RT Journal
A1 Ye, Adam Yongxin
A1 Dou, Yanmei
A1 Yang, Xiaoxu
A1 Wang, Sheng
A1 Huang, August Yue
A1 Wei, Liping
T1 A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations
JF Genome Research 
JO Genome Research 
YR 2018 
FD July 01 
VO 28 
IS 7 
SP 943 
OP 951 
DO 10.1101/gr.230003.117 
UL http://genome.cshlp.org/content/28/7/943.abstract 
AB 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 ∼5%, and parental pSNMs occurring during the first three cell divisions contributed 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.