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 all GWAS genes across 62 human traits.
‐a given gene, out of all the genes in linkage disequilibrium (LD) with the top variant is associated with a term that is found at other GWAS loci;
‐that the term is enriched among the GWAS genes relative to background;
‐that the term refers to confirmed aspect of the disease biology: anatomical entity or symptomcan strengthen the case for importance of these GWAS genes
in contributing to the complex trait.
If you found MendelVar useful, please cite our paper:
Sobczyk MK, Gaunt TR, Paternoster L. (2020). MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes. bioRvix doi: https://doi.org/10.1101/2020.04.20.050237
For any queries, bugs and suggestions, please e-mail the lead developer
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