A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome

Mizuki Ohno, Tomofumi Miura, Masato Furuichi, Yohei Tominaga, Daisuke Tsuchimoto, Kunihiko Sakumi, Yusaku Nakabeppu

研究成果: Contribution to journalArticle査読

65 被引用数 (Scopus)

抄録

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state level of 8-oxoG in the nuclear genome of a human cell has been estimated to be several residues per 106 guanines. In the present study, to clarify the genome-wide distribution of 8-oxoG in the steady state, we performed fluorescence in situ detection of 8-oxoG on human metaphase chromosomes using a monoclonal antibody. Multiple dot-like signals were observed on each metaphase chromosome. We then mapped the position of the signal at megabase resolution referring to the cytogenetically identified chromosomal band, and demonstrated that 8-oxoG is unevenly distributed in the normal human genome and that the distribution pattern is conserved among different individuals. Moreover, we found that regions with a high frequency of recombination and single nucleotide polymorphisms (SNPs) are preferentially located within chromosomal regions with a high density of 8-oxoG. Our findings suggest that 8-oxoG is one of the main causes of frequent recombinations and SNPs in the human genome, which largely contribute to the genomic diversity in human beings.

本文言語英語
ページ(範囲)567-575
ページ数9
ジャーナルGenome Research
16
5
DOI
出版ステータス出版済み - 5 2006

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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