Why did my gene change?
As a member of the Ensembl Outreach team, who is actively involved with training and user support, I often have to answer the question, “Why did the annotation of my favourite gene change?”
There are a few driving forces behind the changes in the annotation of any given gene. Two of those are the growing number of sequences that are deposited in sequence databases nightly, and the updates to the genomic assembly of a given species. Regardless of the reason, changes and improvements will result in a revised and refined annotation of our Ensembl geneset.
However, clinical researchers in particular may prefer to work in a more controlled, less changeable environment. You may wonder then: “Is there annotation in Ensembl that won’t change?” Yes, there is!
Are there genes that don’t change?
There is a set of gene sequences where changes are strictly prohibited.
These are the LRG records. An LRG or Locus Reference Genomic has a fixed and stable reference sequence for reporting and diagnosing variants that cause diseases in humans.
More than 700 records have been annotated so far. They have been mapped everywhere in the human genome, with the exception of the Y chromosome and the mtDNA.
The majority of these 700 records (59%) are publicly available on the LRG website, whereas the remaining are still in the validation phase, carried out manually by LRG curators. The ultimate goal is to provide an LRG record for every single protein-coding gene in the human genome. It’s certainly a mammoth task! So, genes with clinical implications will be prioritised.
Stable sequences allow clinical geneticists and the research community to report their variation data in a more controlled and stable framework. They will be able to perform consistent comparisons of variants reported in LRG coordinates against other databases and therefore be better equipped when diagnosing diseases.
Viewing LRGs in Ensembl
In addition to the LRG website, clinical geneticists and others can investigate any of the public LRG records in Ensembl too, where they can be viewed in the context of our comprehensive annotation of genes, variants and regulatory features, among many other features.
Use Ensembl to search for an LRG and get all the variants that map to it. You can then check the functional impact of these variants. For more tips on how to investigate LRG records in Ensembl, contact us.
Can I request my own LRG?
You can request an LRG record for a clinically relevant gene. For more details on how to submit the request, have a look at the LRG request page.