Clinical Genetics

Model System Genomics

Driven by the rapid evolution of Next-Generation Sequencing, an explosive amount of genetic variants are being uncovered. To aid the identification of pathogenic variants herein, model systems have an instrumental role. Zebrafish are elegant model systems for functional genetics due to their reproductive capacity, external fertilization and development, optical transparency and amenability to genetic modification. Besides the use of zebrafish for functional genomics, we are also using this model to answer fundamental questions.

The aim of this program is to make use of genome-modifying technologies in zebrafish to:

  • characterize disease-causing genetic variants
  • understand pathophysiology using genetic disease models
  • screen for novel therapeutic approaches

Our focus is on, but not restricted to neurological diseases (small-fiber neuropathy). We are also working on disease models in cardiogenetics and metabolic diseases (galactosemia and mitochondrial disorders).

Key publications

Gerards M, Kamps R, Vanoevelen J, Boesten I, Jongen E, de Koning B, Scholte HR, de Angst I, Schoonderwoerd K, Sefiani A, Ratbi I, Coppieters W, Karim L, de Coo R, van den Bosch B, Smeets H. Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome. Brain. 2013; 136: 882-90.

Vanoevelen J, Janssens A, Huitema LF, Hammond CL, Metz JR, Flik G, Voets T, Schulte-Merker S. Trpv5/6 is vital for epithelial calcium uptake and bone formation. FASEB J. 2011; 25(9): 3197-207.

Baron S, Vangheluwe P, Sepúlveda MR, Wuytack F, Raeymaekers L, Vanoevelen J. The secretory pathway Ca2+-ATPase 1 is associated with cholesterol-rich microdomains of human colon adenocarcinoma cells. Biochim Biophys Acta. 2010; 1798(8): 1512-21.

Vangheluwe P, Sepúlveda MR, Missiaen L, Raeymaekers L, Wuytack F, Vanoevelen J. Intracellular Ca2+- and Mn2+-transport ATPases. Chem Rev. 2009; 109(10): 4733-59.

Vanoevelen J, Dode L, Van Baelen K, Fairclough RJ, Missiaen L, Raeymaekers L, Wuytack F. The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi-localized pump with high affinity for Ca2+ ions. J Biol Chem. 2005; 280(24): 22800-8.

Team leader

Jo Vanoevelen, PhD
E: j.vanoevelen@maastrichtuniversity.nl

People involved

Prof. Bert Smeets, PhD (co-investigator), Karin Faber, PhD (co-investigator), Estela Rubio, PhD (co-investigator), Arthur van de Wijngaard, PhD (co-investigator), Ivo Eijkenboom (PhD student), Rick Kamps (PhD student, shared with Bert Smeets), Britt van Erven (PhD student shared with Estela Rubio), Ana Coelho (postdoc, shared with Estela Rubio), Ellen Lambrichs (research technician), Janine Grashorn (research technician)

Funding

FP7-HEALTH-2013-INNOVATION-1: Probing The Role Of Sodium Channels In Painful Neuropathies (ProPaNe)
EMZ - Pediatrics: MetaKids

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