Low-frequency somatic copy number alterations in normal human lymphocytes revealed by large-scale single-cell whole-genome profiling
- Lu Liu1,10,
- He Chen1,10,
- Cheng Sun2,10,
- Jianyun Zhang3,10,
- Juncheng Wang2,
- Meijie Du4,
- Jie Li4,
- Lin Di1,
- Jie Shen5,
- Shuang Geng1,
- Yuhong Pang1,
- Yingying Luo6,
- Chen Wu6,
- Yusi Fu1,
- Zhe Zheng2,
- Jianbin Wang4 and
- Yanyi Huang1,7,8,9
- 1Biomedical Pioneering Innovation Center (BIOPIC) and Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing 100871, China;
- 2National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 102300, China;
- 3Department of Oral Pathology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, and Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China;
- 4School of Life Sciences and Beijing Advanced Innovation Center for Structural Biology (ICSB), Tsinghua University, Beijing 100084, China;
- 5Department of Neurobiology, Capital Medical University, Beijing 100069, China;
- 6Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China;
- 7College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing 100871, China;
- 8Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
- 9Institute for Cell Analysis, Shenzhen Bay Laboratory, Shenzhen 518132, China
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↵10 These authors contributed equally to this work.
Abstract
Genomic-scale somatic copy number alterations in healthy humans are difficult to investigate because of low occurrence rates and the structural variations’ stochastic natures. Using a Tn5-transposase-assisted single-cell whole-genome sequencing method, we sequenced over 20,000 single lymphocytes from 16 individuals. Then, with the scale increased to a few thousand single cells per individual, we found that about 7.5% of the cells had large-size copy number alterations. Trisomy 21 was the most prevalent aneuploid event among all autosomal copy number alterations, whereas monosomy X occurred most frequently in over-30-yr-old females. In the monosomy X single cells from individuals with phased genomes and identified X-inactivation ratios in bulk, the inactive X Chromosomes were lost more often than the active ones.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.275453.121.
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Freely available online through the Genome Research Open Access option.
- Received February 26, 2021.
- Accepted November 15, 2021.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
