• MeSH
• aneuploidie MeSH
• chromozomální poruchy genetika   metabolismus   psychologie   MeSH
• modely nemocí na zvířatech MeSH
• mozek metabolismus   MeSH
• myši MeSH
• trizomie MeSH
• umělé bakteriální chromozomy genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

RESEARCH QUESTION: What is the incidence and origin of meiotic whole and segmental aneuploidies detected by karyomapping at a blastocyst stage in human-derived IVF embryos? What is the distribution of various types of errors, including rare chromosomal abnormalities? DESIGN: The incidence of chromosomal aneuploidies was assessed in 967 trophectoderm biopsies from 180 couples who underwent 215 cycles of IVF with preimplantation genetic testing for monogenetic disease with a known causal mutation with a mean maternal age of 32.7 years. DNA from both parents and a reference sample was genotyped together with the analysed trophectoderm samples by karyomapping (single-nucleotide-polymorphism-based array). RESULTS: Chromosomal abnormalities were detected in 31% of the analysed samples. At least one whole chromosomal aneuploidy was detected in 27.1% of the trophectoderm biopsies, whereas a segmental aneuploidy was detected in 5.1% of the trophectoderm biopsies. Our results reveal that segmental aneuploidies predominantly affect paternally derived chromosomes (70.4%; P < 0.01) compared with whole chromosomal aneuploidies that more frequently affect maternally derived chromosomes (90.1%; P < 0.0001). Also, the frequency of meiosis I (MI) and meiosis II (MII) errors was established in meiotic trisomies; MI errors were observed to be more frequent (n = 102/147 [69.4%]) than MII errors (n = 45/147 [30.6%]). CONCLUSIONS: Karyomapping is a robust method that is suitable for preimplantation genetic testing for monogenetic disease and for detecting meiotic aneuploidies, including meiotic segmental aneuploidies, and provides complex information about their parental origin. Our results revealed that segmental aneuploidy more frequently affects paternal chromosomes compared with whole chromosomal aneuploidy in human IVF embryos at the blastocyst stage.

• MeSH
• aneuploidie * MeSH
• chromozomální aberace * MeSH
• chromozomální poruchy epidemiologie   MeSH
• dospělí MeSH
• fertilizace in vitro * MeSH
• genetické testování MeSH
• incidence MeSH
• karyotypizace MeSH
• lidé MeSH
• meióza * MeSH
• preimplantační diagnóza metody   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The single-celled parasite Giardia intestinalis (Diplomonadida) has two equally sized nuclei in one cell. The nuclei have been considered identical. We have previously shown that they contain different chromosomal sets and proceed through the cell cycle with some asynchrony. Here, we demonstrate by fluorescence in situ hybridization that several genes from chromosome 5 are lost in one of the two nuclei of the WBc6 Giardia line. The missing segment stretches over at least 50kb near the 5' chromosome end. In both WB and WBc6 Giardia cell lines, chromosome 5 is trisomic in one nucleus and monosomic in the other nucleus. The described chromosomal deletion has always been observed at the monosomic chromosome in WBc6; however, the deletion was not detected in the parent line WB. The chromosomal segment was thus initially lost after biological cloning of WB, which gave rise to clone WBc6. We show that Giardia is capable of carrying out gene expression from only one nucleus. The two nuclei display a certain level of diversity, making each of them irreplaceable. The doubled karyomastigonts of diplomonads likely have separate functions both in the mastigont/flagellar organization and in chromosomal and gene content. To our knowledge, our results offer the first methodical approach to differentiating the two, so far indistinguishable nuclei. Copyright © 2019 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

• MeSH
• buněčné jádro genetika   MeSH
• časové faktory MeSH
• chromozomální delece MeSH
• delece genu MeSH
• Giardia lamblia * genetika   ultrastruktura   MeSH
• hybridizace in situ fluorescenční normy   MeSH
• komplementární DNA MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• mitóza MeSH
• monozomie * MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese fyziologie   MeSH
• reverzní transkripce MeSH
• RNA protozoální genetika   izolace a purifikace   MeSH
• signální transdukce MeSH
• trizomie genetika   MeSH

