A5009367933- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Fetal and Pediatric Neurological Disorders
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Parvovirus B19 Infection Studies
- Molecular Biology Techniques and Applications
- Genomics and Phylogenetic Studies
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Genomics and Rare Diseases
- Single-cell and spatial transcriptomics
- Plant Molecular Biology Research
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cell Image Analysis Techniques
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Colorectal Cancer Treatments and Studies
- Plant Virus Research Studies
- Dysphagia Assessment and Management
- Neurogenetic and Muscular Disorders Research
- Genetics and Neurodevelopmental Disorders
- Chronic Lymphocytic Leukemia Research
Oncode Institute
2019-2025
University Medical Center Utrecht
2017-2025
Utrecht University
2017-2024
Vrije Universiteit Amsterdam
2020
Amsterdam University Medical Centers
2013-2020
Heidelberg University
2020
University Hospital Heidelberg
2020
Amsterdam UMC Location VUmc
2013-2018
Delft University of Technology
2014
Abstract Genetic disorders can be detected by prenatal diagnosis using Chorionic Villus Sampling, but the 1:100 chance to result in miscarriage restricts use fetuses that are suspected have an aberration. Detection of trisomy 21 cases noninvasively is now possible owing upswing next-generation sequencing (NGS) because a small percentage fetal DNA present maternal plasma. However, detecting other trisomies and smaller aberrations only realized high-coverage NGS, making it too expensive for...
Noninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, clinical significance of these aberrations found pregnancies at risk trisomy or Whole-genome shallow massively parallel sequencing was used all autosomes were analyzed. In 78 2,527 cases (3.1%) NIPS indicative 13, 41 (1.6%) aberrations....
Abstract Objective While large fetal copy number aberrations can generally be detected through sequencing of DNA in maternal blood, the reliability tests depends on fraction that originates from fetus. Existing methods to determine this require additional work or are limited male fetuses. We aimed create a sex‐independent approach without work. Methods fragments used for noninvasive prenatal testing cut only by natural processes; thus, influences cutting packaging nucleosomes will preserved...
Abstract Genomic DNA is constantly subjected to oxidative damage, which thought be one of the major drivers cancer and age-dependent decline. The most prominent consequence modification guanine into 8-hydroxyguanine (8-oxo-dG), has important mutagenic potential plays a role in methylation-mediated gene regulation. Methods simultaneously detect quantify 8-oxo-dG within its genomic context have been lacking; mainly because these methods rely on indirect detection or are based hydrolysis DNA....
To compare available analysis methods for determining fetal fraction on single read next generation sequencing data. This is important as the performance of non-invasive prenatal testing (NIPT) procedures depends DNA.We tested six different detection in NIPT samples. The same clinically obtained data were used all methods, allowing us to assess effect test result, and investigate use quality control.We show that non-NIPT based body mass index (BMI) gestational age are unreliable predictors...
The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2, remains incompletely resolved due to numerous segmental duplications. Variation in SMN2 copy number, presumably influenced by conversion, affects disease severity, though number alone has insufficient prognostic value limited genotype–phenotype correlations. With advancements newborn screening SMN-targeted therapies, identifying genetic...
Levels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive diagnostics and monitoring. However, detecting ctDNA is challenging, much fewer than 5% the cell-free blood typically originates from tumor. To detect lowly abundant molecules based on somatic variants, extremely sequencing methods are required. Here, we describe new technique, CyclomicsSeq, which Oxford Nanopore concatenated copies single molecule. Consensus...
Tumor-specific genetic aberrations in cell-free DNA (cfDNA) from plasma are promising biomarkers for diagnosis of recurrent head and neck squamous cell carcinoma (HNSCC). However, the sensitivity when using somatic mutations only cfDNA is suboptimal. Here, we combined detection copy number (CNAs), human papillomavirus (HPV) a single sequencing workflow. Pretreatment plasmas 40 patients 20 non-cancer controls were used analysis. Plasma underwent low-coverage whole genome (lcWGS) to detect...
Abstract The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2 , remains incompletely resolved due to numerous segmental duplications. Variation in copy number, presumably influenced by conversion, affects disease severity, though number alone has insufficient prognostic value limited genotype-phenotype correlations. With advancements newborn screening SMN -targeted therapies, identifying genetic...
In clinical genetics, detection of single nucleotide polymorphisms (SNVs) as well copy number variations (CNVs) is essential for patient genotyping. Obtaining both CNV and SNV information from WES data would significantly simplify workflow. Unfortunately, the sequence reads obtained with vary between samples, complicating accurate WES. To avoid being dependent on other we developed a within-sample comparison approach (WISExome). For every (WES) target region genome, identified set reference...
Most tumors are composed of a heterogeneous population subclones. A more detailed insight into the subclonal evolution these can be helpful to study progression and treatment response. Problematically, tumor samples typically very heterogeneous, making deconvolving individual subclones major challenge. To overcome this limitation, reducing heterogeneity, such as by means microdissections, coupled with targeted sequencing, is viable approach. However, computational methods that enable...
Abstract Loss-of-function mutations in the gene encoding acetyltransferase CREBBP have been reported numerous cancers but are particularly frequent lymphoid malignancies. However, functional significance of loss transformation and disease progression, most likely through cooperation with secondary genetic hits, has not yet fully unravelled. Similarly, contribution initial cell population sustaining course remains elusive. Here, we developed a new lymphoma mouse model integrating Crebbp at...
ABSTRACT Chromatin folding is increasingly recognized as a regulator of genomic processes such gene activity. Chromosome conformation capture (3C) methods have been developed to unravel genome topology through the analysis pair-wise chromatin contacts and identified many genes regulatory sequences that, in populations cells, are engaged multiple DNA interactions. However, cannot discern whether occur simultaneously or competition on individual chromosome. We present novel 3C method,...
Abstract Background & Aims Heterozygous inactivating mutations of Liver Kinase B1 (LKB1) are causative to the Peutz-Jeghers syndrome (PJS), a hereditary disease characterized by gastrointestinal polyposis and increased cancer susceptibility. While LKB1 loss-induced polyp formation has been ascribed non-epithelial tissues, how deficiency increases risk patients altering phenotypical landscape hierarchical organization epithelial tissues remains poorly understood. Methods Using...