Do you have a list of genomic intervals or a list of SNPs in the human genome?
Great, MendelVar can help you discover any genes associated with highly penetrant monogenic/oligogenic Mendelian diseases in your regions of interest.
Secondly, MendelVar will list rare pathogenic mutations overlapping the regions of interest which are causal for those Mendelian disorders.
Lastly, MendelVar tests for enrichment of disease and human phenotype ontology terms among the discovered Mendelian genes relative to the background of all Mendelian genes across the genome. This can reveal what anatomical entities, symptoms and organ systems are overrepresented among disease linked to causal genes residing in your regions of interest.
MendelVar webserver's goal is testing for enrichment of human phenotype and disease ontology terms amongst genes linked to Mendelian disorders situated within a list of custom genomic intervals. MendelVar provides a quick overview of possible impact of Mendelian disease-related genes on user's complex phenotype of interest. It returns the details of all known broadly defined Mendelian diseases and their causal genes found in the custom genomic intervals as well as overlapping pathogenic rare mutations responsible for Mendelian disease. Enrichment of Disease Ontology, Human Phenotype Ontology terms among the Mendelian genes gives the researcher an overview of any shared features with their trait of interest, e.g. in terms of anatomy.
We envisage MendelVar will be especially useful for post-GWAS annotation. MendelVar adds a useful step in triangulating genetic evidence when prioritising candidate causal genes in a complex phenotype, so called in silico fine mapping. The number of genes with a known disruption resulting in Mendelian disorder currently totals ~4,500 genes and ~300 new Mendelian phenotypes are discovered every year. It has been hypothesised that subtle dysregulation of these gene's function, mainly through regulatory changes affecting expression, can contribute to risk for phenotypically similar complex disease. Recently, Freund et al. (2018) have shown that genes with confirmed phenotypically-matching Mendelian lesions are enriched for among closest GWAS genes across 62 human traits.
Knowledge that:
can strengthen the case for importance of these GWAS genes in contributing to the complex trait.