Autosomal trisomies and monosomies bring serious threats to embryonic development through transcriptional disarray caused primarily by the dosage effect of the aneuploid part of the genome. The present study compared the effect of a mouse-viable 30-Mb segmental trisomy on the genome-wide transcriptional profile of somatic (liver) cells and male germ cells. Although the 1.6-fold change in expression of triplicated genes reflected the gene dosage in liver cells, the extra copy genes were compensated in early pachytene spermatocytes, showing 1.18-fold increase. Although more pronounced, the dosage compensation of trisomic genes was concordant with the incidence of HORMAD2 protein and histone gammaH2AX markers of unsynapsed chromatin. A possible explanation for this includes insufficient sensitivity to detect the meiotic silencing of unsynapsed chromatin markers in the 30-Mb region of the chromosome or an earlier silencing effect of another epigenetic factor. Taken together, our results indicate that the meiotic silencing of unsynapsed chromatin is the major, but most likely not the only, factor driving the dosage compensation of triplicated genes in primary spermatocytes.

• MeSH
• aneuploidie MeSH
• chromatin genetika   MeSH
• fenotyp MeSH
• genom * MeSH
• játra fyziologie   MeSH
• kompenzace dávky (genetika) * MeSH
• meióza genetika   MeSH
• mužská infertilita genetika   MeSH
• myši inbrední C57BL MeSH
• spermatocyty fyziologie   MeSH
• synaptonemální komplex genetika   MeSH
• těhotenství MeSH
• tělesná hmotnost genetika   MeSH
• transkriptom MeSH
• translokace genetická genetika   MeSH
• trizomie genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Gene amplification is a frequent genetic abnormality in solid tumors, and many oncogenes are activated in this way. In acute myeloid leukemia (AML), a frequent target of gene amplification is chromosome 11, particularly chromosome region 11q23, including the MLL (myeloid/lymphoid leukemia) gene. However, the number of other amplicons from the long arm of chromosome 11 has also been described. Duplication/amplification of chromosome 11 was found by cytogenetic methods in 10 of 119 newly diagnosed patients with AML. The amplification was presented as: amplification including only the 5' segment of the MLL gene (1 patient), trisomy 11 (3 patients), partial trisomy 11q (2 patients), isochromosome 11q (1 patient), and multiple amplification of specific regions (3 patients). In two cases, amplification involved parts of not only long arm but also of short arm of the chromosome 11: 11p15 and 11p11.1 to 11p13.

• MeSH
• akutní myeloidní leukemie diagnóza   genetika   MeSH
• amplifikace genu MeSH
• dospělí MeSH
• duplikace genu MeSH
• hybridizace in situ fluorescenční MeSH
• karyotypizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• prognóza MeSH
• senioři MeSH
• trizomie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chromosomal translocations are acquired genetic rearrangements in human cancers. Jumping translocations are rare nonreciprocal rearrangements involving the same donor chromosome segment translocated to two or more recipient chromosomes. In this report, we describe a patient with Burkitt lymphoma/leukemia (BL) and a complex karyotype including a t(2;8)(p12;q24), copy-neutral loss of heterozygosity at 17p13.1-p13.3 and 19q13.1-q13.2, trisomy 20, and two uncommon chromosomal aberrations. The first uncommon aberration was a complex rearrangement of chromosome 15 (probably the consequence of chromothripsis) masked by an apparently balanced reciprocal translocation, t(11;15)(p11.2;q21). The second one was a special type of unbalanced "vice versa" jumping translocation, which involved the same acceptor chromosome arm (13q) and various donor chromosome segments. It is unclear whether both atypical rearrangements are the consequence of the TP53 alteration or whether assumed chromothripsis influenced the development of the jumping-like translocation. However, the presence of the t(11;15)(p11.2;q21) in all pathological cells suggests that it occurred in the early stage of the disease, whereas the jumping-like translocation, as an additional change, subsequently accelerated the progression of the disease.

