Novel nucleotide substitutions within the coding region of DNMT2 are in strong linkage disequilibrium in Caucasians and Japanese
Novel nucleotide substitutions within the coding region of DNMT2 are in strong linkage disequilibrium in Caucasians and Japanese
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DOI：
10.1159/000053378
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发表时间：
2001-01-01
期刊：
影响因子：
1.8
通讯作者：
Kay, PH
中科院分区：
文献类型：
--
作者：
Franchina, M;Kay, PH
对胞嘧啶甲基化可能受遗传控制的机制的研究已经导致DNMT2编码区内的单核苷酸多态性的鉴定，这些多态性在不同种族群体中是保守的。DNMT2 I等位基因包括外显子2核苷酸位置104处的G和外显子4核苷酸位置50处的C。替代等位基因DNMT2 II在这些位置分别包含A和T。G在没有C的情况下从未被发现，反之亦然，A在没有T的情况下从未被发现，反之亦然。DNMT2 I和DNMT2 II的基因产物的不同之处在于在密码子101指定的位置包含组氨酸或酪氨酸残基。这种氨基酸取代改变了一个保守的甲基化酶基序的氨基酸组成，该基序被证明与M.HhaI中的s -腺苷甲硫氨酸结合有关，M.HhaI是一种在大小和结构上几乎与DNMT2相同的细菌甲基转移酶。与每个DNMT2等位基因相关的核苷酸取代之间的强连锁不平衡的证明为研究进化和物种形成的分子遗传机制提供了有价值的工具。版权所有(C) 2001 S. Karger AG，巴塞尔
Investigations into mechanims by which cytosine methylation may be genetically controlled have led to the identification of single nucleotide polymorphisms within the coding region of DNMT2 that are conserved in different ethnic groups. The DNMT2 I allele includes a G at nucleotide position 104 of exon 2 and a C at position 50 of exon 4. The alternative allele, DNMT2 II, includes an A and T, respectively, at these positions. G was never found in the absence of C and vice versa and A was never found in the absence of T and vice versa. The gene products of DNMT2 I and DNMT2 II differ by the inclusion of a histidine or tyrosine residue at the position specified by codon 101. This amino acid substitution alters the amino acid composition of a conserved methylating enzyme motif shown to be involved in S-adenosylmethionine binding in M.HhaI, a bacterial methyltransferase that is almost identical to DNMT2 in size and structure. Demonstration of strong linkage disequilibrium between the nucleotide substitutions associated with each DNMT2 allele provides valuable tools for the investigation of molecular genetic mechanisms of evolution and speciation. Copyright (C) 2001 S. Karger AG, Basel.