title: Locus Reference Genomic sequences: an improved basis for describing human DNA variants.
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.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK. raymond.dalgleish@le.ac.uk.
authors.forename: Raymond
authors.initials: R
authors.lastname: Dalgleish
authors.forename: Paul
authors.initials: P
authors.lastname: Flicek
authors.forename: Fiona
authors.initials: F
authors.lastname: Cunningham
authors.forename: Alex
authors.initials: A
authors.lastname: Astashyn
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Tully
authors.forename: Glenn
authors.initials: G
authors.lastname: Proctor
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: William M
authors.initials: WM
authors.lastname: McLaren
authors.forename: Pontus
authors.initials: P
authors.lastname: Larsson
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Vaughan
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Glen
authors.initials: G
authors.lastname: Dobson
authors.forename: Heikki
authors.initials: H
authors.lastname: Lehväslaiho
authors.forename: Peter Em
authors.initials: PE
authors.lastname: Taschner
authors.forename: Johan T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: Andrew
authors.initials: A
authors.lastname: Devereau
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brookes
authors.forename: Donna R
authors.initials: DR
authors.lastname: Maglott
references.citation: Annu Rev Genet. 1995;29:777-807
references.pmid: 8825494
references.citation: Bioinformatics. 1999 Oct;15(10):852-9
references.pmid: 10705438
references.citation: J Mol Diagn. 2007 Feb;9(1):1-6
references.pmid: 17251329
references.citation: Br J Haematol. 2007 Jan;136(1):3-11
references.pmid: 17222195
references.citation: Hum Mutat. 2000;15(1):7-12
references.pmid: 10612815
references.citation: Mutat Res. 2005 Aug 25;576(1-2):22-38
references.pmid: 15878778
references.citation: Hum Mutat. 2005 Sep;26(3):184-91
references.pmid: 16086365
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D557-62
references.pmid: 19906699
references.citation: Blood. 2008 Nov 15;112(10):3927-38
references.pmid: 18988877
references.citation: Hum Mutat. 2008 Jan;29(1):6-13
references.pmid: 18000842
references.citation: Hum Mutat. 1993;2(4):245-8
references.pmid: 8401532
references.citation: J Biol Chem. 1984 Nov 10;259(21):12941-4
references.pmid: 6092353
references.citation: Proc Natl Acad Sci U S A. 1985 Apr;82(7):1994-8
references.pmid: 3872459
references.citation: Arch Pathol Lab Med. 2007 Jun;131(6):852-63
references.pmid: 17550311
references.citation: Hum Mutat. 2005 Aug;26(2):63-8
references.pmid: 15977173
references.citation: Nucleic Acids Res. 2001 Jan 1;29(1):308-11
references.pmid: 11125122
references.citation: Hum Mutat. 2003 Sep;22(3):181-2
references.pmid: 12938082
references.citation: Ann N Y Acad Sci. 1988;543:109-16
references.pmid: 3063157
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D32-6
references.pmid: 18927115
references.citation: Neuroscience. 2005;133(1):209-20
references.pmid: 15893644
references.citation: Hum Mutat. 2002 Mar;19(3):225-33
references.pmid: 11857738
references.citation: Am J Hum Genet. 1993 Sep;53(3):783-5
references.pmid: 8352285