• MeSH
• Burkittův lymfom diagnóza   genetika   MeSH
• chromozomální delece MeSH
• chromozomální poruchy genetika   MeSH
• dospělí MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 13 genetika   MeSH
• lidské chromozomy, pár 15 genetika   MeSH
• lidské chromozomy, pár 20 genetika   MeSH
• mozaicismus MeSH
• nádorový supresorový protein p53 genetika   MeSH
• translokace genetická * MeSH
• trizomie genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Interphase fluorescence in situ hybridization was used to detect common deletions in B-CLL patients as well as trisomy 12 and aberrations of IgH gene complex at 14q32.33 where we evaluated not only translocation-like signal pattern but also deletions. 120 (82%) patients showed genetic changes - del(13)(q14) 95 (62%), deletion of ATM gene 22 (15%), deletion of p53 gene 25 (17%) and trisomy 12 was proved in 18 (12%) cases. IgH rearrangements were detected in 45 (31%), split of the signals in 11 (8%), deletion of 3' segment flanking IgH gene in 5 (3%) and deletions of variable segment in 29 (20%) patients. Although deletions of 3' segment flanking IgH gene complex are supposed to have an adverse prognostic impact and the genetic background of variable segment deletions is believed to be most probably physiological, we assumed a detailed mapping of the 14q32.33 region will be needed to unravel these mysteries.

• MeSH
• analýza přežití MeSH
• chromozomální aberace MeSH
• chronická lymfatická leukemie genetika   MeSH
• cytogenetické vyšetření MeSH
• diagnostické techniky molekulární MeSH
• financování organizované MeSH
• hybridizace in situ fluorescenční MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 12 MeSH
• lidské chromozomy, pár 13 MeSH
• lidské chromozomy, pár 14 MeSH
• mutace MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• trizomie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

Preimplantační genetická diagnostika představuje soubor genetických nebo cytogenetických vyšetření, pomocí kterých můžeme odhalit genetické abnormality embrya před jeho přenosem do dělohy matky. I v této oblasti se začínají využívat moderní genomické technologie založené na DNA mikročipech. Cílem práce je informovat o možnostech i prvních zkušenostech s celogenomovým vyšetřením chromozomových abnormalit v buňkách trofoektodermu pětidenních embryí pomocí techniky single cell array-CGH (komparativní genomová hybridizace na mikročipech) s využitím 60-merové oligonukleotidové platformy DNA mikročipů CytoSure 8 × 15 K Aneuploidy Array. I když byla tato platforma původně vyvinuta pro genetická vyšetření prováděná na neamplifikované DNA, současné pokroky v oblasti genomiky jedné buňky umožnily využít tuto technologii v oblasti preimplantačních genetických analýz. Metoda single cell array-CGH byla validována testováním 30 negativních a pozitivních kontrol, tj. amplifikací a následným vyšetřením DNA izolované z 5–10 buněk s normálním karyotypem a ze vzorků buněk se známými početními i strukturními abnormalitami chromozomů. Následně jsme úspěšně amplifikovali a vyšetřili vzorky 118 embryí a detekovali aneuploidie u 26,7 % a segmentální nebalancované změny u 6,8 % embryí. Naše zkušenosti potvrzují, že oligonukleotidové platformy DNA mikročipů s vysokým rozlišením jsou vhodné jak pro preimplantační genetický screening aneuploidií všech 23 párů chromozomů embrya, tak pro citlivou preimplantační diagnostiku segmentálních nebalancovaných aberací typu delecí, duplikací či amplifikací.

