Low frequency somatic copy number alterations in normal human lymphocytes revealed by large scale single-cell whole genome profiling

Liu, L.; Chen, H.; Sun, C.; Zhang, J.; Wang, J.; Du, M.; Li, J.; Di, L.; Shen, J.; Geng, S.; Pang, Y.; Luo, Y.; Wu, C.; Fu, Y.; Zheng, Z.; Huang, Y.

doi:10.1101/2021.11.10.468149

bioRxiv · 10.1101/2021.11.10.468149

Low frequency somatic copy number alterations in normal human lymphocytes revealed by large scale single-cell whole genome profiling

Liu, L.·Chen, H.·Sun, C.·Zhang, J.·Wang, J.·Du, M.·Li, J.·Di, L.·Shen, J.·Geng, S.·Pang, Y.·Luo, Y.·Wu, C.·Fu, Y.·Zheng, Z.·Huang, Y.

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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, while monosomy X occurred most frequently in over-30-year-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 were the active ones.

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Liu, L., Chen, H., Sun, C., Zhang, J., Wang, J., Du, M., Li, J., Di, L., Shen, J., Geng, S., Pang, Y., Luo, Y., Wu, C., Fu, Y., Zheng, Z., Huang, Y.. 2021-11-13. Low frequency somatic copy number alterations in normal human lymphocytes revealed by large scale single-cell whole genome profiling. https://doi.org/10.1101/2021.11.10.468149

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