Jones Bryony L, Swallow Dallas M
Research Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT UK.
Hugo J. 2011 Dec;5(1-4):13-23. doi: 10.1007/s11568-011-9155-4. Epub 2011 Jul 20.
Cis-acting polymorphisms that affect gene expression are now known to be frequent, although the extent and mechanisms by which such variation affects the human phenotype are, as yet, only poorly understood. Key signatures of cis-acting variation are differences in gene expression that are tightly associated with regulatory SNPs or expression Quantitative Trait Loci (eQTL) and an imbalance of allelic expression (AEI) in heterozygous samples. Such cis-acting sequence differences appear often to have been under selection within and between populations and are also thought to be important in speciation. Here we describe the example of lactase persistence. In medical research, variants that affect regulation in cis have been implicated in both monogenic and polygenic disorders, and in the metabolism of drugs. In this review we suggest that by further understanding common regulatory variations and how they interact with other genetic and environmental variables it will be possible to gain insight into important mechanisms behind complex disease, with the potential to lead to new methods of diagnosis and treatments.
现在已知影响基因表达的顺式作用多态性很常见，尽管这种变异影响人类表型的程度和机制目前仍知之甚少。顺式作用变异的关键特征是与调控单核苷酸多态性（SNP）或表达数量性状基因座（eQTL）紧密相关的基因表达差异，以及杂合样本中等位基因表达（AEI）的不平衡。这种顺式作用序列差异似乎常常在群体内部和群体之间受到选择，并且也被认为在物种形成中很重要。在这里，我们描述乳糖酶持续性的例子。在医学研究中，影响顺式调控的变异已被证明与单基因和多基因疾病以及药物代谢有关。在这篇综述中，我们认为，通过进一步了解常见的调控变异以及它们如何与其他遗传和环境变量相互作用，将有可能深入了解复杂疾病背后的重要机制，从而有可能带来新的诊断和治疗方法。
