The origin of the most common mutation of adenine phosphoribosyltransferase among Japanese goes back to a prehistoric era

摘要

The incidence of adenine phosphoribosyltransferase (APRT) deficiency is higher among Japanese nationals than among other ethnic groups, and the most common mutation (APRT*J, ATG to ACG mutation at codon 136) accounts for 68% of the disease-causing genes among Japanese. To investigate the origin of these mutations, we studied the geographical distribution of the mutant genes in Japan. TheAPRT*Jmutation is distributed nearly uniformly in the four main islands of Japan and Okinawa, suggesting a very early origin. The products of PCR amplification between positions 2344 and 2750 of the genomic APRT sequence were examined by SSCP analysis in random blood samples from Japanese, Korean, and Taiwanese nationals. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for theAPRT*Jmutation, giving a calculated heterozygote frequency of 1.1% among Japanese for the entire APRT deficiency. None of 231 Taiwanese samples contained heterozygotes for theAPRT*Jmutation, while 2 (0.53%) of 356 Korean samples were heterozygous. In addition to theAPRT*Jsequence, a total of five variant sequences was found. Sequencing one variant revealed a base substitution in intron 4, suggesting therefore that they are harmless mutations. Since theAPRT*Jmutation is present in Koreans and Okinawans who share ancestors only before the Yayoi era (third centurybcto third centuryad), the origin of theAPRT*Jmutation predates 300bc.