东方人苯丙酮尿症的分子遗传学—苯丙氨酸羟化酶基因中一终止突变与单体型4的连锁不平衡性

应用聚合酶链反应(PCR)方法扩增苯丙氨酸羟化酶(PAH)基因的每个外显子及其侧翼的内含子,并克隆到M 13载体中进行序列分析。发现中国人苯丙酮尿症(Phenylketonuria,PKU)患者的PAH基因外显子3中有1个Arg~(111)→Ter~(111)的点突变,此突变与东方人最常见的突变单体型4呈连锁不平衡。此突变占中国人PAH等位基因的10％左右,但不存在于高加索人群中,表明在种族分化过程中PAH基因位点发生了互不相关的突变事件。

Molecular Genetics of Phenylketonuria in Orientals-Linkage Disequilibrium between a Termination Mutation and Haplotype 4 of the Phenylalanine Hydroxylase Gene

Phenylketonuria (PKU) is a common metabolic disorder among Chinese, with a prevalence of about 1 in 16 500 births. This frequency is very similar to that among Caucasians. Individual exons of the phenylalanine hydroxylase (PAH) gene with flanking introns were amplified by the polymerase chain reaction and cloned into Ml3 for sequence analysis. An Arg111-to-Ter111 mutation was identified in exon 3 of the PAH gene in a Chinese PKU patient. The mutation is in linkage disequilibrium with the mutant haplotype 4, most prevalent among Orientals. The mutation accounts for about 10% of Chinese PKU al-leles and is not found in Caucasians, demonstrating that independent mutational events occured in the PAH locus after racial divergence.