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Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders
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. Fo...
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Formato: | Texto |
Lenguaje: | English |
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Bentham Science Publishers Ltd.
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679649/ https://www.ncbi.nlm.nih.gov/pubmed/19440510 http://dx.doi.org/10.2174/138920208784340795 |
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author | O’Driscoll, Mark |
author_facet | O’Driscoll, Mark |
author_sort | O’Driscoll, Mark |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2679649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Bentham Science Publishers Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-26796492009-05-13 Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders O’Driscoll, Mark Curr Genomics Article 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. Bentham Science Publishers Ltd. 2008-05 /pmc/articles/PMC2679649/ /pubmed/19440510 http://dx.doi.org/10.2174/138920208784340795 Text en ©2008 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article O’Driscoll, Mark Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title | Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title_full | Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title_fullStr | Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title_full_unstemmed | Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title_short | Haploinsufficiency of DNA Damage Response Genes and their Potential Influence in Human Genomic Disorders |
title_sort | haploinsufficiency of dna damage response genes and their potential influence in human genomic disorders |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679649/ https://www.ncbi.nlm.nih.gov/pubmed/19440510 http://dx.doi.org/10.2174/138920208784340795 |
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