Frequency of abnormal human haemoglobins caused by C----T transitions in CpG dinucleotides.
Frequency of abnormal human haemoglobins caused by C----T transitions in CpG dinucleotides.
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由 CpG 二核苷酸中的 C----T 转换引起的异常人类血红蛋白的频率。
DOI：
10.1016/0301-4622(90)88004-c
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发表时间：
1990
影响因子：
3.8
通讯作者：
Perutz,MF
中科院分区：
文献类型：
--
作者：
Perutz,MF
很大一部分人类遗传疾病显然是由甲基化CpG二核苷酸中胞嘧啶残基的脱氨基作用引起的。当C以5-甲基胞嘧啶的形式存在时，它们的突变率已知是高的，但当它未甲基化时，被认为是正常的。β-珠蛋白基因含有5个CpG二核苷酸，γ-珠蛋白基因含有2个CpG二核苷酸，每个α-珠蛋白基因含有35个CpG二核苷酸。β和γ-珠蛋白基因中的CpG二核苷酸是甲基化的，而α-珠蛋白基因中的CpG二核苷酸甲基化不足。因此，人们会认为CpG二核苷酸是β和γ-珠蛋白基因突变的常见来源，而不是α-珠蛋白基因突变的常见来源。事实上，证据表明CpG二核苷酸是α和β珠蛋白基因突变的常见来源。这表明，甲基化和未甲基化的CpG二核苷酸的突变率都异常高，这与已发表的证据相矛盾，或者某些个体的α-珠蛋白基因中的某些CpG二核苷酸被甲基化并因此发生突变的可能性有限。
A large part of human genetic disease apparently arises from deamination of cytosine residues in methylated CpG dinucleotides. Their mutation rate is known to be high when C is present as 5-methyl-cytosine, but is believed to be normal when it is unmethylated. Theβ-globin gene contains five, theγ-globin gene two, and each of theα-globin genes contains 35 CpG dinucleotides. The CpG dinucleotides in theβandγ-globin genes are methylated, while those in theα-globin genes are under-methylated. One would therefore have expected the CpG dinucleotides to be a frequent source of mutations in theβandγ-globin genes, but not in theα-globin genes. In fact, the evidence points to CpG dinucleotides being a frequent source of mutations in both theαandβ-globin genes. This suggests either that the mutation rates of both methylated and unmethylated CpG dinucleotides are abnormally high, which conflicts with published evidence, or that there is a finite chance of some of these in theα-globin genes of certain individuals being methylated and therefore subject to mutation.