Department of Human Genetics

Inselspital Bern

The subject of research in human genetics is the genetic basis of diseases. Research at the Department of Human Genetics focuses on elucidating and understanding the molecular basis of mainly monogenic diseases and the clinical characterization of disease patterns and genotype-phenotype correlations.

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Director and Chief Physician

Prof. Dr. Dr. med. Christiane Zweier

Profile

  • Teaching students of medicine and biology
  • Providing training in Medical Genetics (FMH and FAMH)
  • Offering PhD training in programs of the Graduate Schools of the University of Bern
  • Two research groups
  • Identification of new disease genes for neurodevelopmental, mitochondrial and rare disorders
  • Clinical and mutational characterization of neurodevelopmental, mitochondrial and rare disorders
  • Drosophila melanogaster as a model organism to functionally characterize disease mechanisms and to investigate genetic interactions
  • iPSC and other cell-based models to investigate pathomechanisms

External Partners

Department of Medical Genetics, University Hospital Basel; Institute of Medical Genetics, University Zürich; Institute of Human Genetics, University Hospital Erlangen; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics; SwissITHACA network; ERN ITHACA; multiple international clinical/genetic collaborators

Grants

  • Novartis Foundation for medical-biological Research, #22C194, 2023-2024 (Zweier)
  • BCPM lighthouse project, PACE, 2024-2026 (Zweier)
  • SNSF, project 10001220, 2024-2028 (Zweier)

Highlights 2025

Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency

In this work we elucidated pathomechanisms underlying FBXO11-related neurodevelopmental disorder. Using the fruit fly and human neurons as model systems, we showed that loss of FBXO11 impairs important processes of neuronal development. Activation of the proteasome using the long-approved drug Verapamil among others ameliorated and reversed observed neuronal phenotypes, opening a new avenue for therapeutic development through drug repurposing for this rare disorder.

Gregor at al., HGG Adv. 2025

Patch clamp recordings in iPSC derived neurons

Deregulated ion channels contribute to RHOBTB2-associated developmental and epileptic encephalopathy

Through transcriptome analysis and genetic interaction studies in Drosophila, we found evidence for deregulation of ion channels in RHOBTB2-related developmental and epileptic encephalopathy due to BTB domain missense variants. We observed altered electrophysiological behavior of hiPSC derived neurons with patient-specific, heterozygous missense variants in the BTB domains, but not for missense variants in the GTPase domain or complete loss, which are associated with milder and more variable neurodevelopmental phenotypes. These differences might contribute to the genotype-phenotype correlations observed regarding location, nature and zygosity of RHOBTB2 variants.

Langhammer et al., Hum Mol Genet. 2025

Scratch assay with neuron-like cells

Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology

By trio exome sequencing and international collaboration, we identified (de novo) truncating variants in SRRM1, encoding a key component of spliceosomes and for mRNA processing, in three individuals with variable neurodevelopmental phenotypes. Knockdown of SRRM1 in SKNBE2 cells by CRISPR/Cas9 editing and subsequent differentiation into neuron like cells resulted in impaired cell proliferation, migration, and neurite outgrowth. Furthermore, pan-neuronal or motoneuronal knockdown of the orthologue Srrm1 in Drosophila lead to reduced viability or impaired gross neurological function, respectively. Taken together, our observations support SRRM1 as a candidate gene for Neurodevelopmental Disorders.

Altay et al., Eur J Hum Genet. 2025