Diagnostics of genetic disorders with whole genome and mRNA sequencingBergant, Gaber (Avtor) Peterlin, Borut (Mentor) genetic diagnosticsgenome sequencingnext-generation sequencingrare diseaseRNA sequencingDespite the widespread use of exome sequencing (ES), over 60% of patients with suspected genetic diseases remain undiagnosed. Additionally, the precise genetic cause of many rare diseases remains obscure. This study addresses these two challenges using genome sequencing (GS) in patients with suspected diverse genetic diseases and RNA sequencing in patients with suspected hereditary myopathies. In this study we tested two hypotheses: (1) GS and RNA sequencing improve the diagnostic yield of genetic diagnostics and (2) enable the discovery of potential new disease mechanisms and genes previously not yet associated with genetic diseases. Employing GS and RNA sequencing, we achieved a diagnostic yield of 12.5% (16/128 patients) and 18.2% (2/11 patients) in previously negative ES patients, respectively. Additionally, both methods detected variants that could not be detected by ES. We also identified five candidate genes for new genetic diseases, which we thoroughly investigated, and one genetic variant which we propose causes the disease through a novel mechanism. Our results confirm both of our initial hypotheses and contribute significantly to progress in human genetics. Furthermore, our study lays a solid foundation for future research aimed at applying comprehensive diagnostic methods to some of the most challenging cases in clinical genetics.20252025-03-18 07:15:13Doktorsko delo/naloga167864VisID: 30513COBISS_ID: 229332483sl