Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Santiago de Querétaro 76230, Mexico; Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA; Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA, USA.
Curr Opin Genet Dev. 2021 Feb;66:10-19. doi: 10.1016/j.gde.2020.10.007. Epub 2020 Dec 28.
Allele-specific gene expression can influence disease traits. Non-coding germline genetic variants that alter regulatory elements can cause allele-specific gene expression and contribute to cancer susceptibility. In tumors, both somatic copy number alterations and somatic single nucleotide variants have been shown to lead to allele-specific expression of genes, many of which are considered drivers of tumor growth. Here, we review recent studies revealing the pervasive presence of this phenomenon in cancer susceptibility and progression. Furthermore, we underscore the importance of careful experimental design and computational analysis for accurate allelic expression quantification and avoidance of false positives. Finally, we discuss additional methodological challenges encountered in cancer studies and in the burgeoning field of single-cell transcriptomics.
等位基因特异性基因表达可以影响疾病特征。改变调控元件的非编码种系遗传变异可以导致等位基因特异性基因表达，并导致癌症易感性。在肿瘤中，已经显示体细胞拷贝数改变和体细胞单核苷酸变异导致基因的等位基因特异性表达，其中许多被认为是肿瘤生长的驱动因素。在这里，我们回顾了最近的研究，揭示了这种现象在癌症易感性和进展中的普遍存在。此外，我们强调了仔细的实验设计和计算分析对于准确的等位基因表达定量和避免假阳性的重要性。最后，我们讨论了在癌症研究和新兴的单细胞转录组学领域中遇到的其他方法学挑战。
