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The consequences of structural genomic alterations in humans: genomic disorders, genomic instability & cancer.

journal contribution
posted on 2023-06-08, 08:28 authored by Rita Colnaghi, Gillian Carpenter, Marcel Volker, Mark O'DriscollMark O'Driscoll
Over the last decade or so, sophisticated technological advances in array-based genomics have firmly established the contribution of structural alterations in the human genome to a variety of complex developmental disorders, and also to diseases such as cancer. In fact, multiple 'novel' disorders have been identified as a direct consequence of these advances. Our understanding of the molecular events leading to the generation of these structural alterations is also expanding. Many of the models proposed to explain these complex rearrangements involve DNA breakage and the coordinated action of DNA replication, repair and recombination machinery. Here, and within the context of Genomic Disorders, we will briefly overview the principal models currently invoked to explain these chromosomal rearrangements, including Non-Allelic Homologous Recombination (NAHR), Fork Stalling Template Switching (FoSTeS), Microhomology Mediated Break-Induced Repair (MMBIR) and Breakage-fusion-bridge cycle (BFB). We will also discuss an unanticipated consequence of certain copy number variations (CNVs) whereby the CNVs potentially compromise fundamental processes controlling genomic stability including DNA replication and the DNA damage response. We will illustrate these using specific examples including Genomic Disorders (DiGeorge/Veleocardiofacial syndrome, HSA21 segmental aneuploidy and rec (3) syndrome) and cell-based model systems. Finally, we will review some of the recent exciting developments surrounding specific CNVs and their contribution to cancer development as well as the latest model for cancer genome rearrangement; '. chromothripsis'. © 2011 Elsevier Ltd.

History

Publication status

  • Published

Journal

Seminars in Cell & Developmental Biology

ISSN

10849521

Publisher

Academic Press Inc

Issue

8

Volume

22

Page range

875-885

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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