磷酸核糖转移酶缺乏症的致病基因的来源

基本信息

批准号：
61480484
负责人：
KAMATANI Naoyuki
金额：
$ 4.48万
依托单位：
Institute of Rheumatology, Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disease characterized by reccurrent urolithiatic episodes and renal insufficiency. This disease is especially common among Japanese at least partially because Japanese, as an ethnical group, have a special type of the disease designated as "the Japanese-type APRT deficiency" as we havev previously clarified. The original aim of the present project to clarify the origin of the disease-causing gene of the Japanese-type APRT deficiency has almost completely achieved. Thus, we have identified the gene responsible for this disease (APRT*J), identidied a nucleotide substitution in this gene (in exon 5), and also identified an amino acid substitution in the Japanese-type APRT enzyme (Met to Thr at position 136). Furthermore, we confirmed that this nucleotide and amino acid substitution are present in all the separate families with the Japanese-type APRT deficiency. We have devised a new diagnostic method identifying the amono ac … More id substitution seen in the Japanese-type mutant enzyme. In addition to the mutation specific for the Japanese-type APRT deficiency, we found a nucleotide substitution in intron 2. Based on the data about this restriction fragment length polymorphism, we provided confidential evidence that the disease-causing genes in separate families with the Japanese-type APRT deficiency derived from a sngle ancestor gene which was created in an ancestor of Japanese. Besides the orginal aim of the present project, we have been able to obtain some valuable results. First, we have diagnosed more than half of all the patients with APRT deficiency in the world. Second, we found that as much as 80% of all the families with APRT deficiency in Japan were classified as the Japanese-type. Therefore, the fact that APRT deficiency is especially common among Japanese is, at least in part, explained by the wide distribution of this mutant gene (APRT*J) among Japanese (but not among Caucacians). Third, we found most of the patients with APRT deficiency had not been properly diagnosed, and our report as to this disease will be benificial to many patients with this disease. We confirm that the evidence for a common ancestor disease-causing gene for as much as 80% of all the patients with a single disease in an ethnical group will affect thories of evolution, and will be against the concept of eugenics that has affected even laws of many modern countries. Less

腺嘌呤磷酸核糖基转移酶(APRT)缺乏症是一种以复发性尿路结石发作和肾功能不全为特征的遗传性疾病。这种疾病在日本人中特别常见，至少部分是因为日本人作为一个种族群体，有一种特殊的疾病类型，我们前面已经澄清过，这种疾病被称为“日本型aprt缺乏症”。本项目最初的目的是阐明日本型aprt缺乏症致病基因的来源，现在几乎完全实现了。因此，我们鉴定了该疾病的致病基因(aprt*J)，鉴定了该基因的核苷酸替换(外显子5)，还鉴定了日本型aprt酶(第136位Met to Thr)的氨基酸替换。此外，我们还证实了这种核苷酸和氨基酸的替换存在于所有日本型APRT缺乏症的家系中。我们设计了一种新的诊断方法来识别Amono ac…在日式突变酶中可以看到更多的id替代。除了日本型APRT缺乏症特有的突变外，我们还在内含子2中发现了核苷酸替换。根据关于这种限制性片段长度多态的数据，我们提供了机密证据，表明在日本人APRT缺乏症的不同家系中，致病基因来自于日本人祖先创造的单一祖先基因。除了本项目的初衷外，我们还取得了一些有价值的成果。首先，我们已经诊断出世界上一半以上的APRT缺乏症患者。其次，我们发现日本高达80%的aprt缺乏症家庭被归类为日本型。因此，APRT缺乏症在日本人中特别普遍，至少部分原因是这种突变基因(aprt*J)在日本人(但不是高加索人)中广泛分布。第三，我们发现大多数APRT缺乏症患者没有得到正确的诊断，我们关于这种疾病的报道将对许多这种疾病的患者有益。我们确认，在一个种族群体中，多达80%的单一疾病患者的共同祖先致病基因的证据将影响进化论，并将违背优生学的概念，该概念甚至影响了许多现代国家的法律。较少