A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome.
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.
Ohno
Mizuki
M
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Miura
Tomofumi
T
Furuichi
Masato
M
Tominaga
Yohei
Y
Tsuchimoto
Daisuke
D
Sakumi
Kunihiko
K
Nakabeppu
Yusaku
Y
D000328:Adult; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004249:DNA Damage; D005260:Female; D015894:Genome, Human; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic
C024829:8-hydroxyguanine; D006147:Guanine