Postzygotic single-nucleotide mosaicisms in whole-genome sequences of   clinically unremarkable individuals

doi:10.1038/cr.2014.131

CORC > 北京大学 > 生命科学学院

	Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals
	Huang, August Y. ; Xu, Xiaojing ; Ye, Adam Y. ; Wu, Qixi ; Yan, Linlin ; Zhao, Boxun ; Yang, Xiaoxu ; He, Yao ; Wang, Sheng ; Zhang, Zheng ; Gu, Bowen ; Zhao, Han-Qing ; Wang, Meng ; Gao, Hua ; Gao, Ge ; Zhang, Zhichao ; Yang, Xiaoling ; Wu, Xiru ; Zhang, Yuehua ; Wei, Liping
刊名	细胞研究英文版
	2014
关键词	single-nucleotide mutation postzygotic mosaicism Dravet syndrome next-generation sequencing Bayesian model DETECTABLE CLONAL MOSAICISM SOMATIC MUTATIONS DRAVET SYNDROME MATERNAL MICROCHIMERISM SENSITIVE DETECTION HUMAN TISSUES PIK3CA CAUSE HUMAN BRAIN CANCER DISEASE
DOI	10.1038/cr.2014.131
英文摘要	Postzygotic single-nucleotide mutations (pSNMs) have been studied in cancer and a few other overgrowth human disorders at whole-genome scale and found to play critical roles. However, in clinically unremarkable individuals, pSNMs have never been identified at whole-genome scale largely due to technical difficulties and lack of matched control tissue samples, and thus the genome-wide characteristics of pSNMs remain unknown. We developed a new Bayesian-based mosaic genotyper and a series of effective error filters, using which we were able to identify 17 SNM sites from similar to 80x whole-genome sequencing of peripheral blood DNAs from three clinically unremarkable adults. The pSNMs were thoroughly validated using pyrosequencing, Sanger sequencing of individual cloned fragments, and multiplex ligation-dependent probe amplification. The mutant allele fraction ranged from 5%-31%. We found that C. T and C. A were the predominant types of postzygotic mutations, similar to the somatic mutation profile in tumor tissues. Simulation data showed that the overall mutation rate was an order of magnitude lower than that in cancer. We detected varied allele fractions of the pSNMs among multiple samples obtained from the same individuals, including blood, saliva, hair follicle, buccal mucosa, urine, and semen samples, indicating that pSNMs could affect multiple sources of somatic cells as well as germ cells. Two of the adults have children who were diagnosed with Dravet syndrome. We identified two non-synonymous pSNMs in SCN1A, a causal gene for Dravet syndrome, from these two unrelated adults and found that the mutant alleles were transmitted to their children, highlighting the clinical importance of detecting pSNMs in genetic counseling.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000344993600008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Cell Biology; SCI(E); PubMed; 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 6; ARTICLE; zhangyhd@hotmail.com; weilp@mail.cbi.pku.edu.cn; 11; 1311-1327; 24
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/188915]
专题	生命科学学院
推荐引用方式 GB/T 7714	Huang, August Y.,Xu, Xiaojing,Ye, Adam Y.,et al. Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals[J]. 细胞研究英文版,2014.
APA	Huang, August Y..,Xu, Xiaojing.,Ye, Adam Y..,Wu, Qixi.,Yan, Linlin.,...&Wei, Liping.(2014).Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals.细胞研究英文版.
MLA	Huang, August Y.,et al."Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals".细胞研究英文版 (2014).