Bias in somatic hypermutation of human VH genes.
Bias in somatic hypermutation of human VH genes.
复制标题
人类 VH 基因体细胞超突变的偏差。
DOI：
10.1093/intimm/6.9.1437
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发表时间：
1994
影响因子：
4.4
通讯作者：
Varade,WS
中科院分区：
文献类型：
--
作者：
Insel,RA;Varade,WS
对从人脾脏分离的人VH6Ig基因重排的翻译沉默突变（非抗原选择）进行偏倚分析，以深入了解突变过程的内在特征。代表38个VH6DJ重排的63个克隆总体突变频率为4.5%，替代/沉默（R/S）突变比为2.1,167个独特的沉默突变。沉默突变在以下方面表现出偏向性：(1)靶向CDR1和CDR2，(2)与编码链上的T核苷酸碱基相比，A的突变频率增加，以及(3)转换频率高于转换频率。C→G / C→A、G→C / G→T和A→C / A→T的偏置也存在。观察到突变热点，其中一些与茎环形成的潜在位点相对应。结果表明，人类体细胞突变过程可能针对某些V基因的互补决定区，表现出有利于过渡和特定类型的翻转的特定碱基替换，并且可能只发生在一条DNA链上。
Translationally silent mutations, which are not antigen selected, of human VH6Ig gene rearrangements isolated from human spleen were analyzed for bias to gain insight into intrinsic features of the mutation process. Sixty-three clones representing 38 VH6DJ rearrangements had an overall mutation frequency of 4.5%, a replacement/silent (R/S) mutation ratio of 2.1 and 167 unique silent mutations. The silent mutations showed bias in: (I) targeting to CDR1 and CDR2, (II) an increased frequency of mutations of A compared to T nucleotide bases on the coding strand, and (III) an increased frequency of transitions versus transvereions. Bias of C→G over C→A, of G→C over G→T and of A→C over A→T transvereions was also present. Hot spots of mutation were observed, some which corresponded to potential sites of stem - loop formation. The results suggest that the somatic mutation process in man may be targeted to the complementarity determining region for some V genes, exhibits specific base substitutions favoring transitions and specific types of transversions, and may be occurring on only one DNA strand.