Nucleic Acids Research Advance Access published online on August 31, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl591
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Systematic identification of pseudogenes through whole genome expression evidence profiling
Celera Genomics 45 West Gude Dr, Rockville, MD 20850, USA 1 Applied Biosystems Inc 45 West Gude Dr, Rockville, MD 20850, USA
*To whom correspondence should be addressed. Tel: +1 240 453 3154; Fax: +1 240 453 3587; Email: Peter.Li{at}appliedbiosystems.com
Received October 30, 2005. Revised July 28, 2006. Accepted July 31, 2006.
The identification of pseudogenes is an integral and significant part of the genome annotation because of their abundance and their impact on the experimental analysis of functional genes. Most of the computational annotation systems are not optimized for systematic pseudogene recognition, often annotating pseudogenes as functional genes, and users then propagate these errors to subsequent analyses and interpretations. In order to validate gene annotations and to identify pseudogenes that are potentially mis-annotated, we developed a novel approach based on whole genome profiling of existing transcript and protein sequences. This method has two important features: (i) equally detects both processed and non-processed pseudogenes and (ii) can identify transcribed pseudogenes. Applying this method to the human Ensembl gene predictions, we discovered that 2011 (9% of total) Ensembl genes in the categories of known and novel might be pseudogenes based on expression evidence. Of these, 1200 genes are found to have no existing evidence of transcription, and 811 genes are found with transcription evidence but contain significant translation disruption. Approximately 40% of the 2011 identified pseudogenes presented a multi-exon structure, representing non-processed pseudogenes. We have demonstrated the power of whole genome profiling of expression sequences to improve the accuracy of gene annotations.
Present address: Alison Yao, National Institute of Allergy and Infectious Diseases, NIH 6610 Rockledge Dr, Bethesda, MD 20892, USA
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