Molecular quantitative trait loci
Molecular quantitative trait loci
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DOI：
10.1038/s43586-022-00188-6
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发表时间：
2023-01-25
期刊：
影响因子：
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通讯作者：
Lappalainen, Tuuli
中科院分区：
文献类型：
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作者：
Aguet, Francois;Alasoo, Kaur;Lappalainen, Tuuli
了解遗传变异的功能影响是人类遗传学的关键挑战之一，因为许多与疾病相关的变异位于非编码区域，具有通常未知的假定基因调控效应。该领域最重要的方法之一是分子数量性状基因座（molQTL）作图，其中遗传变异与可大规模测量的分子性状相关，例如基因表达、剪接和染色质可及性。该领域的成熟和大规模研究已经产生了一套丰富的 molQTL 分析方法，新技术开辟了新的发现领域。在本入门书中，我们讨论了 molQTL 作图的研究设计、输入数据和统计方法，并概述了所得数据的属性以及流行的下游应用。我们回顾了 molQTL 作图的局限性和注意事项，以及未来解决这些问题的潜在方法。随着技术的发展，现在为遗传变异的功能表征提供了许多补充方法，我们预计 molQTL 将仍然是该工具包的重要组成部分，作为唯一可以测量人类天然基因组、细胞和组织背景下的变异的现有方法。
Understanding functional effects of genetic variants is one of the key challenges in human genetics, as much of disease-associated variation is located in non-coding regions with typically unknown putative gene regulatory effects. One of the most important approaches in this field has been molecular quantitative trait locus (molQTL) mapping, where genetic variation is associated with molecular traits that can be measured at scale, such as gene expression, splicing and chromatin accessibility. The maturity of the field and large-scale studies have produced a rich set of established methods for molQTL analysis, with novel technologies opening up new areas of discovery. In this Primer, we discuss the study design, input data and statistical methods for molQTL mapping and outline the properties of the resulting data as well as popular downstream applications. We review both the limitations and caveats of molQTL mapping as well as future potential approaches to tackle them. With technological development now providing many complementary methods for functional characterization of genetic variants, we anticipate that molQTLs will remain an important part of this toolkit as the only existing approach that can measure human variation in its native genomic, cellular and tissue context.