Profiling the Genome-Wide Landscape of Short Tandem Repeats by Long-Read Sequencing.

Background: Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases and the regulation of gene expression. Long-read sequencing (LRS) offers a potential solution to genome-wide STR analysis. However, characterizing STRs in human genomes using LRS on a large population scale has not been reported. Methods: We conducted the large LRS-based STR analysis in 193 unrelated samples of the Chinese population and performed genome-wide profiling of STR variation in the human genome. The repeat dynamic index (RDI) was introduced to evaluate the variability of STR. We sourced the expression data from the Genotype-Tissue Expression to explore the tissue specificity of highly variable STRs related genes across tissues. Enrichment analyses were also conducted to identify potential functional roles of the high variable STRs. Results: This study reports the large-scale analysis of human STR variation by LRS and offers a reference STR database based on the LRS dataset. We found that the disease-associated STRs (dSTRs) and STRs associated with the expression of nearby genes (eSTRs) were highly variable in the general population. Moreover, tissue-specific expression analysis showed that those highly variable STRs related genes presented the highest expression level in brain tissues, and enrichment pathways analysis found those STRs are involved in synaptic function-related pathways. Conclusion: Our study profiled the genome-wide landscape of STR using LRS and highlighted the highly variable STRs in the human genome, which provide a valuable resource for studying the role of STRs in human disease and complex traits. Copyright © 2022 Liu, Zhao, Xiao, Zeng, Yuan, Zhou, Fang, He, Li, Zhao, Pan, Wang, Yu, Peng, Wang, Meng, Xu, Sun, Yan, Shen, Jiang, Xia, Wang, Guo, Liang, Li and Tang.

Citation

Zhenhua Liu, Guihu Zhao, Yuhui Xiao, Sheng Zeng, Yanchun Yuan, Xun Zhou, Zhenghuan Fang, Runcheng He, Bin Li, Yuwen Zhao, Hongxu Pan, Yige Wang, Guoliang Yu, I-Feng Peng, Depeng Wang, Qingtuan Meng, Qian Xu, Qiying Sun, Xinxiang Yan, Lu Shen, Hong Jiang, Kun Xia, Junling Wang, Jifeng Guo, Fan Liang, Jinchen Li, Beisha Tang. Profiling the Genome-Wide Landscape of Short Tandem Repeats by Long-Read Sequencing. Frontiers in genetics. 2022;13:810595

PMID: 35601492

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