Haploinsufficiency of DNA Damage response genes and their potential influence in human genomic disorders

O'Driscoll, M (2008) Haploinsufficiency of DNA Damage response genes and their potential influence in human genomic disorders. Current Genomics, 9 (3). pp. 137-146. ISSN 1389-2029

[img]
Preview
PDF
Download (157kB) | Preview

Abstract

Genomic disorders are a clinically diverse group of conditions caused by gain, loss or re-orientation of a genomic region containing dosage-sensitive genes. One class of genomic disorder is caused by hemizygous deletions resulting in haploinsufficiency of a single or, more usually, several genes. For example, the heterozygous contiguous gene deletion on chromosome 22q11.2 causing DiGeorge syndrome involves at least 20-30 genes. Determining how the copy number variation (CNV) affects human variation and contributes to the aetiology and progression of various genomic disorders represents important questions for the future. Here, I will discuss the functional significance of one form of CNV, haploinsufficiency (i.e. loss of a gene copy), of DNA damage response components and its association with certain genomic disorders. There is increasing evidence that haploinsufficiency for certain genes encoding key players in the cells response to DNA damage, particularly those of the Ataxia Telangiectasia and Rad3-related (ATR)-pathway, has a functional impact. I will review this evidence and present examples of some well known clinically similar genomic disorders that have recently been shown to be defective in the ATR-dependent DNA damage response. Finally, I will discuss the potential implications of a haploinsufficiency-induced defective DNA damage response for the clinical management of certain human genomic disorders.

Item Type: Article
Additional Information: Full text embargoed by publisher until May 2009
Keywords: DNA damage response ATR Haploinsufficiency Genomic disorders
Schools and Departments: School of Life Sciences
Depositing User: Gee Wheatley
Date Deposited: 17 Jul 2008
Last Modified: 17 Aug 2017 09:45
URI: http://sro.sussex.ac.uk/id/eprint/1813
Google Scholar:3 Citations

View download statistics for this item

📧 Request an update