- Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants. [PMID: 24285302]
Jacqueline A L MacArthur, Joannella Morales, Ray E Tully, Alex Astashyn, Laurent Gil, Elspeth A Bruford, Pontus Larsson, Paul Flicek, Raymond Dalgleish, Donna R Maglott, Fiona Cunningham
Nucleic acids research 2014:42(Database issue)
15 Citations (Google Scholar as of 2016-03-01)
Abstract: Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain internationally recognized stable reference sequences designed specifically for reporting clinically relevant sequence variants. Each LRG is contained within a single file consisting of a stable 'fixed' section and a regularly updated 'updatable' section. The fixed section contains stable genomic DNA sequence for a genomic region, essential transcripts and proteins for variant reporting and an exon numbering system. The updatable section contains mapping information, annotation of all transcripts and overlapping genes in the region and legacy exon and amino acid numbering systems. LRGs provide a stable framework that is vital for reporting variants, according to Human Genome Variation Society (HGVS) conventions, in genomic DNA, transcript or protein coordinates. To enable translation of information between LRG and genomic coordinates, LRGs include mapping to the human genome assembly. LRGs are compiled and maintained by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). LRG reference sequences are selected in collaboration with the diagnostic and research communities, locus-specific database curators and mutation consortia. Currently >700 LRGs have been created, of which >400 are publicly available. The aim is to create an LRG for every locus with clinical implications.
- Conventional wisdom. [PMID: 20428090]
Nature genetics 2010:42(5)
71 Citations (Google Scholar as of 2016-04-18)
Abstract: Recent agreement on stable reference sequences for reporting human genetic variants now allows us to mandate the use of the allele naming conventions developed by the Human Genome Variation Society.
- Locus Reference Genomic sequences: an improved basis for describing human DNA variants. [PMID: 20398331]
Raymond Dalgleish, Paul Flicek, Fiona Cunningham, Alex Astashyn, Raymond E Tully, Glenn Proctor, Yuan Chen, William M McLaren, Pontus Larsson, Brendan W Vaughan, Christophe Béroud, Glen Dobson, Heikki Lehväslaiho, Peter Em Taschner, Johan T den Dunnen, Andrew Devereau, Ewan Birney, Anthony J Brookes, Donna R Maglott
Genome medicine 2010:2(4)
69 Citations (Google Scholar as of 2016-04-18)
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.