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Journal of Biomedicine and Biotechnology
Volume 2006, Article ID 56182, 9 pages
Review Article

LINE-1 Endonuclease-Dependent Retrotranspositional Events Causing Human Genetic Disease: Mutation Detection Bias and Multiple Mechanisms of Target Gene Disruption

1INSERM U613, Génétique Moléculaire et Génétique Épidémiologique, Brest 29220, France
2Faculté de Médecine de Brest et des Sciences de la Santé, Université de Bretagne Occidentale, Brest 29238, France
3Etablissement Français du Sang-Bretagne, Rennes 35000, France
4Hôpital Morvan, CHRU Brest, Laboratoire de Génétique Moléculaire et d'Histocompatibilité, Brest 29200, France
5Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park Campus, Cardiff CF14 4XN, United Kingdom

Received 20 April 2005; Revised 11 October 2005; Accepted 13 October 2005

Copyright © 2006 Jian-Min Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


LINE-1 (L1) elements are the most abundant autonomous non-LTR retrotransposons in the human genome. Having recently performed a meta-analysis of L1 endonuclease-mediated retrotranspositional events causing human genetic disease, we have extended this study by focusing on two key issues, namely, mutation detection bias and the multiplicity of mechanisms of target gene disruption. Our analysis suggests that whereas an ascertainment bias may have generally militated against the detection of autosomal L1-mediated insertions, autosomal L1 direct insertions could have been disproportionately overlooked owing to their unusually large size. Our analysis has also indicated that the mechanisms underlying the functional disruption of target genes by L1-mediated retrotranspositional events are likely to be dependent on several different factors such as the type of insertion (L1 direct, L1 trans-driven Alu, or SVA), the precise locations of the inserted sequences within the target gene regions, the length of the inserted sequences, and possibly also their orientation.