1. A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome
- Author
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Yusaku Nakabeppu, Masato Furuichi, Yohei Tominaga, Tomofumi Miura, Mizuki Ohno, Daisuke Tsuchimoto, and Kunihiko Sakumi
- Subjects
Adult ,Male ,Nuclear gene ,Guanine ,Single-nucleotide polymorphism ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Article ,chemistry.chemical_compound ,Genetics ,Humans ,heterocyclic compounds ,Metaphase ,Genetics (clinical) ,In Situ Hybridization, Fluorescence ,Recombination, Genetic ,Genome, Human ,Chromosomes, Human, Pair 11 ,Chromosome Mapping ,Karyotype ,8-Oxoguanine ,Chromosome Banding ,chemistry ,Human genome ,Female ,Recombination ,DNA Damage - Abstract
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.
- Published
- 2006