The genetic basis of disease has largely focused on coding regions. However, it has become clear that a large proportion of the noncoding genome is functional and harbors genetic variants that contribute to disease etiology. Here, we review recent examples of inherited noncoding alterations that are responsible for Mendelian disorders or act to influence complex traits. We explore both rare and common genetic variants and discuss the wide range of mechanisms by which they affect gene regulation to promote disease. We also debate the challenges and progress associated with identifying and interpreting the functional and clinical significance of genetic variation in the context of the noncoding regulatory landscape.

疾病的遗传基础主要集中在编码区。然而，已经清楚的是，大部分非编码基因组是有功能的，并且具有有助于疾病病因的遗传变异。在这里，我们回顾了导致孟德尔疾病或影响复杂性状的遗传非编码变异的最新例子。我们探索稀有和常见的遗传变异，并讨论它们影响基因调控以促进疾病的广泛机制。我们还将辩论与在非编码监管领域内识别和解释遗传变异的功能和临床意义相关的挑战和进展。