Maria Maleeha, Pouyanfar Negar, Örd Tiit, Kaikkonen Minna U
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Genes (Basel). 2022 Mar 12;13(3):502. doi: 10.3390/genes13030502.
Genome-wide association studies have successfully mapped thousands of loci associated with complex traits. During the last decade, functional genomics approaches combining genotype information with bulk RNA-sequencing data have identified genes regulated by GWAS loci through expression quantitative trait locus (eQTL) analysis. Single-cell RNA-Sequencing (scRNA-Seq) technologies have created new exciting opportunities for spatiotemporal assessment of changes in gene expression at the single-cell level in complex and inherited conditions. A growing number of studies have demonstrated the power of scRNA-Seq in eQTL mapping across different cell types, developmental stages and stimuli that could be obscured when using bulk RNA-Seq methods. In this review, we outline the methodological principles, advantages, limitations and the future experimental and analytical considerations of single-cell eQTL studies. We look forward to the explosion of single-cell eQTL studies applied to large-scale population genetics to take us one step closer to understanding the molecular mechanisms of disease.
全基因组关联研究已成功定位了数千个与复杂性状相关的基因座。在过去十年中，将基因型信息与大量RNA测序数据相结合的功能基因组学方法，通过表达定量性状基因座（eQTL）分析，鉴定了受GWAS基因座调控的基因。单细胞RNA测序（scRNA-Seq）技术为在复杂和遗传条件下，在单细胞水平上对基因表达变化进行时空评估创造了新的令人兴奋的机会。越来越多的研究已经证明了scRNA-Seq在跨不同细胞类型、发育阶段和刺激的eQTL定位中的作用，而使用大量RNA-Seq方法时这些作用可能会被掩盖。在这篇综述中，我们概述了单细胞eQTL研究的方法学原理、优势、局限性以及未来的实验和分析考虑因素。我们期待着将单细胞eQTL研究应用于大规模群体遗传学的爆发，使我们更接近了解疾病的分子机制。
