Introduction: Chronic kidney disease (CKD), defined as a diminished glomerular filtration rate or presence of impaired renal function markers for at least 3 months, is associated with a high risk to develop chronic end stage kidney failure which still have limited therapeutic options like dialysis or kidney transplantation. This thesis aims to identify new molecular and cellular markers linked with CKD and its complications including fibrosis. Methods: Next generation sequencing will be applied to identify genetic factors associated with hereditary nephropathies such as nephronophthisis (NPHP). Results: We demonstrate the utility of whole-genome sequencing (WGS) for the molecular diagnosis of NPHP by identifying two putative disease-causing intronic mutations in the NPHP3 gene, including one deep intronic variant. We further show that both intronic variants, by affecting splicing, result in a truncated nephrocystin-3 protein. Conclusion: This study provides a framework for applying WGS as a first-line diagnostic tool for highly heterogeneous disease such as NPHP and further suggests that deep intronic variations are an important underestimated cause of monogenic disorders.