A5021991225- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genetic Syndromes and Imprinting
- Single-cell and spatial transcriptomics
- Reproductive System and Pregnancy
- Reproductive Biology and Fertility
- Endometriosis Research and Treatment
- Cancer Cells and Metastasis
- Fetal and Pediatric Neurological Disorders
- Assisted Reproductive Technology and Twin Pregnancy
- Gynecological conditions and treatments
- Genomics and Rare Diseases
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- Renal and related cancers
- Pregnancy and preeclampsia studies
- Ethics and Legal Issues in Pediatric Healthcare
- Molecular Biology Techniques and Applications
- Law, AI, and Intellectual Property
- Artificial Intelligence in Healthcare and Education
Maastricht University
2018-2024
Karolinska University Hospital
2023-2024
Karolinska Institutet
2023-2024
Maastricht University Medical Centre
2019-2024
University Medical Center Utrecht
2023
University Medical Center
2022
Erasmus MC
2022
KU Leuven
2012-2020
VIB-KU Leuven Center for Cancer Biology
2015
Wellcome Sanger Institute
2013
The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations cells, the genetic composition individual cells lost, de novo mutations in are concealed within bulk signal per cell cycle rates mechanisms remain elusive. Although single-cell analyses could resolve these problems, such error-prone because whole-genome amplification (WGA) artefacts limited types that can be discerned. We developed for paired-end analysis WGA products enable (i)...
Large-scale analysis of balanced chromosomal translocation breakpoints has shown nonhomologous end joining and microhomology-mediated repair to be the main drivers interchromosomal structural aberrations. Breakpoint sequences de novo unbalanced translocations have not yet been investigated systematically. We analyzed 12 mapped in nine. Surprisingly, contrast translocations, we identify nonallelic homologous recombination (NAHR) between (retro)transposable elements especially long...
Dramatic genome dynamics, such as chromosome instability, contribute to the remarkable genomic heterogeneity among blastomeres comprising a single embryo during human preimplantation development. This heterogeneity, when compatible with life, manifests constitutional mosaicism, chimerism, and mixoploidy in live-born individuals. Chimerism are defined by presence of cell lineages different parental genomes or ploidy states individual, respectively. Our knowledge their mechanistic origin...
Is the rate and nature of chromosome instability (CIN) similar between bovine in vivo-derived vitro-cultured cleavage-stage embryos? There is a major difference regarding stability embryos, as CIN significantly lower embryos compared to embryos. common during vitro embryogenesis associated with early embryonic loss humans, but vivo-conceived remains largely unknown. Because human vivo preimplantation are not accessible, (Bos taurus) were used study vivo. Five young, healthy, cycling Holstein...
Noninvasive prenatal testing (NIPT) for fetal aneuploidy screening using cell-free DNA derived from maternal plasma can incidentally raise suspicion cancer. Diagnostic routing after malignancy suspicious-NIPT faces many challenges. Here, we detail cases, and describe the clinical characteristics, chromosomal aberrations, diagnostic of patients with a confirmed malignancy. Clinical lessons be learned our experience.Patients NIPT results indicative referred tumor between April 2017 2020 were...
Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence these and allocation (ab)normal cells in embryonic placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses found that roughly half (50.4%) products conception (POCs) were karyotypically abnormal, with maternal paternal age independently contributing to increased genomic aberration rate. We applied genome haplarithmisis a subset...
Single-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt visceral metastases. The molecular nature DTCs remains elusive, as well when from where they originate. Here, we apply single-cell sequencing identify trace origin breast cancer. We sequence genomes 63 single isolated six non-metastatic cancer patients. By comparing cells' DNA copy number aberration (CNA) landscapes...
Can genome-wide haplotyping increase success following preimplantation genetic testing for a monogenic disorder (PGT-M) by including zygotes with absence of pronuclei (0PN) or the presence only one pronucleus (1PN)?Genome-wide 0PNs and 1PNs increases number PGT-M cycles reaching embryo transfer (ET) 81% live-birth rate 75%.Although significant subset 0PN 1PN can develop into balanced, diploid developmentally competent embryos, they are usually discarded because parental diploidy detection is...
