Send to

Choose Destination
Genome Med. 2017 May 30;9(1):49. doi: 10.1186/s13073-017-0441-1.

Genome annotation for clinical genomic diagnostics: strengths and weaknesses.

Author information

Congenica Ltd, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1DR, UK.
The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Addenbrooke's Hospital and University of Cambridge, Cambridge, CB2 0QQ, UK.
Department of Pediatrics (Neurology), University of Texas Southwestern, Dallas, TX, USA.
Program in Genetics and Genome Biology and Department of Paediatrics (Neurology), The Hospital for Sick Children and University of Toronto, Toronto, Canada.
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, WC1N 3BG, UK.
Chalfont Centre for Epilepsy, Chesham Lane, Chalfont St Peter, Buckinghamshire, SL9 0RJ, UK.
The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Illumina Inc, Great Chesterford, Essex, CB10 1XL, UK.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center