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Your search keyword '"Xianing Zheng"' showing total 2 results
Start Over Author "Xianing Zheng" Publisher public library of science (plos)
2 results on '"Xianing Zheng"'

1. Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs.

Author

August Yue Huang, Xiaoxu Yang, Sheng Wang, Xianing Zheng, Qixi Wu, Adam Yongxin Ye, and Liping Wei

Subjects
Genetics, QH426-470
Abstract

Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs). Compared to clonal expansion pSNMs, embryonic pSNMs had higher proportion of C>T mutations with elevated mutation rate at CpG sites. We observed differences in replication timing between these two types of pSNMs, with embryonic and clonal expansion pSNMs enriched in early- and late-replicating regions, respectively. An increased number of embryonic pSNMs were located in open chromatin states and topologically associating domains that transcribed embryonically. Our findings provide new insights into the origin and spatial distribution of postzygotic mosaicism during normal human development.

Published
2018
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2. Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals

Author

Qixi Wu, Adam Yongxin Ye, Jing Guo, Boxun Zhao, Qing-Rong Liu, Yue Huang, Linlin Yan, Xiaoxu Yang, Liping Wei, Xianing Zheng, and Thomas M. Hyde

Subjects
Adult, Cancer Research, Adolescent, Transcription, Genetic, Methyl-CpG-Binding Protein 2, Somatic cell, Rett syndrome, Retrotransposon, Genomics, Biology, Germline, law.invention, MECP2, Exon, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, law, Sequence Homology, Nucleic Acid, Rett Syndrome, Genetics, medicine, Humans, Tissue Distribution, Gene, Molecular Biology, Germ-Line Mutation, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Polymerase chain reaction, 030304 developmental biology, Cerebral Cortex, Neurons, 0303 health sciences, Base Sequence, Mosaicism, Brain, Cortical neurons, medicine.disease, Long Interspersed Nucleotide Elements, Healthy individuals, Case-Control Studies, Mutation, Female, 030217 neurology & neurosurgery, Research Article
Abstract

Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic L1Hs (Human-specific LINE-1) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons—mainly contributed by long genes—than healthy controls, implying that cells carryingMECP2mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MECP2 dysfunction alters their genomic patterns in Rett patients.Author SummaryHuman-specific LINE-1 (L1Hs) is the most active autonomous retrotransposon family in the human genome. Mounting evidence supports that L1Hs retrotransposition occurs postzygotically in the human brain cells, contributing to neuronal genomic diversity, but the extent of L1Hs-driven mosaicism in the brain is debated. In this study, we profiled genome-wide L1Hs insertions among 20 postmortem tissues from Rett patients and matched controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues, with a higher jumping activity in the brain. We further found that MECP2 dysfunction might alter the genomic pattern of somatic L1Hs in Rett patients.

Published
2019
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