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

• Published in: Genome Research Vol. 16; no. 5; pp. 567 - 575
• Main Authors: Ohno, Mizuki, Miura, Tomofumi, Furuichi, Masato, Tominaga, Yohei, Tsuchimoto, Daisuke, Sakumi, Kunihiko, Nakabeppu, Yusaku
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.05.2006
• Subjects: Adult; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 11 - genetics; DNA Damage; Female; Genome, Human; Guanine - analogs & derivatives; Guanine - analysis; Humans; In Situ Hybridization, Fluorescence; Male; Polymorphism, Single Nucleotide; Recombination, Genetic
• ISSN: 1088-9051; 1549-5469; 1549-5477
• DOI: 10.1101/gr.4769606

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 10(6) 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.