Papers by Joris Vermeesch
Cytogenetic and Genome Research, 2004
Small supernumerary marker chromosomes (sSMC), defined as additional centric chromosome fragments... more Small supernumerary marker chromosomes (sSMC), defined as additional centric chromosome fragments too small to be identified or characterized unambiguously by banding cytogenetics alone, are present in 0.043% of newborn children. Several attempts have been made to correlate certain sSMC with a specific clinical picture, resulting in the description of several syndromes such as the i(18p)-, der(22)-, i(12p)- (Pallister Killian syndrome) and inv dup(22)- (cat-eye) syndromes. However, most of the remaining sSMC including minute-, ring-, inverted-duplication- as well as complex-rearranged chromosomes, have not yet been correlated with clinical syndromes, mostly due to problems in their comprehensive characterization. Here we present an overview of sSMC, including the first attempt to address problems of nomenclature and their modes of formation, problems connected with mosaicism plus familial occurrence. The review also discusses the frequency of sSMC in prenatal, postnatal, and clinica...
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European journal of human genetics : EJHG, Jan 3, 2015
In 2013, the American College of Medical Genetics (ACMG) examined the issue of incidental finding... more In 2013, the American College of Medical Genetics (ACMG) examined the issue of incidental findings in whole exome and whole genome sequencing, and introduced recommendations to search for, evaluate and report medically actionable variants in a set of 56 genes. At a debate held during the 2014 European Society for Human Genetics Conference (ESHG) in Milan, Italy, the first author of that paper presented this view in a debate session that did not end with a conclusive vote from the mainly European audience for or against reporting back actionable incidental findings. In this meeting report, we elaborate on the discussions held during a special meeting hosted at the ESHG in 2013 from posing the question 'How to reach a (European) consensus on reporting incidental findings and unclassified variants in diagnostic next generation sequencing'. We ask whether an European consensus exists on the reporting of incidental findings in genome diagnostics, and present a series of key issue...
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Molecular Cytogenetics, 2009
Background Small supernumerary marker chromosomes (sSMC) can be present in numerically abnormal k... more Background Small supernumerary marker chromosomes (sSMC) can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar. Results Here we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT) derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14)(q11.1). The present case is the third Turner syndrome case with an sSMCT not derived from the X- or the Y-chromosome. Conclusion More comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data.
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Reproductive Health and Human Rights, 2003
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Genome Biology
Background During normal zygotic division, two haploid parental genomes replicate, unite and segr... more Background During normal zygotic division, two haploid parental genomes replicate, unite and segregate into two biparental diploid blastomeres. Results Contrary to this fundamental biological tenet, we demonstrate here that parental genomes can segregate to distinct blastomeres during the zygotic division resulting in haploid or uniparental diploid and polyploid cells, a phenomenon coined heterogoneic division. By mapping the genomic landscape of 82 blastomeres from 25 bovine zygotes, we show that multipolar zygotic division is a tell-tale of whole-genome segregation errors. Based on the haplotypes and live-imaging of zygotic divisions, we demonstrate that various combinations of androgenetic, gynogenetic, diploid, and polyploid blastomeres arise via distinct parental genome segregation errors including the formation of additional paternal, private parental, or tripolar spindles, or by extrusion of paternal genomes. Hence, we provide evidence that private parental spindles, if faili...
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Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 → qte... more Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31 → qter) detected in an autistic boy
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Microarray analysis enables the genome-wide detection of copy number variations and the investiga... more Microarray analysis enables the genome-wide detection of copy number variations and the investigation of chromosomal instability. Whereas array techniques have been well established for the analysis of unamplified DNA derived from many cells, it has been more challenging to enable the accurate analysis of single cell genomes. In this review, we provide an overview of single cell DNA amplification techniques, the different array approaches, and discuss their potential applications to study human embryos.
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npj Genomic Medicine, 2021
Chromosome instability is inherent to human IVF embryos, but the full spectrum and developmental ... more Chromosome instability is inherent to human IVF embryos, but the full spectrum and developmental fate of chromosome anomalies remain uncharacterized. Using haplotyping-based preimplantation genetic testing for monogenic diseases (PGT-M), we mapped the parental and mechanistic origin of common and rare genomic abnormalities in 2300 cleavage stage and 361 trophectoderm biopsies. We show that while single whole chromosome aneuploidy arises due to chromosome-specific meiotic errors in the oocyte, segmental imbalances predominantly affect paternal chromosomes, implicating sperm DNA damage in segmental aneuploidy formation. We also show that postzygotic aneuploidy affects multiple chromosomes across the genome and does not discriminate between parental homologs. In addition, 6% of cleavage stage embryos demonstrated signatures of tripolar cell division with excessive chromosome loss, however hypodiploid blastomeres can be excluded from further embryo development. This observation supports...
