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American Journal of Human Genetics Aug 2021Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard...
Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics. Drawbacks of these tests are a very low resolution (karyotyping) and the inability to detect balanced SVs or indicate the genomic localization and orientation of duplicated segments or insertions (copy number variant [CNV] microarrays). Here, we investigated the ability of optical genome mapping (OGM) to detect known constitutional chromosomal aberrations. Ultra-high-molecular-weight DNA was isolated from 85 blood or cultured cells and processed via OGM. A de novo genome assembly was performed followed by structural variant and CNV calling and annotation, and results were compared to known aberrations from standard-of-care tests (karyotype, FISH, and/or CNV microarray). In total, we analyzed 99 chromosomal aberrations, including seven aneuploidies, 19 deletions, 20 duplications, 34 translocations, six inversions, two insertions, six isochromosomes, one ring chromosome, and four complex rearrangements. Several of these variants encompass complex regions of the human genome involved in repeat-mediated microdeletion/microduplication syndromes. High-resolution OGM reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints. This proof-of-principle study demonstrates the ability of OGM to detect nearly all types of chromosomal aberrations. We also suggest suited filtering strategies to prioritize clinically relevant aberrations and discuss future improvements. These results highlight the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and structural variants, which could give rise to an era of "next-generation cytogenetics."
Topics: Chromosome Aberrations; Chromosome Disorders; Chromosome Mapping; Cytogenetic Analysis; DNA Copy Number Variations; Genome, Human; Humans; Karyotyping; Microarray Analysis
PubMed: 34237280
DOI: 10.1016/j.ajhg.2021.05.012 -
Frontiers in Endocrinology 2022
Topics: Humans; Reproduction; Infertility; Cytogenetic Analysis
PubMed: 36568095
DOI: 10.3389/fendo.2022.1107903 -
Clinics in Laboratory Medicine Dec 2011The myelodysplastic syndromes are a diverse group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased... (Review)
Review
The myelodysplastic syndromes are a diverse group of clonal stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenias, and an increased propensity to evolve to acute myeloid leukemia. The molecular pathogenesis of these disorders is poorly understood, but recurring chromosomal abnormalities occur in approximately 50% of cases and are the focus of much investigation. The availability of newer molecular techniques has allowed the identification of additional genetic aberrations, including mutations and epigenetic changes of prognostic and potential therapeutic importance. This review focuses on the key role of cytogenetic analysis in myelodysplastic syndromes in the context of the diagnosis, prognosis, and pathogenesis of these disorders.
Topics: Chromosome Aberrations; Cytogenetic Analysis; Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 22118747
DOI: 10.1016/j.cll.2011.08.005 -
Cytogenetic and Genome Research 2021
Topics: Chromosome Aberrations; Chromosome Banding; Cytogenetic Analysis; Cytogenetics; Humans
PubMed: 34407536
DOI: 10.1159/000516654 -
Genes Jan 2023Geckos (Gekkota), the species-rich clade of reptiles with more than 2200 currently recognized species, demonstrate a remarkable variability in diploid chromosome numbers...
Geckos (Gekkota), the species-rich clade of reptiles with more than 2200 currently recognized species, demonstrate a remarkable variability in diploid chromosome numbers (2n = 16-48) and mode of sex determination. However, only a small fraction of gekkotan species have been studied with cytogenetic methods. Here, we applied both conventional (karyotype reconstruction and C-banding) and molecular (fluorescence in situ hybridization with probes for rDNA loci and telomeric repeats) cytogenetic analyses in seven species of geckos, namely , , , cf. , , (Gekkonidae) and (Phyllodactylidae), in order to provide further insights into the evolution of karyotypes in geckos. Our analysis revealed the presence of interstitial telomeric repeats in four species, but we were not able to conclude if they are remnants of previous chromosome rearrangements or were formed by an accumulation of telomeric-like satellite motifs. Even though sex chromosomes were previously identified in several species from the genera and by cytogenetic and/or genomic methods, they were not detected by us in any examined species. Our examined species either have poorly differentiated sex chromosomes or, possibly, environmental sex determination. Future studies should explore the effect of temperature and conduct genome-wide analyses in order to identify the mode of sex determination in these species.
