Journal
GENOME RESEARCH
Volume 28, Issue 7, Pages 943-951Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.230003.117
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Funding
- Ministry of Science and Technology of the People's Republic of China [2015AA020108]
- National Natural Science Foundation of China [31530092]
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The allele fraction (AF) distribution, occurrence rate, and evolutionary contribution of postzygotic single-nucleotide mosaicisms (pSNMs) remain largely unknown. In this study, we developed a mathematical model to describe the accumulation and AF drift of pSNMs during the development of multicellular organisms. By applying the model, we quantitatively analyzed two large-scale data sets of pSNMs identified from human genomes. We found that the postzygotic mutation rate per cell division during early embryogenesis, especially during the first cell division, was higher than the average mutation rate in either male or female gametes. We estimated that the stochastic cell death rate per cell cleavage during human embryogenesis was similar to 5%, and parental pSNMs occurring during the first three cell divisions contributed to similar to 10% of the de novo mutations observed in children. We further demonstrated that the genomic profiles of pSNMs could be used to measure the divergence distance between tissues. Our results highlight the importance of pSNMs in estimating recurrence risk and clarified the quantitative relationship between postzygotic and de novo mutations.
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