| 1. |
Mizuki Ohno, Spontaneous de novo germline mutations in humans and mice
rates, spectra, causes and consequences, Genes and Genetic Systems, 10.1266/ggs.18-00015, 94, 1, 13-22, 2019.01, Germline mutations are the origin of genetic variation and are widely considered to be the driving force of genome evolution. The rates and spectra of de novo mutations (DNMs) directly affect evolutionary speed and direction and thereby establish species-specific genomic futures in the long term. This has resulted in a keen interest in understanding the origin of germline mutations in mammals. Accumulating evidence from next-generation sequencing and family-based analysis indicates that the frequency of human DNMs varies according to sex, age and local genomic context. Thus, it is likely that there are multiple causes and drivers of mutagenesis, including spontaneous DNA lesions, DNA repair status and DNA polymerase errors. In this review, recent studies of human and mouse germline DNMs are discussed, and the rates and spectra of spontaneous germline DNMs in the mouse mutator lines Pold1exo/exo and TOY-KO (Mth1−/−/Ogg1−/−/ Mutyh−/− triple knockout) are summarized in the context of endogenous causes and mechanisms.. |
| 2. |
Arikuni Uchimura, Mayumi Higuchi, Yohei Minakuchi, Ohno Mizuki, Atsushi Toyoda, Asao Fujiyama, Ikuo Miura, Shigeharu Wakana, Jo Nishino, Takeshi Yagi, Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice, Genome Research, 10.1101/gr.186148.114, 25, 8, 1125-1134, 2015.08, The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates. We estimated the base-substitution mutation rate to be 5.4 × 10-9 (95% confidence interval = 4.6 × 10-9-6.5 × 10-9) per nucleotide per generation in C57BL/6 laboratory mice, about half the rate reported in humans. The mutation rate in mutator mice was 17 times that in wild-type mice. Abnormal phenotypes were 4.1-fold more frequent in the mutator lines than in the wild-type lines. After several generations, the mutator mice reproduced at substantially lower rates than the controls, exhibiting low pregnancy rates, lower survival rates, and smaller litter sizes, and many of the breeding lines died out. These results provide fundamental information about mouse genetics and reveal the impact of germline mutation rates on phenotypes in a mammalian population.. |
| 3. |
Ohno Mizuki, SAKUMI Kunihiko, Fukumura Ryutaro, Masato Furuichi, Iwasaki Yuki, Hokama Masaaki, Ikemura Toshimichi, Teruhisa Tsuzuki, Gondo Yoichi, Yusaku Nakabeppu, 8-oxoguanine causes spontaneous de novo germline mutations in mice , Scientific reports, 10.1038/srep04689, 4:4689, 2014.04. |
| 4. |
Ichikawa J, Tsuchimoto D, Oka S, Ohno M, Furuichi M, Sakumi K, Nakabeppu Y., Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death., DNA Repair, 7(3):418-430, 2008.03. |
| 5. |
Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y., Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs., EMBO Journal.,27(2):421-432., 2008.01. |
| 6. |
Ohno M, Miura T, Furuichi M, Tominaga Y, Tsuchimoto D, Sakumi K, Nakabeppu Y., A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome., Genome Res.,6(5):567-575, 2006.05. |
| 7. |
Yamaguchi, H., Kajitani K., Dan Y., Furuichi M., Ohno M., Sakumi K., Kang D. and Nakabeppu Y., MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine., Cell Death Differ,13(4):551-563, 2006.04. |
| 8. |
Yoshimura, D., K. Sakumi, M. Ohno, Y. Sakai, M. Furuichi, S. Iwai, and Y. Nakabeppu.,, An oxidized purine nucleoside triphosphatase, MTH1 suppresses cell death caused by oxidative stress., J. Biol. Chem.,278:37965-37973, 2003.09. |
| 9. |
Ohno M, Fukagawa T, Lee JS, Ikemura T., Triplex-forming DNAs in the human interphase nucleus visualized in situ by polypurine/polypyrimidine DNA probes and antitriplex antibodies., Chromosoma. 2002 Sep;111(3):201-13. Epub 2002 Jul 16., 2002.09. |
| 10. |
Mizuki Ohno, Tenzen T., Watanabe Y., Yamagata T., Kanaya S., Ikemura T., Non-B DNA structures spatially and sequence-specifically associated with individual cetromeres in the human interphase nucleus, Chromosome Today. Vol.13, 2000.10. |
| 11. |
Ohno M, Aoki N, Sasaki H., Allele-specific detection of nascent transcripts by fluorescence in situ hybridization reveals temporal and culture-induced changes in Igf2 imprinting during pre-implantation mouse development., Genes Cells. 2001 Mar;6(3):249-59., 10.1046/j.1365-2443.2001.00417.x, 6, 3, 249-259, 2001.03. |
