Gruber Jonathan D
Department of Ecology & Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA.
Methods Mol Biol. 2011;700:153-70. doi: 10.1007/978-1-61737-954-3_11.
Genome-wide association studies are providing exciting new insight into the genetics of complex disease, but oftentimes, the genomic regions associated with the trait of interest are large enough to contain several equally plausible candidate genes. Commonly, no obvious, putatively functional, polymorphisms are found to segregate. In most cases, therefore, functional evaluation of possible regulatory mechanisms is necessary to narrow the list of potential candidates. One approach to functional characterization of such variants is allelic expression (AE) profiling, which provides an assessment of transcriptional differences between two homologous transcripts. In AE, a heterozygous, transcribed single nucleotide polymorphism is used to quantify the relative transcript abundance between two gene copies. A ratio that differs significantly from 1:1 suggests that the sample may be heterozygous for a cis-acting regulatory allele. The pattern of observed cis-regulatory variation in the profiled candidate genes can thus narrow the list of candidates under an association signal substantially. In addition, AE is also an accessible and economical strategy, as it relies heavily upon standard techniques and equipment likely to be present in any disease-mapping laboratory.
全基因组关联研究正在为复杂疾病的遗传学提供令人兴奋的新见解，但通常情况下，与感兴趣的性状相关的基因组区域大到足以包含几个同样合理的候选基因。通常，找不到明显的、假定具有功能的多态性进行分离。因此，在大多数情况下，有必要对可能的调控机制进行功能评估，以缩小潜在候选基因的范围。对这类变异进行功能表征的一种方法是等位基因表达（AE）分析，它可以评估两个同源转录本之间的转录差异。在AE中，杂合的、转录的单核苷酸多态性用于量化两个基因拷贝之间的相对转录本丰度。显著不同于1:1的比例表明样本可能是顺式作用调控等位基因的杂合子。因此，在分析的候选基因中观察到的顺式调控变异模式可以大大缩小关联信号下的候选基因列表。此外，AE也是一种可行且经济的策略，因为它在很大程度上依赖于任何疾病定位实验室可能都有的标准技术和设备。