Topics: Animals; Lizards; In Situ Hybridization, Fluorescence; Genome-Wide Association Study; Sex Chromosomes; Karyotyping
PubMed: 36672918
DOI: 10.3390/genes14010178 -
Polish Archives of Internal Medicine Aug 2022Throughout the last 50 years, cytogenetic analyses of pretreatment bone marrow and / or blood samples from patients diagnosed with acute myeloid leukemia (AML) revealed... (Review)
Review
Throughout the last 50 years, cytogenetic analyses of pretreatment bone marrow and / or blood samples from patients diagnosed with acute myeloid leukemia (AML) revealed a large number of recurring chromosome aberrations, both structural and numerical. Using standard banding methods and, more recently, molecular cytogenetic techniques, such as fluorescence in situ hybridization, spectral karyotyping, multiplex fluorescence in situ hybridization and comparative genomic hybridization, cytogenetic investigations detect acquired abnormalities that, together with submicroscopic gene mutations and changes in gene expression, strongly influence the clinical features and prognosis of patients with AML. Selected reciprocal translocations and inversions and their molecular counterparts, as well as a number of unbalanced chromosome abnormalities are used, together with bone marrow morphology, immunophenotype, and clinical characteristics, to define separate AML entities in the World Health Organization Classification of Haematolymphoid Tumours. Moreover, cytogenetic findings (and specific gene mutations) are being used in geneticrisk classifications, such as the 2022 European LeukemiaNet classification. Such classifications divide patients into broad prognostic categories: favorable, intermediate, and adverse, which are useful in the management of adults with AML. In this article, I review the present data on recurrent chromosome rearrangements in AML and on correlations between cytogenetic findings and clinical features and treatment outcomes of adult patients diagnosed with AML.
Topics: Adult; Chromosome Aberrations; Comparative Genomic Hybridization; Cytogenetic Analysis; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute
PubMed: 35848612
DOI: 10.20452/pamw.16300 -
Cancer Genomics & Proteomics 2021A fusion gene is the physical juxtaposition of two different genes resulting in a structure consisting of the head of one gene and the tail of the other. Gene fusion is... (Review)
Review
A fusion gene is the physical juxtaposition of two different genes resulting in a structure consisting of the head of one gene and the tail of the other. Gene fusion is often a primary neoplasia-inducing event in leukemias, lymphomas, solid malignancies as well as benign tumors. Knowledge about fusion genes is crucial not only for our understanding of tumorigenesis, but also for the diagnosis, prognostication, and treatment of cancer. Balanced chromosomal rearrangements, in particular translocations and inversions, are the most frequent genetic events leading to the generation of fusion genes. In the present review, we summarize the existing knowledge on chromosome deletions as a mechanism for fusion gene formation. Such deletions are mostly submicroscopic and, hence, not detected by cytogenetic analyses but by array comparative genome hybridization (aCGH) and/or high throughput sequencing (HTS). They are found across the genome in a variety of neoplasias. As tumors are increasingly analyzed using aCGH and HTS, it is likely that more interstitial deletions giving rise to fusion genes will be found, significantly impacting our understanding and treatment of cancer.
Topics: Cytogenetic Analysis; Gene Fusion; Humans; INDEL Mutation
PubMed: 33893073
DOI: 10.21873/cgp.20251 -
Frontiers in Endocrinology 2023
Topics: Humans; Male; Infertility, Male; Reproduction; Cytogenetic Analysis
PubMed: 37529612
DOI: 10.3389/fendo.2023.1232953 -
Cancer Control : Journal of the Moffitt... Apr 2015New technologies for molecular analysis are increasing our ability to diagnose cancer. (Review)
Review
BACKGROUND
New technologies for molecular analysis are increasing our ability to diagnose cancer.
METHODS
Several molecular analysis technologies are reviewed and their use in the clinical laboratory is discussed.
RESULTS
Select key technologies, including polymerase chain reaction and next-generation sequencing, are helping transform our ability to analyze cancer specimens. As these technological advances become more and more incorporated into routine diagnostic testing, our classification systems are likely to be impacted and our approach to treatment transformed. The routine use of such technology also brings challenges for analysis and reimbursement.
CONCLUSION
These advances in technology will change the way we diagnose, monitor, and treat patients with cancer.
Topics: Cytogenetic Analysis; DNA Mutational Analysis; Humans; Neoplasms; Sequence Analysis
PubMed: 26068758
DOI: 10.1177/107327481502200204 -
Genes Jan 2021The study of vertebrate genome evolution is currently facing a revolution, brought about by next generation sequencing technologies that allow researchers to produce... (Review)
Review
The study of vertebrate genome evolution is currently facing a revolution, brought about by next generation sequencing technologies that allow researchers to produce nearly complete and error-free genome assemblies. Novel approaches however do not always provide a direct link with information on vertebrate genome evolution gained from cytogenetic approaches. It is useful to preserve and link cytogenetic data with novel genomic discoveries. Sequencing of DNA from single isolated chromosomes (ChromSeq) is an elegant approach to determine the chromosome content and assign genome assemblies to chromosomes, thus bridging the gap between cytogenetics and genomics. The aim of this paper is to describe how ChromSeq can support the study of vertebrate genome evolution and how it can help link cytogenetic and genomic data. We show key examples of ChromSeq application in the refinement of vertebrate genome assemblies and in the study of vertebrate chromosome and karyotype evolution. We also provide a general overview of the approach and a concrete example of genome refinement using this method in the species .
Topics: Animals; Chromosomes; Cytogenetic Analysis; Genomics; Sequence Analysis, DNA; Vertebrates
PubMed: 33478118
DOI: 10.3390/genes12010124