Project

Zebrafish as a model system to evaluate the causality of variants of unknown clinical significance in hereditary breast cancer

Code
365W9115
Duration
01 January 2015 → 31 December 2018
Funding
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other basic sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other clinical sciences
    • Other health sciences
    • Nursing
    • Other paramedical sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other translational sciences
    • Other medical and health sciences
Keywords
zebrafish
 
Project description

In hereditary breast cancer, knowledge of the genetic cause provides the opportunity to include high risk individuals in surveillance programs and may tailor therapeutics. Since the implementation of next generation sequencing in molecular diagnostics, the number of variants of unknown clinical significance (VUS) increased dramatically. The finding of such a variant creates a lot of uncertainty. Therefore, development of reliable functional assays is highly warranted. We propose zebrafish as a model system as it involved in DNA DSB repair and genome stability maintenance by the homologous recombination (HR) pathway. Several assays evaluating DNA repair capacity by HR will be optimized for application in zebrafish embryos. The functionaly of the pathway will be compared between wild type embryos, embryos in which the gene of interest is knocked-out and rescued using capped mRNAs containing the VUS to be studied.