Debacker Kim, Kooy R Frank
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R150-8. doi: 10.1093/hmg/ddm136. Epub 2007 Jun 13.
A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated over the last years. In contrast, a relationship between the second main group of fragile sites characterized by repeat expansion, the rare fragile sites, and mental retardation has been proposed many years ago, but after the molecular cloning of FRAXA and FRAXE both unequivocally involved in mental retardation, no additional fragile sites linked with mental retardation have been cloned for over a decade. The recent cloning of new fragile sites and the identification of the associated genes allow us to readdress this old paradigm and to speculate on the role these might play in human disease.
多年前就有人提出，脆性位点（在培养的染色体上表现为间隙或断裂的特定基因组区域）与人类疾病之间存在关联。过去几年里，已积累了证据表明，以特殊基因组结构为特征、普遍表达的常见脆性位点在癌症中发挥作用。相比之下，多年前就有人提出，以重复扩增为特征的第二类主要脆性位点（罕见脆性位点）与智力迟钝之间存在关联，但在明确与智力迟钝相关的FRAXA和FRAXE分子克隆之后，十多年来没有再克隆出与智力迟钝相关的其他脆性位点。最近新脆性位点的克隆以及相关基因的鉴定，使我们能够重新审视这一旧有模式，并推测它们可能在人类疾病中所起的作用。
