Steward, CA;
Parker, APJ;
Minassian, BA;
Sisodiya, SM;
Frankish, A;
Harrow, J;
(2017)
Genome annotation for clinical genomic diagnostics: strengths and weaknesses.
Genome Medicine
, 9
, Article 49. 10.1186/s13073-017-0441-1.
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Abstract
The Human Genome Project and advances in DNA sequencing technologies have revolutionized the identification of genetic disorders through the use of clinical exome sequencing. However, in a considerable number of patients, the genetic basis remains unclear. As clinicians begin to consider whole-genome sequencing, an understanding of the processes and tools involved and the factors to consider in the annotation of the structure and function of genomic elements that might influence variant identification is crucial. Here, we discuss and illustrate the strengths and weaknesses of approaches for the annotation and classification of important elements of protein-coding genes, other genomic elements such as pseudogenes and the non-coding genome, comparative-genomic approaches for inferring gene function, and new technologies for aiding genome annotation, as a practical guide for clinicians when considering pathogenic sequence variation. Complete and accurate annotation of structure and function of genome features has the potential to reduce both false-negative (from missing annotation) and false-positive (from incorrect annotation) errors in causal variant identification in exome and genome sequences. Re-analysis of unsolved cases will be necessary as newer technology improves genome annotation, potentially improving the rate of diagnosis.
| Type: | Article |
|---|---|
| Title: | Genome annotation for clinical genomic diagnostics: strengths and weaknesses |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13073-017-0441-1 |
| Publisher version: | http://dx.doi.org/10.1186/s13073-017-0441-1 |
| Language: | English |
| Additional information: | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated |
| Keywords: | LONG NONCODING RNAS, BURROWS-WHEELER TRANSFORM, HUMAN-CHROMOSOME 22, MESSENGER-RNA, SEQUENCE VARIANTS, CODING SEQUENCE, GENE-EXPRESSION, DNA-SEQUENCE, EPILEPTIC ENCEPHALOPATHIES, PREMESSENGER RNA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1558980 |
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