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

By Raymond Dalgleish, Paul Flicek, Fiona Cunningham, Alex Astashyn, Raymond E. Tully, Glenn Proctor, Yuan Chen, William M. McLaren, Pontus Larsson, Brendan W. Vaughan, Christophe Beroud, Glen Dobson, Heikki Lehvaslaiho, Peter E.M. Taschner, Johan T. den Dunnen, Andrew Devereau, Ewan Birney, Anthony J. Brookes and Donna R. Maglott


This is the final publisher edited version of the paper published as Genome Medicine, 2010, 2 (24). This version was first published at http://genomemedicine.com/content/2/4/24, Doi: 10.1186/gm145.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)

Publisher: BioMed Central
Year: 2010
DOI identifier: 10.1186/gm145
OAI identifier: oai:lra.le.ac.uk:2381/8001

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  1. 2European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom. 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600
  2. (2000). Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion. Hum Mutat doi
  3. Browser view of LRGs
  4. (2005). Claustres M: UMD (Universal Mutation Database): doi
  5. (2007). Clinical laboratory reports in molecular pathology. Arch Pathol Lab Med
  6. dbSNP: The NCBI database of genetic variation [http://www.ncbi.nlm.nih. gov/SNP/] doi
  7. (1988). de Wet W: Molecular biology of the human fi brillar collagen genes.
  8. (2009). DR: NCBI reference sequences: current status, policy and new initiatives. Nucleic Acids Res doi
  9. ENSEMBL: The EBI/Sanger Institute genome browser [http://www. ensembl.org/] doi
  10. (2010). Ensembl’s 10th year. Nucleic Acids Res doi
  11. (2005). GW: Identifi cation and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm. Neuroscience doi
  12. HbVar: A Database of Human Hemoglobin Variants and Thalassemias [http://globin.bx.psu.edu/hbvar/]
  13. (2008). Hemoglobin research and the origins of molecular medicine. Blood doi
  14. HGVS sequence variation nomenclature doi
  15. (2005). INK4a/ARF: a multifunctional tumor suppressor locus. Mutat Res doi
  16. (1995). L-C: Cystic fi brosis: genotypic and phenotypic variations. Annu Rev Genet doi
  17. (1985). MG: Alternative RNA processing events in human calcitonin/ calcitonin gene-related peptide gene expression. doi
  18. MitoMap: A human mitochondrial genome database [http://www. mitomap.org/] doi
  19. Mutalyzer: a tool for checking sequence variant nomenclature doi
  20. MUTbase: Maintenance and Analysis of Mutation Databases on the World Wide Web [http://bioinf.uta.fi /MUTbase/] doi
  21. (1984). Myers JC: Osteogenesis imperfecta: cloning of a pro-α2(I) collagen gene with a frameshift mutation. doi
  22. OMIM: Online Mendelian Inheritance in Man [http://www.ncbi.nlm.nih. gov/Omim/] doi
  23. Open Variation Database [http://www.lovd.nl/]
  24. (2003). Paalman MH: Standardizing mutation nomenclature: why bother? Hum Mutat doi
  25. (2008). PEM: Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker. Hum Mutat doi
  26. (2007). PGK defi ciency.
  27. (2007). RB: Standard mutation nomenclature in molecular diagnostics: practical and educational challenges. doi
  28. Reference Genomic [http://www.lrg-sequence.org/] doi
  29. RefSeq: NCBI reference sequences [http://www.ncbi.nlm.nih.gov/refseq/] doi
  30. schema language for XML [http://relaxng.org/]
  31. (2001). Sirotkin K: dbSNP: the NCBI database of genetic variation. Nucleic Acids Res doi
  32. (2005). Taschner PEM: LOVD: easy creation of a locus-specifi c sequence variation database using an “LSDB-in-a-box” approach. Hum Mutat doi
  33. (1993). The designation of mutations.
  34. The LRG specifi cation [http://www.lrg-sequence.org/docs/LRG.pdf ]
  35. The RefSeqGene Project [http://www.ncbi.nlm.nih.gov/projects/RefSeq/RSG/] Dalgleish et al.
  36. (1993). Tsui L-C: A suggested nomenclature for designating mutations. Hum Mutat doi
  37. (1999). Vihinen M: MUTbase: maintenance and analysis of distributed mutation databases. Bioinformatics doi
  38. (2002). Wajcman H: HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum Mutat doi

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