Pastinen Tomi, Hudson Thomas J
McGill University and Genome Quebec Innovation Centre, 740 Drive Penfield Avenue, Montreal, Quebec H3A 1A4, Canada.
Science. 2004 Oct 22;306(5696):647-50. doi: 10.1126/science.1101659.
The systematic screening of the human genome for genetic variants that affect gene regulation should advance our fundamental understanding of phenotypic diversity and lead to the identification of alleles that modify disease risk. There are several challenges in localizing regulatory polymorphisms, including the wide spectrum of cis-acting regulatory mechanisms, the inconsistent effects of regulatory variants in different tissues, and the difficulty in isolating the causal variants that are in linkage disequilibrium with many other variants. We discuss the current state of knowledge and technologies used for mapping and characterizing genetic variation controlling human gene expression.
对人类基因组进行系统筛查以寻找影响基因调控的遗传变异，应能提升我们对表型多样性的基本理解，并有助于识别出可改变疾病风险的等位基因。在定位调控多态性方面存在若干挑战，包括广泛的顺式作用调控机制、调控变异在不同组织中的效应不一致，以及难以分离出与许多其他变异处于连锁不平衡状态的因果变异。我们讨论了用于绘制和表征控制人类基因表达的遗传变异的当前知识状态和技术。
