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CpG/CpNpG motifs in the coding region are preferred sites for mutagenesis in the breast cancer susceptibility genes
Author(s) -
Cheung Lydia W.T.,
Lee Yiu Fai,
Ng Tuen Wai,
Ching Wai Ki,
Khoo Ui Soon,
Ng Michael K.P.,
Wong Alice S.T.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.08.061
Subject(s) - cpg site , genetics , biology , gene , mutagenesis , coding region , dna methylation , mutation , computational biology , gene expression
The range of BRCA1 / BRCA2 gene mutations is diverse and the mechanism accounting for this heterogeneity is obscure. To gain insight into the endogenous mutational mechanisms involved, we evaluated the association of specific sequences (i.e. CpG/CpNpG motifs, homonucleotides, short repeats) and mutations within the genes. We classified 1337 published mutations in BRCA1 (1765 BRCA2 mutations) for each specific sequence, and employed computer simulation combined with mathematical calculations to estimate the true underlying tendency of mutation occurrence. Interestingly, we found no mutational bias to homonucleotides and repeats in deletions/insertions and substitutions but striking bias to CpG/CpNpG in substitutions in both genes. This suggests that methylation‐dependent DNA alterations would be a major mechanism for mutagenesis.