Gene Ontology Enrichment Analysis of Renal Agenesis: Improving Prenatal Molecular Diagnosis

Uni- or bilateral renal agenesis (RA) is a commonly occurring major congenital anomaly impacting fetal and neonatal outcomes. Since the etiology is highly heterogeneous, our aim was to provide a logically structured approach by highlighting the genes in which variants have been identified to be associated with RA and to define the pathways involved in this type of abnormal kidney development. We used Phenolyzer to collect a list of all the genes known as causative for RA. Using ClueGO gene enrichment analysis, we classified the relationship between these genes and the biological processes defined by gene ontology. We identified 287 genes and 69 groups of enriched biological processes. About 50% included pathways directly related to the development of urogenital organ tissues. Several ciliary, axis specification, hindgut development, and endocrine pathways were enriched, which may relate to different clinical presentations of RA. Our gene ontology enrichment analysis shows that genes representing distinct biological pathways are significantly enriched. This knowledge will lead to an improved molecular diagnosis in clinical care when applying genome-wide sequencing approaches. The findings will also allow to further study the biological pathways involved in RA and to identify novel candidate genes and pathways.