Table7_Profiling the Genome-Wide Landscape of Short Tandem Repeats by Long-Read Sequencing.XLSX

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.

研究背景：短串联重复序列（Short tandem repeats, STRs）是一类高度多态的遗传元件，在多种遗传疾病及基因表达调控中发挥关键作用。长读长测序（Long-read sequencing, LRS）为全基因组STR分析提供了潜在解决方案，但目前尚无基于长读长测序在大样本量群体层面开展人类基因组STR特征分析的相关报道。

研究方法：本研究针对193例中国人群无关个体样本，开展了基于长读长测序的大规模STR分析，并完成了人类基因组全基因组STR变异图谱绘制。本研究引入重复动态指数（repeat dynamic index, RDI）以评估STR的多态性程度；从基因型-组织表达（Genotype-Tissue Expression）数据库获取表达数据，以探究高多态性STR相关基因的跨组织表达特异性；同时通过富集分析，明确高多态性STR的潜在功能角色。

研究结果：本研究报道了基于长读长测序的人类STR变异大规模分析结果，并构建了基于长读长测序数据集的参考STR数据库。研究发现，疾病相关STR（disease-associated STRs, dSTRs）及邻近基因表达相关STR（STRs associated with the expression of nearby genes, eSTRs）在普通人群中呈现高度多态性。此外，组织特异性表达分析显示，上述高多态性STR相关基因在脑组织中表达水平最高；富集通路分析表明，此类STR参与突触功能相关通路的调控。

研究结论：本研究基于长读长测序绘制了人类基因组全基因组STR变异图谱，揭示了人类基因组中高度多态的STR位点，为探究STR在人类疾病及复杂性状中的作用提供了宝贵的研究资源。