Human Molecular Genetics Advance Access published online on June 13, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm136
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Fragile sites and Human Disease
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
* Address for correspondence: Dr. R. Frank Kooy, Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium, Tel. +32-3-8202630, Fax. +32-3-8202566, Email. Frank.Kooy{at}ua.ac.be
Received April 6, 2007; Revised May 3, 2007; Accepted May 17, 2007
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 allows us to readdress this old paradigm and to speculate on the role these might play in human disease.