About the LRG collaboration
In recognition of the need to create universally accepted reference standards for variant reporting, GEN2PHEN (http://www.gen2phen.org) sponsored a meeting in 2008 with key stakeholders, including EBI, NCBI, HGVS, LSDB curators and other members of the community. The goal of the meeting was to design a reference system that would address the shortcomings of existing systems, including confusion over versioning, and that would allow consistent and unambiguous reporting of variants in clinically relevant loci. The new system, founded on the RefSeqGene project, was named Locus Reference Genomic (LRG). As of October 2013, over 700 LRGs have been created, of which over 400 are public and in use by the community (http://www.lrg-sequence.org/LRG). The aim of the project is to create an LRG for every locus with clinical implications.
An LRG is a manually curated record that contains stable and thus, un-versioned reference sequences designed specifically for reporting sequence variants with clinical implications. Each LRG contains a stable “fixed” section and a regularly updated “updatable” section. The fixed section contains stable genomic DNA sequence for the region of interest, transcripts and proteins deemed essential for reporting variants, and an LRG-specific exon numbering system. The updatable section contains the most recent biological information for each LRG region, including mapping information, annotation of all transcripts and overlapping genes in the region, and legacy exon and amino acid numbering systems. The sequences of each LRG are chosen in collaboration with research and diagnostic laboratories, LSDB (locus specific database) curators and mutation consortia with expertise in the region of interest. Additional information on collaborators can be found here http://lrg-sequence.org/lrg-collaborators.
The creation of an LRG involves several steps:
- LRG requested - Collaborators (for example, LSDB curators, members of diagnostic and research communities and/or clinical experts from specific disease areas, etc.) can request an LRG following guidelines found here http://www.lrg-sequence.org/lrg-request.
- RefSeqs reviewed and RefSeqGene released by NCBI
- Pending LRG created by NCBI and EBI
- Experts in LRG region of interest contacted for input by EBI. For more on experts see above and http://lrg-sequence.org/lrg-collaborators.
- Transcripts reviewed by LRG curators at EBI. Publicly available data from RefSeqGene and Ensembl is scrutinized for each transcript in the LRG region. Only transcripts with good biological understanding and essential for reporting variants will be included. Changes can be made to a pending record at this stage, if necessary
- Final review performed by LRG curators at EBI
- LRG published and collaborators informed
EBI and NCBI are committed to developing the technical solutions, as well as computational and visual tools to work with LRG sequences. This enables all the information reported on an LRG to be integrated with the human genome reference sequence.
For more information on the specification and LRGs, see the following publications:
- Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants, MacArthur JA et al., Nucleic Acids Res. 2014 Jan (doi: 10.1093/nar/gkt1198)
- Locus Reference Genomic sequences: an improved basis for describing human DNA variants, Dalgleish R et al., Genome Med. 2010, 2:24
- The LRG specification document
- Conventional wisdom (Editorial), Nature Genetics 2010, 42, p. 363
- Frequently Asked Questions (FAQs)
- LRG video presentation: a webinar of ~30min providing an overview and demo of the LRG resource.
For more information on how the RefSeqGene records relate to the LRG project, please refer to this document.
The LRG project imposes no restrictions on access to, or use of, the data provided. The code written by the members of the project is provided under the Apache 2.0 licence.
This website lists existing LRG sequences and has a FTP site for downloading LRGs. If you would like to give us feedback, please email us at firstname.lastname@example.org. To create an LRG for your region of interest, please contact us at email@example.com.