eQTL是个什么鬼

首先,数量性状(Quantitative Trait)是指一个群体内各个体表现为连续变异的性状,相对而言质量性状往往是非黑即白。数量性状一般呈连续的正态分布,难以在个体间分组。控制数量性状的基因位点即QTL(Quantitative Trait Loci)

eQTL(expression Quantitative Trait Loci)即表达数量性状位点,是对数量性状位点的进一步深化,它是指基因组上能调控mRNA和蛋白表达水平的区域。根据eQTL定位到基因组的位置与受调控表达基因位置的远近关系,eQTLs可以分为顺式eQTL(cis-acting)和反式eQTL(trans-acting)。对基因组的遗传变异(如SNPs)和基因的表达谱进行GWAS分析,可以大规模系统的发掘eQTLs。

早期通过多个个体的SNP芯片和cDNA芯片,研究表达与基因突变的关系。随着RNA-seq的大量应用,大规模高通量eQTLs的发掘变得更加容易。eQTL的研究是管理基因组遗传变异与表型变异的中间桥梁,就像表观遗传变异和代谢组是额外的中间层一样。同样的,通过线性混合模型发掘eQTLs要基于基因表达量的正态分布假设,就像数量性状一样。

eQTL

Illustration of the concept of cis and trans expression quantitative trait loci (eQTLs). A) The left-most gene (red) codes for a transcription factor (TF) protein that activates the transcription of genes A (green) and B (blue) by binding to their respective promoters (gray). In the wildtype, or “normal,” scenario all genes are transcribed at their full potential, as indicated by the bar graph on the right. B) A variant (i.e., polymorphism) (triangle) in gene A’s promoter region hinders TF binding, causing a reduction in the rate at which gene A is transcribed, while gene B is unaffected. Thus, gene A is being regulated by a cis eQTL because its level of expression is associated with a nearby polymorphism located on the same chromosome. C) A polymorphism in the TF gene’s DNA binding region (hexagon)—the region of the TF protein that binds to gene promoters—hinders binding with all downstream promoters, regardless of whether the regulated gene is located near the TF gene, like gene A, or located on an entirely different chromosome, like gene B. In fact, all genes regulated by this TF would be linked to a trans eQTL at the site of this TF polymorphism.

图片和图注解释引自:https://pubs.niaaa.nih.gov/publications/arcr343/306-317.htm


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