Earlier this year TGMI hosted an international meeting of seven initiatives that are curating the links between genes and disease. The seven groups are TGMI, ClinGen, OMIM, Orphanet, DDG2P, PanelApp and GHR. Together we have formed the Gene Curation Coalition – the GenCC.
Different aims, different audiences
You might ask if we need multiple groups working on disease gene curation. Our meeting showed we definitely do, at least for now. Curating the links between genes and disease is a very large, very complex task. Each group has been focusing on particular aspects of gene curation. So our work is largely complementary rather than competitive or redundant.
For example, TGMI is building the Gene Disease Map. The GDM is a top-level, broad curation of all 20,000 genes to establish which are disease-causing. TGMI is not doing detailed individual curations of the phenotypes that are caused by these genes. Rather, we want to link out to the groups that are doing these very detailed phenotypic curations, such as ClinGen and Orphanet. The GDM will provide the overarching landscape of disease-causing genes that we hope will help other groups structure their curations.
The target audience is also different for different curation initiatives. For example the Genetics Home Reference (GHR) aims to provide easy-to-read genetic information for the general public whereas DDG2P and PanelApp are targeted at the scientific and medical community.
Interoperability is crucial
It is important that people using different curation initiatives can readily understand which things are the same. At the most fundamental level a disease-causing gene should be coded as such in every initiative, even if the nature of the coding system is different. For well-established disease-causing genes, such as CFTR – the gene that causes cystic fibrosis, this should be straight-forward. But for newer genes, and for more controversial disease-genes associations we have found there is less consistency. One of the key aims of the GenCC is to bring clarity, transparency and more consistency to how we are evaluating evidence of gene-disease links.
Using consistent terms
The second area the GenCC is working on is in using the same terms to describe the same things. There are lots of examples in genetic medicine today of different terms being used to describe the same thing, as we have highlighted in multiple blogs. Sometimes this is because we have not yet established a good system for describing something. This is true for how genes cause disease, the so-called ‘mechanism of pathogenicity’. We don’t yet have an agreed framework for classifying this or for describing it. The GenCC will be combining their expertise to address this.
Correcting gene-disease misinformation
The third topic that GenCC will focus on is in correcting misinformation about gene-disease curations. The published literature is littered with errors and misinformation about gene-disease links. This is partly because our knowledge has improved over the years. In particular, we now know rare genetic variants, including variants that affect gene functions, are normal and present in everyone. Before this was known it was assumed that a rare genetic variant had caused a person’s disease more often than was appropriate. Unfortunately, many of these incorrect assumptions are still in the system and are leading to errors in clinical testing and diagnosis.
Together the GenCC will be looking at the different types of gene-disease association errors and integrating our expertise and evidence to set the record straight.
Stronger together and stronger apart
A coalition is defined as a ‘temporary alliance for combined action’. The Gene Curation Coalition has come together to use our combined experience, resources and communities to tackle some key needs in genetic medicine today. This will also enhance the valuable work that each initiatives is undertaking separately.