Next Generation Sequencing and phenotyping

Phenotyping and next generation sequencing for the identification of gene variants associated with human diseases

Our aim is to identify novel associations between highly penetrant gene variants and human phenotypes. Disease associated gene variants may serve as the starting point to unravel molecular pathways and targets for therapeutic interventions. We focus mainly on heritable disorders of the central nervous system as well as a few other phenotypes. Disorders caused single, high penetrant genes (i.e. Mendelian or monogenic disorders) are extremely heterogeneous and they affect approximately 5% of the population in Western societies. The approximately 8,000 Mendelian entities described to date constitute a major socioeconomic burden worldwide. The identification of causative gene variants is crucial not only for our understanding of developmental processes, organ function and development of novel therapies, but also for accurate diagnosis, appropriate follow-up and counseling to patients/families. We apply whole genome sequencing, whole exome sequencing, targeted resequencing and transcriptome sequencing (Illumina and Ion Proton sequencing platforms) on samples from selected patients/families/cohorts. To date, we have characterized the genetic causes of a number of unique phenotypes/disorders and additional clinical entities are continuously identified through Uppsala University Hospital as well as through national and international collaborators. The identification of novel gene variants/genes causing Mendelian traits are further examined and validated in different biological systems, e.g. induced pluripotent stem cells (iPSC), to recapitulate pathophysiology and disease mechanisms.