Open Access Highly Accessed Correspondence

Locus Reference Genomic sequences: an improved basis for describing human DNA variants

Raymond Dalgleish1*, Paul Flicek2, Fiona Cunningham2, Alex Astashyn3, Raymond E Tully3, Glenn Proctor2, Yuan Chen2, William M McLaren2, Pontus Larsson2, Brendan W Vaughan2, Christophe Béroud4, Glen Dobson5, Heikki Lehväslaiho6, Peter EM Taschner7, Johan T den Dunnen7, Andrew Devereau5, Ewan Birney2, Anthony J Brookes1 and Donna R Maglott3

Author Affiliations

1 Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK

2 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK

3 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA

4 INSERM, U827, Montpellier, F-34000, France

5 NGRL Manchester, Genetic Medicine, 6th Floor, St Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK

6 Computational Bioscience Research Center, King Abdullah University of Science and Technology, P.O. Box 55455, Jeddah 21534, Saudi Arabia

7 Department of Human Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands

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Genome Medicine 2010, 2:24  doi:10.1186/gm145

Published: 15 April 2010

Abstract

As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specific purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-file record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)-approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants affecting human health. Further information can be found on the LRG web site: http://www.lrg-sequence.org webcite.