Doctoral Program in Areas of Basic and Applied Biology (GABBA), University of Porto, Portugal ; IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal ; Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal.
Curr Genomics. 2012 Dec;13(8):623-32. doi: 10.2174/138920212803759703.
With the aid of novel and powerful molecular biology techniques, recent years have witnessed a dramatic increase in the number of studies reporting the involvement of complex structural variants in several genomic disorders. In fact, with the discovery of Copy Number Variants (CNVs) and other forms of unbalanced structural variation, much attention has been directed to the detection and characterization of such rearrangements, as well as the identification of the mechanisms involved in their formation. However, it has long been appreciated that chromosomes can undergo other forms of structural changes - balanced rearrangements - that do not involve quantitative variation of genetic material. Indeed, a particular subtype of balanced rearrangement - inversions - was recently found to be far more common than had been predicted from traditional cytogenetics. Chromosomal inversions alter the orientation of a specific genomic sequence and, unless involving breaks in coding or regulatory regions (and, disregarding complex trans effects, in their close vicinity), appear to be phenotypically silent. Such a surprising finding, which is difficult to reconcile with the classical interpretation of inversions as a mechanism causing subfertility (and ultimately reproductive isolation), motivated a new series of theoretical and empirical studies dedicated to understand their role in human genome evolution and to explore their possible association to complex genetic disorders. With this review, we attempt to describe the latest methodological improvements to inversions detection at a genome wide level, while exploring some of the possible implications of inversion rearrangements on the evolution of the human genome.
近年来，借助新颖而强大的分子生物学技术，越来越多的研究报告表明复杂结构变体参与了几种基因组疾病，这一数字呈显著增长。事实上，随着拷贝数变异（CNVs）和其他形式的不平衡结构变异的发现，人们越来越关注这些重排的检测和特征描述，以及涉及它们形成的机制的鉴定。然而，人们早就意识到，染色体可能会经历其他形式的结构变化——平衡重排，而不会涉及遗传物质的定量变化。事实上，一种特殊的平衡重排——倒位，最近被发现比传统细胞遗传学所预测的更为常见。染色体倒位改变了特定基因组序列的方向，除非涉及编码或调控区域的断裂（并且，忽略其附近的复杂转录效应），否则似乎表型上是沉默的。这一令人惊讶的发现与倒位作为导致不育（最终导致生殖隔离）的机制的经典解释很难协调一致，这促使人们进行了一系列新的理论和实证研究，旨在理解它们在人类基因组进化中的作用，并探索它们与复杂遗传疾病的可能关联。在这篇综述中，我们试图描述在全基因组水平上检测倒位的最新方法学进展，同时探讨倒位重排对人类基因组进化的可能影响。
