Khajoee Vahid, Ihara Kenji, Kira Ryutaro, Takemoto Megumi, Torisu Hiroyuki, Sakai Yasunari, Guanjun Jia, Hee Park Myoung, Tokunaga Katsushi, Hara Toshiro
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hum Genet. 2003 Mar;112(3):244-8. doi: 10.1007/s00439-002-0870-8. Epub 2003 Jan 9.
A nonsense mutation at codon 95 (R95X) in the C9 gene is responsible for most Japanese C9 deficiency (C9D) cases, with a carrier frequency of 6.7%. Upon analysis of microsatellite markers and newly identified dinucleotide repeat number polymorphisms in the 3' flanking region of the C9 gene, a founder effect was demonstrated for the R95X mutation of the C9 gene in Japanese. Screening for the R95X mutation in Korean and Chinese individuals showed that the R95X carrier frequencies in Koreans and Chinese were 2.0% and 1.0%, respectively. Although homozygotes for the R95X mutation were not found in Korea or China, the shared haplotype of the dinucleotide repeat number polymorphisms appeared to be associated with the R95X mutation in the heterozygotes in Korea and China. The founder effect found in East Asians (Japanese, Koreans and Chinese) but not in Caucasians, as well as the haplotype sharing in only a small chromosomal interval, suggested that the R95X mutation of C9 gene was ancient and had occurred after the divergence of East Asians and Caucasians, and before migration of the Yayoi people to Japan. Since the mortality of meningococcal infections in complement-deficient patients is lower than that in normal individuals, a founder effect and a selective advantage in isolation might be the main reasons for the high frequency of the R95X mutation in Japan.
C9基因第95位密码子（R95X）处的无义突变是导致大多数日本C9缺陷（C9D）病例的原因，其携带频率为6.7%。通过对C9基因3'侧翼区域的微卫星标记和新发现的二核苷酸重复数多态性进行分析，证实了日本人群中C9基因R95X突变存在奠基者效应。对韩国人和中国人进行R95X突变筛查发现，韩国人和中国人的R95X携带频率分别为2.0%和1.0%。虽然在韩国或中国未发现R95X突变的纯合子，但二核苷酸重复数多态性的共享单倍型似乎与韩国和中国杂合子中的R95X突变相关。在东亚人（日本人、韩国人和中国人）中发现了奠基者效应，而在高加索人中未发现，并且仅在一个小的染色体区间内存在单倍型共享，这表明C9基因的R95X突变是古老的，发生在东亚人和高加索人分化之后，以及弥生人迁移到日本之前。由于补体缺陷患者中脑膜炎球菌感染的死亡率低于正常个体，奠基者效应和隔离中的选择优势可能是日本R95X突变高频率的主要原因。
