Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease.
The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accura...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Oxford University Press
2010
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| Online Access: | http://psasir.upm.edu.my/id/eprint/24407/ http://psasir.upm.edu.my/id/eprint/24407/1/Measurement%20methods%20and%20accuracy%20in%20copy%20number%20variation.pdf |
| _version_ | 1848845028118495232 |
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| author | Aldhous, Marian C. Abu Bakar @ Jamaludin, Suhaili Prescott, Natalie J. Palla, Raquel Soo, Kimberley Mansfield, John C. Mathew, Christopher G. Satsangi, Jack Armour, A. L. |
| author_facet | Aldhous, Marian C. Abu Bakar @ Jamaludin, Suhaili Prescott, Natalie J. Palla, Raquel Soo, Kimberley Mansfield, John C. Mathew, Christopher G. Satsangi, Jack Armour, A. L. |
| author_sort | Aldhous, Marian C. |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies. |
| first_indexed | 2025-11-15T08:40:18Z |
| format | Article |
| id | upm-24407 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-15T08:40:18Z |
| publishDate | 2010 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-244072015-11-02T06:26:11Z http://psasir.upm.edu.my/id/eprint/24407/ Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. Aldhous, Marian C. Abu Bakar @ Jamaludin, Suhaili Prescott, Natalie J. Palla, Raquel Soo, Kimberley Mansfield, John C. Mathew, Christopher G. Satsangi, Jack Armour, A. L. The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies. Oxford University Press 2010 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/24407/1/Measurement%20methods%20and%20accuracy%20in%20copy%20number%20variation.pdf Aldhous, Marian C. and Abu Bakar @ Jamaludin, Suhaili and Prescott, Natalie J. and Palla, Raquel and Soo, Kimberley and Mansfield, John C. and Mathew, Christopher G. and Satsangi, Jack and Armour, A. L. (2010) Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. Human Molecular Genetics, 19 (24). pp. 4930-4938. ISSN 0964-6906; ESSN: 1460-2083 http://hmg.oxfordjournals.org/ English |
| spellingShingle | Aldhous, Marian C. Abu Bakar @ Jamaludin, Suhaili Prescott, Natalie J. Palla, Raquel Soo, Kimberley Mansfield, John C. Mathew, Christopher G. Satsangi, Jack Armour, A. L. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title | Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title_full | Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title_fullStr | Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title_full_unstemmed | Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title_short | Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. |
| title_sort | measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with crohn's disease. |
| url | http://psasir.upm.edu.my/id/eprint/24407/ http://psasir.upm.edu.my/id/eprint/24407/ http://psasir.upm.edu.my/id/eprint/24407/1/Measurement%20methods%20and%20accuracy%20in%20copy%20number%20variation.pdf |