| Co-Investigator(Kenkyū-buntansha) |
WATANABE Tomihiro Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 助手 (50182936)
KAWAI Kazuo Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 助手 (60152899)
TERAI Chihiro Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 講師 (40188660)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Research Abstract |
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
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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
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