Okano Y, Wang T, Eisensmith R C, Güttler F, Woo S L
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Am J Hum Genet. 1990 May;46(5):919-24.
We report the identification of a missense mutation of Glu280 to Lys280 in the phenylalanine hydroxylase (PAH) gene of a phenylketonuria (PKU) patient in Denmark. The mutation is associated with haplotype 1 of the PAH gene in this population. This mutation has previously been found in North Africa, where it is in linkage disequilibrium with haplotype 38. While it is conceivable that this mutation could have been transferred from one haplotype background to another by a double crossover or gene conversion event, the fact that the mutation is exclusively associated with the two different haplotypes in the two distinct populations supports the hypothesis that these two PKU alleles are the result of recurrent mutations in the human PAH gene. Furthermore, since the site of mutation involves a CpG dinucleotide, they may represent hot spots for mutation in the human PAH locus.
我们报告了在丹麦一名苯丙酮尿症（PKU）患者的苯丙氨酸羟化酶（PAH）基因中鉴定出一个谷氨酸280突变为赖氨酸280的错义突变。该突变与该人群中PAH基因的单倍型1相关。此前在北非发现过此突变，在那里它与单倍型38处于连锁不平衡状态。虽然可以想象这种突变可能通过双交换或基因转换事件从一个单倍型背景转移到另一个单倍型背景，但该突变仅与两个不同人群中的两种不同单倍型相关这一事实支持了以下假设：这两个PKU等位基因是人类PAH基因反复突变的结果。此外，由于突变位点涉及一个CpG二核苷酸，它们可能代表人类PAH基因座中的突变热点。
