A5020260568- Epigenetics and DNA Methylation
- Congenital heart defects research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Retinal Development and Disorders
- Genomics and Chromatin Dynamics
- Digestive system and related health
- RNA regulation and disease
- Protist diversity and phylogeny
- Birth, Development, and Health
- RNA Research and Splicing
- Hearing, Cochlea, Tinnitus, Genetics
- Chromosomal and Genetic Variations
- Developmental Biology and Gene Regulation
- Ocular Disorders and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Single-cell and spatial transcriptomics
Radboud University Nijmegen
2016-2023
Radboud University Medical Center
2016-2023
University Medical Center
2019-2022
Radboud Institute for Molecular Life Sciences
2016-2019
The cause of autosomal-dominant retinitis pigmentosa (adRP), which leads to loss vision and blindness, was investigated in families lacking a molecular diagnosis. A refined locus for adRP on Chr17q22 (RP17) delineated through genotyping genome sequencing, leading the identification structural variants (SVs) that segregate with disease. Eight different complex SVs were characterized 22 adRP-affected >300 affected individuals. All RP17 had breakpoints within genomic region spanning YPEL2...
A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected
Abstract Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer zeste homolog 2 (Ezh2), the PcG protein responsible for placing repressive H3K27me3 mark. identified a nonsense mutant ezh2 and generated maternal zygotic (MZ) embryos. In contrast knockout mice proteins, MZezh2 embryos gastrulate seemingly normal, but die around days post fertilization displaying...
Abstract The Polycomb group (PcG) protein family is a well-known of epigenetic modifiers. We used zebrafish to investigate the role Rnf2, enzymatic subunit PRC1. found positive correlation between loss Rnf2 and upregulation genes, especially those whose promoter normally bound by Rnf2. heart rnf2 mutants shows tubular shaped morphology further understand underlying mechanism, we studied gene expression single wildtype mutant hearts. detected most pronounced differences at 3 dpf, including...
Many regulatory pathways are conserved in the zebrafish intestine compared to mammals, rendering it a strong model study intestinal development. However, (epi)genetic regulation of development remains largely uncharacterized. We performed RNA-sequencing and chromatin immunoprecipitation (ChIP)-sequencing for activating (H3K4me3) repressive (H3K27me3) marks on isolated intestines at 5, 7, 9 days post-fertilization (dpf), during which transit from yolk dependence external feeding. showed...
ABSTRACT Polycomb group (PcG) proteins are transcriptional repressors that important regulators of cell fate during embryonic development. Among them, Ezh2 is responsible for catalyzing the epigenetic repressive mark H3K27me3 and essential animal The ability zebrafish embryos lacking both maternal zygotic ezh2 to form a normal body plan provides unique model comprehensively studying function early development in vertebrates. By using multi-omics approach, we found required deposition proper...
CRISPR-Cas9-based genome-editing is a highly efficient and cost-effective method to generate zebrafish loss-of-function alleles. However, introducing patient-specific variants into the genome with CRISPR-Cas9 remains challenging. Targeting options can be limited by predetermined genetic context, efficiency of homology-directed DNA repair pathway relatively low. Here, we illustrate our approach develop knock-in models using two previously associated hereditary sensory deficits. We employ...
Polycomb group (PcG) proteins are essential regulators of epigenetic gene silencing and development. The PcG protein enhancer zeste homolog 2 (Ezh2) is a key component the Repressive Complex responsible for placing histone H3 lysine 27 trimethylation (H3K27me3) repressive mark on genome through its methyltransferase domain. Ezh2 highly conserved in vertebrates. We studied role ezh2 during development zebrafish with use mutant allele (ezh2(sa1199), R18STOP), which has stop mutation second...
A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete USH2A screening in the early days testing. These cases lack eligibility for optimal counseling and future therapy. defects are most frequent cause USH2 also causative individuals arRP. Therefore, is an important target screening. The aim this study was assess unscreened incompletely screened unexplained arRP (likely) pathogenic...
The USH2A variant c.2276 G > T (p.(Cys759Phe)) has been described by many authors as a frequent cause of autosomal recessive retinitis pigmentosa (arRP). However, this is in contrast with the description two asymptomatic individuals homozygous for variant. We therefore assessed pathogenicity using extensive genetic and functional analyses. Whole genome sequencing optical mapping were performed three arRP cases to exclude alternative causes. A minigene splice assay was designed investigate...
Non-canonical splice site variants are increasingly recognized as a relevant cause of the USH2A-associated diseases, non-syndromic autosomal recessive retinitis pigmentosa and Usher syndrome type 2. Many non-canonical have been reported in public databases, but an effect on pre-mRNA splicing has only functionally verified for subset these variants. In this study, we aimed to extend knowledge regarding events by assessing selected set USH2A study their potential pathogenicity. Eleven were...
ABSTRACT Epigenetic data obtained from whole zebrafish embryos or larvae may mask dilute organ-specific information. Fluorescence activated cell sorting can diverge cells their native state, and cryosections often yield insufficient material for molecular analysis. Here, we present a reproducible method larval intestinal isolation at 5, 7, 9 days post-fertilization, using the intestine-specific transgene tgBAC(cldn15la:GFP) . With tweezers, intestine be pulled out of abdomen in one smooth...
Abstract Polycomb group (PcG) proteins are transcriptional repressors that important regulators of cell fate during embryonic development. Among them, Ezh2 is responsible for catalyzing the epigenetic repressive mark H3K27me3 and essential animal The ability zebrafish embryos lacking both maternal zygotic ezh2 to form a normal body plan provides unique model comprehensively study function early development in vertebrates. By using multi-omics approach, we found required deposition...