Abstract STUDY QUESTION Can reduced representation genome sequencing offer an alternative to single nucleotide polymorphism (SNP) arrays as a generic and genome-wide approach for comprehensive preimplantation genetic testing monogenic disorders (PGT-M), aneuploidy (PGT-A) structural rearrangements (PGT-SR) in human embryo biopsy samples? SUMMARY ANSWER Reduced sequencing, with OnePGT, offers generic, next-generation sequencing-based automated haplotyping copy-number assessment, both combined...
Abstract Single-cell whole-genome haplotyping allows simultaneous detection of haplotypes associated with monogenic diseases, chromosome copy-numbering and subsequently, has revealed mosaicism in embryos embryonic stem cells. Methods, such as karyomapping haplarithmisis, were deployed a generic genome-wide approach for preimplantation genetic testing (PGT) are replacing traditional PGT methods. While current methods primarily rely on single-nucleotide polymorphism (SNP) array, we envision...
Abstract STUDY QUESTION Can generative artificial intelligence (AI) models produce high-fidelity images of human blastocysts? SUMMARY ANSWER Generative AI exhibit the capability to generate blastocyst images, thereby providing substantial training datasets crucial for development robust models. WHAT IS KNOWN ALREADY The integration into IVF procedures holds potential enhance objectivity and automate embryo selection transfer. However, effectiveness is limited by data scarcity ethical...
High-throughput sequencing technologies have increasingly led to discovery of disease-causing genetic variants, primarily in postnatal multi-cell DNA samples. However, applying these preimplantation testing (PGT) nuclear or mitochondrial from single few-cells biopsied vitro fertilised (IVF) embryos is challenging. PGT aims select IVF without abnormalities. Although genotyping-by-sequencing (GBS)-based haplotyping methods enabled for monogenic disorders (PGT-M), structural rearrangements...
Single-cell genomics is revolutionizing basic genome research and clinical genetic diagnosis. However, none of the current or methods for single-cell analysis distinguishes between a cell in G1-, S- G2/M-phase cycle. Here, we demonstrate by means array comparative genomic hybridization that charting DNA copy number landscape S-phase requires conceptually different approaches to G1- G2/M-phase. Remarkably, despite whole-genome amplification artifacts, log2 intensity ratios single cells...
Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% affected offspring as consequence. Until recently, comprehensive preconception carrier testing (PCT) AR disorders was unavailable in routine diagnostics. Here we developed and implemented such test clinical care.We performed exome sequencing (ES) 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic were selected. These...
Abstract Introduction Implantation failure after transferring morphologically “good‐quality” embryos in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) may be explained by impaired endometrial receptivity. Analyzing the transcriptome analysis reveal underlying processes and could help guiding prognosis using targeted interventions for infertility. This exploratory study investigated whether profile was associated with short‐term or long‐term implantation outcomes (ie success...
Abstract STUDY QUESTION What changes occur in the endometrium during aging, and do they impact fertility? SUMMARY ANSWER Both transcriptome cellular composition of endometrial samples from women advanced maternal age (AMA) are significantly different that young women, suggesting specific epithelial cells may affect receptivity. WHAT IS KNOWN ALREADY Aging is associated with accumulation senescent aging tissues. Reproductive mostly attributed to decline ovarian reserve oocyte quality, whereas...
How to select and prioritize embryos during PGD following genome-wide haplotyping?In addition genetic disease-specific information, the embryo selected for transfer is based on ranking criteria including existence of mitotic and/or meiotic aneuploidies, but not carriership mutations causing recessive disorders.Embryo selection monogenic diseases has been mainly performed using targeted assays. Recently, these approaches are being complemented by generic analysis methods such as karyomapping...
Preimplantation genetic testing (PGT) is a reproductive technology that selects embryos without (familial) variants. PGT has been applied in inherited cardiac disease and included the latest American Heart Association/American College of Cardiology guidelines. However, guidelines selecting eligible couples who will have strongest risk reduction most from are lacking. We developed an objective decision model to select eligibility for compared its results with those multidisciplinary team. All...
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects the skin and nervous system. The condition completely penetrant with extreme clinical variability, resulting in unpredictable manifestations affected offspring, complicating reproductive decision-making. One of options to prevent birth offspring preimplantation genetic testing (PGT). We performed a retrospective review medical files all couples (n = 140) referred Dutch PGT expert center indication NF1 between...