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Reproduction, 2020
While chromosomal mosaicism in the embryo was observed already in the 1990s using both karyotypin... more While chromosomal mosaicism in the embryo was observed already in the 1990s using both karyotyping and FISH technologies, the full extent of this phenomenon and the overall awareness of the consequences of chromosomal instability on embryo development has only come with the advent of sophisticated single-cell technologies. High-throughput techniques, such as DNA microarrays and massive parallel sequencing, have shifted single-cell genome research from evaluating a few loci at a time to the ability to perform comprehensive screening of all 24 chromosomes. The development of genome-wide single-cell haplotyping methods have also enabled for simultaneous detection of single-gene disorders and aneuploidy using a single universal protocol. Today, three decades later haplotyping-based embryo testing is performed worldwide to reliably detect virtually any Mendelian hereditary disease with a known cause, including autosomal-recessive, autosomal-dominant and X-linked disorders. At the same ti...
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Nature Medicine, 2019
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Human Reproduction, 2017
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Human reproduction (Oxford, England), Mar 2, 2017
How to select and prioritize embryos during PGD following genome-wide haplotyping? In addition to... more How to select and prioritize embryos during PGD following genome-wide haplotyping? In addition to genetic disease-specific information, the embryo selected for transfer is based on ranking criteria including the existence of mitotic and/or meiotic aneuploidies, but not carriership of mutations causing recessive disorders. Embryo selection for monogenic diseases has been mainly performed using targeted disease-specific assays. Recently, these targeted approaches are being complemented by generic genome-wide genetic analysis methods such as karyomapping or haplarithmisis, which are based on genomic haplotype reconstruction of cell(s) biopsied from embryos. This provides not only information about the inheritance of Mendelian disease alleles but also about numerical and structural chromosome anomalies and haplotypes genome-wide. Reflections on how to use this information in the diagnostic laboratory are lacking. We present the results of the first 101 PGD cycles (373 embryos) using hap...
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Genome Research, 2016
Dramatic genome dynamics, such as chromosome instability, contribute to the remarkable genomic he... more Dramatic genome dynamics, such as chromosome instability, contribute to the remarkable genomic heterogeneity among the blastomeres comprising a single embryo during human preimplantation development. This heterogeneity, when compatible with life, manifests as constitutional mosaicism, chimerism, and mixoploidy in live-born individuals. Chimerism and mixoploidy are defined by the presence of cell lineages with different parental genomes or different ploidy states in a single individual, respectively. Our knowledge of their mechanistic origin results from indirect observations, often when the cell lineages have been subject to rigorous selective pressure during development. Here, we applied haplarithmisis to infer the haplotypes and the copy number of parental genomes in 116 single blastomeres comprising entire preimplantation bovine embryos (n = 23) following in vitro fertilization. We not only demonstrate that chromosome instability is conserved between bovine and human cleavage emb...
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The American Journal of Human Genetics, 2015
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Frontiers in genetics, 2012
Microarray analysis enables the genome-wide detection of copy number variations and the investiga... more Microarray analysis enables the genome-wide detection of copy number variations and the investigation of chromosomal instability. Whereas array techniques have been well established for the analysis of unamplified DNA derived from many cells, it has been more challenging to enable the accurate analysis of single cell genomes. In this review, we provide an overview of single cell DNA amplification techniques, the different array approaches, and discuss their potential applications to study human embryos.
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Genome biology, Jan 29, 2011
Detection of chromosomal aberrations from a single cell by array comparative genomic hybridizatio... more Detection of chromosomal aberrations from a single cell by array comparative genomic hybridization (single-cell array CGH), instead of from a population of cells, is an emerging technique. However, such detection is challenging because of the genome artifacts and the DNA amplification process inherent to the single cell approach. Current normalization algorithms result in inaccurate aberration detection for single-cell data. We propose a normalization method based on channel, genome composition and recurrent genome artifact corrections. We demonstrate that the proposed channel clone normalization significantly improves the copy number variation detection in both simulated and real single-cell array CGH data.
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Molecular Cytogenetics, 2014
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Nucleic Acids Research, 2013
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Nucleic Acids Research, 2006
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Molecular Cytogenetics, 2009
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Papers by Joris Vermeesch