Kuzmin A I, Eisensmith R C, Goltsov A A, Sergeeva N A, Schwartz E I, Woo S L
Department of Cell Biology, Baylor College of Medicine, Houston, Tex. 77030, USA.
Eur J Hum Genet. 1995;3(4):246-55. doi: 10.1159/000472305.
Phenylketonuria (PKU) is an autosomal recessive disorder associated with a deficiency of hepatic phenylalanine hydroxylase (PAH). Although the molecular lesions present in the PAH genes of PKU patients have previously been determined in several Slavic populations, little is known regarding the molecular basis of PKU in the non-Slavic populations of the former Soviet Union. Guthrie card samples from twenty-one classical PKU patients residing in the Tatarian Republic were examined by a combination of denaturing gradient gel electrophoresis and direct sequence analysis. Twelve patients were of Tatarian ancestry, five were of Russian ancestry, and four were of mixed Tatarian and Russian ancestry. Two of the Tatarian patients were related, sharing one mutant allele. The single major allele identified in this study was R408W/RFLP haplotype 2/VNTR 3, which was present on 11/14 or 78.6% of all mutant chromosomes of Slavic origin, but on only 10/27 or 37.0% of mutant chromosomes of Tatarian origin. This result suggests that this allele was introduced into central Asian populations during the eastward expansion of Slavs across the Eurasian landmass. A significant influence of Turkic peoples on Tatars can be inferred from the presence of R261Q. IVS10nt546g --> a, L48S, IVS2nt5g --> c and P281L, all of which are relatively common among Turks or have been observed in Mediterranean populations. Together, these alleles are present on 11/27 or 40.7% of all mutant chromosomes in ethnic Tatars. Surprisingly, the common Scandinavian mutation IVS12ntlg --> a was also present in Tataria, as was the delta agE221D222fs mutation found previously only in Denmark. Thus, some direct or indirect gene flow from Scandinavian into Tataria seems evident. Finally, the complete absence of PAH mutations previously observed in Oriental populations suggests that there was little gene flow into Tataria from Eastern Asia.
苯丙酮尿症（PKU）是一种常染色体隐性疾病，与肝脏苯丙氨酸羟化酶（PAH）缺乏有关。尽管此前已在几个斯拉夫族群中确定了PKU患者PAH基因中的分子病变，但对于前苏联非斯拉夫族群中PKU的分子基础知之甚少。通过变性梯度凝胶电泳和直接序列分析相结合的方法，对居住在鞑靼斯坦共和国的21例典型PKU患者的Guthrie卡片样本进行了检测。其中12例患者为鞑靼族裔，5例为俄罗斯族裔，4例为鞑靼族与俄罗斯族的混血。2例鞑靼族患者有亲属关系，共享一个突变等位基因。本研究中鉴定出的单一主要等位基因为R408W/RFLP单倍型2/VNTR 3，在所有斯拉夫起源的突变染色体中占11/14或78.6%，但在鞑靼起源的突变染色体中仅占10/27或37.0%。这一结果表明，该等位基因是在斯拉夫人向东扩张穿越欧亚大陆期间引入中亚人群的。从R261Q的存在可以推断出突厥民族对鞑靼人有重大影响。IVS10nt546g→a、L48S、IVS2nt5g→c和P281L，所有这些在突厥人中相对常见或在地中海人群中被观察到。这些等位基因一起出现在所有鞑靼族突变染色体的11/27或40.7%中。令人惊讶的是，常见的斯堪的纳维亚突变IVS12nt1g→a也出现在鞑靼斯坦，之前仅在丹麦发现的δagE221D222fs突变也是如此。因此，从斯堪的纳维亚到鞑靼斯坦似乎有一些直接或间接的基因流动。最后，此前在东方人群中观察到的PAH突变完全不存在，这表明从东亚流入鞑靼斯坦的基因很少。