Preimplantation genetic diagnosis (PGD) is a complex approach for detecting genetic abnormalities in early-stage embryos using genetic or molecular cytogenetic methods. Recently, single cell genomic methods based on DNA microarrays have been used for PGD. In the presented paper, we discuss and demonstrate the possibility to detect copy number variation (CNVs) in trophectoderm cells biopsied from 5-day embryos using 60-mer oligonucleotide-based array-CGH with CytoSure 8 × 15K Aneuploidy Array. Whereas this microarray platform was originally designed for analysis of unamplified DNA derived from many cells, the new methods, developed for single-cell genomics, allow the application of oligo arrays technology in preimplanation genetic diagnosis. Preclinical validation of single cell array-CGH was made by analysis of 30 positive and negative controls. Validation process included whole genome amplification of DNA from 5–10 cells with normal karyotype and from samples with known aneuploidies and structural aberrations. Subsequently, we analyzed the whole genome profiles in 118 embryos; aneuploidies of chromosomes were observed in 26.7%; segmental imbalances were proved in 6.8% of embryos. Our first experience confirmed that this oligonucleotide-based array technique enables high-resolution preimplantation aneuploidy screening of all the 23 chromosome pairs and sensitive preimplantation diagnosis of segmental imbalances such as deletions, duplications and amplifications.

• MeSH
• asistovaná reprodukce MeSH
• chromozomální aberace MeSH
• DNA analýza   MeSH
• embryo savčí MeSH
• embryonální vývoj MeSH
• fertilizace in vitro MeSH
• genetická predispozice k nemoci embryologie   prevence a kontrola   MeSH
• genetické testování * metody   přístrojové vybavení   trendy   MeSH
• implantace embrya genetika   MeSH
• lidé MeSH
• molekulární biologie trendy   MeSH
• preimplantační diagnóza * metody   trendy   MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů * MeSH
• srovnávací genomová hybridizace trendy   MeSH
• trizomie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

The single-celled parasite Giardia intestinalis (Diplomonadida) has two equally sized nuclei in one cell. The nuclei have been considered identical. We have previously shown that they contain different chromosomal sets and proceed through the cell cycle with some asynchrony. Here, we demonstrate by fluorescence in situ hybridization that several genes from chromosome 5 are lost in one of the two nuclei of the WBc6 Giardia line. The missing segment stretches over at least 50 kb near the 5' chromosome end. In both WB and WBc6 Giardia cell lines, chromosome 5 is trisomic in one nucleus and monosomic in the other nucleus. The described chromosomal deletion has always been observed at the monosomic chromosome in WBc6; however, the deletion was not detected in the parent line WB. The chromosomal segment was thus initially lost after biological cloning of WB, which gave rise to clone WBc6. We show that Giardia is capable of carrying out gene expression from only one nucleus. The two nuclei display a certain level of diversity, making each of them irreplaceable. The doubled karyomastigonts of diplomonads likely have separate functions both in the mastigont/flagellar organization and in chromosomal and gene content. To our knowledge, our results offer the first methodical approach to differentiating the two, so far indistinguishable nuclei.

• MeSH
• buněčné jádro genetika   MeSH
• časové faktory MeSH
• chromozomální delece MeSH
• delece genu MeSH
• Giardia lamblia genetika   ultrastruktura   MeSH
• hybridizace in situ fluorescenční normy   MeSH
• komplementární DNA genetika   MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• mitóza MeSH
• monozomie * genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese fyziologie   MeSH
• reverzní transkripce MeSH
• RNA protozoální genetika   izolace a purifikace   MeSH
• signální transdukce MeSH
• trizomie * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Abnormalities of chromosome 1 are among the most frequent chromosomal aberrations in patients with multiple myeloma (MM) and are considered a poor-risk genetic feature. To define the frequency and minimal region of 1q gain, we performed immunophenotyping and fluorescence in situ hybridization, comparative genomic hybridization (CGH), and array-CGH in 30 patients in relapse and progression of MM. Gain of 1q21 was found in 15 patients (50%), and in 14 of them whole-arm gain was found. One of these 14 patients had trisomy of chromosome 1 together with whole arm 1q gain, and two others had segmental duplication together with whole arm 1q gain. Segmental duplication of 1q21.1 approximately q23.1 alone was found in one patient. These results confirmed a high frequency of 1q aberrations and revealed that the vast majority of patients with 1q aberration in relapse and progression of MM display whole arm 1q gain. Finally, we observed that 1q gain is highly associated with number of additional changes.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 1 genetika   MeSH
• mnohočetný myelom genetika   patologie   MeSH
• progrese nemoci MeSH
• recidiva MeSH
• senioři MeSH
• srovnávací genomová hybridizace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH