المؤلفون: Shu Liu, Nuan Chen, Weihong Zeng, Haimei OuYang, Xunjie Xie, Sisi Wei, Zhiqing Wang, Jinqun Liang, Liying Chen, Jianhui Jiang

المصدر: Cytogenetic and Genome Research. 154:201-208

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Gray matter heterotopia, Microcephaly, Pathology, medicine.medical_specialty, Candidate gene, Developmental Disabilities, Ring chromosome, Biology, 03 medical and health sciences, 0302 clinical medicine, Intellectual Disability, Cytogenetic Abnormality, Intellectual disability, Genetics, medicine, Humans, Ring Chromosomes, Gray Matter, Child, Molecular Biology, Genetics (clinical), 10 year follow up, Infant, Karyotype, Middle Aged, medicine.disease, 030104 developmental biology, Child, Preschool, Face, Chromosomes, Human, Pair 6, Female, 030217 neurology & neurosurgery, Follow-Up Studies

الوصف: Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20db7deed22d6effbfddbc3c04ab040cTest
https://doi.org/10.1159/000488692Test

المؤلفون: E. Engels, Soyhan Bagci, Annette M. Müller, Peter Bartmann, Heiko Reutter, E. Wohlleber, A.L. Berner, Ruthild G. Weber

المصدر: Cytogenetic and Genome Research. 136:308-313

مصطلحات موضوعية: Adult, Male, Infertility, Pediatrics, medicine.medical_specialty, Monosomy, Chromosomes, Human, Pair 20, Trisomy, Chromosomal translocation, Biology, Familial translocation, Translocation, Genetic, Chromosome Painting, Miscarriage, Pregnancy, Genetics, medicine, Humans, Abnormalities, Multiple, Molecular Biology, Genetics (clinical), Partial Trisomy, Infant, Karyotype, medicine.disease, Chromosome Banding, Pedigree, Phenotype, Karyotyping, Chromosomes, Human, Pair 6, Female, Chromosome Deletion

الوصف: Carriers of completely balanced chromosomal translocations have all necessary genetic information. Nevertheless, because of the possibility of maldistribution during gametogenesis, they are at increased risk for infertility, miscarriage, stillbirth or having a child with congenital anomalies including mental retardation. As postnatal clinical reports are infrequent, prediction of clinical course for specific unbalanced karyotypes diagnosed during pregnancy remains difficult. Here, we report the 6th case of partial trisomy 6p and partial monosomy 20p due to an unbalanced adjacent-1 segregation of the rare familial translocation t(6;20)(p21;p13). We give a thorough clinical description of the present case, demonstrating broad phenotypic overlap with the 5 previously published cases reviewed here, providing important data on postnatal outcome.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aeef29149f46e7a69008db432b495f08Test
https://doi.org/10.1159/000337019Test

المؤلفون: Z. Zmitkova, Zdenek Sedlacek, Miroslava Hancarova, Zuzana Zemanova, D Raskova, Y Tan, D Novotna, Alena Puchmajerová, Marketa Vlckova, Jana Drabova, M Trkova

المصدر: Cytogenetic and Genome Research; Vol 136

مصطلحات موضوعية: Male, Marker chromosome, Karyotype, Biology, 03 medical and health sciences, Centromere, Genetics, Humans, Molecular Biology, Gene, Genetic Association Studies, In Situ Hybridization, Fluorescence, Genetics (clinical), 030304 developmental biology, Comparative Genomic Hybridization, 0303 health sciences, 030305 genetics & heredity, Breakpoint, Infant, Chromosome, Phenotype, Molecular biology, Chromosome Banding, Child, Preschool, Chromosomes, Human, Pair 6, Female, Chromosome Deletion, Comparative genomic hybridization

الوصف: Proximal 6q deletions have a milder phenotype than middle and distal 6q deletions. We describe 2 patients with non-overlapping deletions of about 15 and 19 Mb, respectively, which subdivide the proximal 6q region into 2 parts. The aberrations were identified using karyotyping and analysed using mBAND and array CGH. The unaffected mother of the first patient carried a mosaic karyotype with the deletion in all metaphases analysed and a small supernumerary marker formed by the deleted material in about 77% of cells. Her chromosome 6 centromeric signal was split between the deleted chromosome and the marker, suggesting that this deletion arose through the centromere fission mechanism. In this family the location of the proximal breakpoint in the centromere prevented cloning of the deletion junction, but the junction of the more distal deletion in the second patient was cloned and sequenced. This analysis showed that the latter aberration was most likely caused by non-homologous end joining. The second patient also had a remarkably more severe phenotype which could indicate a partial overlap of his deletion with the middle 6q interval. The phenotypes of both patients could be partly correlated with the gene content of their deletions and with phenotypes of other published patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d329035bb6f304cc807d0d03bab965faTest
https://doi.org/10.1159/000334709Test

المؤلفون: S. Selvarajah, Maisa Yoshimoto, Paul S. Thorner, Maria Zielenska, Olga Ludkovski, Paul C. Park, Jane Bayani, Georges Maire, Jeremy A. Squire

المصدر: Cytogenetic and Genome Research. 122:5-15

مصطلحات موضوعية: Male, musculoskeletal diseases, Chromosomes, Artificial, Bacterial, Adolescent, Gene Dosage, High resolution, Bone Neoplasms, Biology, Chromosomal Instability, Chromosome instability, Genetics, medicine, Humans, Child, Interphase, Molecular Biology, In Situ Hybridization, Fluorescence, Genetics (clinical), Oligonucleotide Array Sequence Analysis, Osteosarcoma, Karyotype, Prognosis, medicine.disease, Molecular biology, Karyotyping, Fish , Chromosomes, Human, Pair 6, Female, Virtual karyotype, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 8, Comparative genomic hybridization

الوصف: Osteosarcoma (OS) is characterized by an unstable karyotype which typically has a heterogeneous pattern of complex chromosomal abnormalities. High-resolution array comparative genomic hybridization (CGH) in combination with interphase fluorescence in situ hybridization (FISH) analyses provides a complete description of genomic imbalances together with an evaluation of the contribution of cell-to-cell variation to copy number changes. There have been no analyses to date documenting genomic signatures consistent with chromosomal instability mechanisms in OS tumors using array CGH. In this study, we utilized high-resolution array CGH to identify and characterize recurrent signatures of genomic imbalances using ten OS tumors. Comparison between the genomic profiles identified tumor groups with low, intermediate and high levels of genomic imbalance. Bands 6p22→p21, 8q24 and 17p12→ p11.2 were consistently involved in high copy gain or amplification events. Since these three locations have been consistently associated with OS oncogenesis, FISH probes from each cytoband were used to derive an index of cellular heterogeneity for copy number within each region. OS with the highest degree of genomic imbalance also exhibited the most extreme cell-to-cell copy number variation. Significantly, the three OS with the most imbalance and genomic copy number heterogeneity also had the poorest response to preoperative chemotherapy. This genome wide analysis is the first utilizing oligonucleotide array CGH in combination with FISH analysis to derive genomic signatures of chromosomal instability in OS tumors by studying genomic imbalance and intercellular heterogeneity. This comprehensive genomic screening approach provides important insights concerning the mechanisms responsible for generating complex genomes. The resulting phenotypic diversity can generate tumors with a propensity for an aggressive disease course. A better understanding of the underlying mechanisms leading to OS tumor development could result in the identification of prognostic markers and therapeutic targets.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6f3c4578654ace184b72d1bbf5ce8f4Test
https://doi.org/10.1159/000151310Test

المؤلفون: Jörg Weimer, Walter Jonat, Ute Wiedemann, Norbert Arnold, U.R. Heinrich, M. Cohen

المصدر: Cytogenetic and Genome Research. 114:235-239

مصطلحات موضوعية: media_common.quotation_subject, Mothers, Chromosomal translocation, Allelic Imbalance, Biology, Translocation, Genetic, Genetics, Humans, Molecular Biology, In Situ Hybridization, Fluorescence, Genetics (clinical), Microdissection, media_common, Chromosome Aberrations, Daughter, Chromosomes, Human, Pair 11, Dissection, Chromosome Mapping, Telomere, Phenotype, Molecular biology, Fish , Chromosomes, Human, Pair 6, Female, Dandy-Walker variant

الوصف: We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient’s phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26→qter and a partial trisomy 11q23.3→qter.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89a1677987ff867f710156b1b645671fTest
https://doi.org/10.1159/000094206Test

المؤلفون: Hildegard Kehrer-Sawatzki, H. Röck, W. Krone, A. Siegel, H. Götz

المصدر: Cytogenetic and Genome Research. 86:28-33

مصطلحات موضوعية: Adult, Male, Monosomy, Time Factors, Loss of Heterozygosity, Stimulation, Biology, Fibroblast growth factor, Cell Line, Nondisjunction, Genetic, Dosage Compensation, Genetic, Genetics, medicine, Humans, Selection, Genetic, Child, Fibroblast, Molecular Biology, Alleles, In Situ Hybridization, Fluorescence, Genetics (clinical), Fibroblast growth factor receptor 2, Chromosome Breakage, Fibroblasts, FGF1, medicine.disease, Molecular biology, In vitro, Clone Cells, medicine.anatomical_structure, Receptors, Androgen, Cell culture, Fibroblast Growth Factor 1, Chromosomes, Human, Pair 6, Female, Fibroblast Growth Factor 2, Cell Division, Microsatellite Repeats

الوصف: The appearance of cells with monosomy 6 (mono6 cells) in cultures of human fibroblast-like cells during long-term stimulation with acidic fibroblast growth factor (FGF1) was confirmed in five of the six lines newly investigated. Aneugenic pretreatment at the start of the cultures accelerated the emergence of mono6 cells, as would be expected if selection, rather than induction, is the main mechanism involved. This could be confirmed by using an incidental rearrangement, der(8)t(6p;8p), that emerged in one of the lines by monitoring the proliferation of the mono6 cells (here monosomic for 6p22.1→qter) in mixtures with normal cells. During growth in the presence of FGF1, the proportion of mono6 cells increased six fold, whereas in the absence of FGF1, it declined to background levels. Selection rather than induction of the mono6 cells is further supported by their clonal origin, as ascertained on the basis of X-inactivation patterns in three informative cases. In addition, colonies grown in the presence of FGF1 from single cells did not reveal higher proportions of mono6 cells by fluorescence in situ hybridization analysis than those grown without the growth factor. During permanent stimulation with FGF1, the growth of mono6 cells did not become dependent on FGF1, nor did these cells lose their responsiveness to FGF1. Although evidence in favor of selection of preexistent mono6 cells by FGF1 is provided in this study, the contribution of a primary inducing mechanism cannot be entirely excluded.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f9a65faa17f504c6f10cef79897102e5Test
https://doi.org/10.1159/000015424Test

المؤلفون: Emilio Garcia, Reinhilde Thoelen, M. Aly, Koenraad Devriendt, W.J.M. Van de Ven, Peter M.A. Groenen, J. P. Fryns, Eric F.P.M. Schoenmakers

المصدر: Cytogenetic and Genome Research. 75:210-215

مصطلحات موضوعية: Adult, Chromosome Breakpoints, Chromosome Disorders, Chromosomal translocation, Locus (genetics), Hydronephrosis, Biology, Polymerase Chain Reaction, Oligohydramnios, Translocation, Genetic, Gene mapping, Pregnancy, Chromosome 19, Genetics, medicine, Humans, Kidney Pelvis, Lung, Molecular Biology, In Situ Hybridization, Fluorescence, Genetics (clinical), Chromosome Aberrations, Polycystic Kidney Diseases, medicine.diagnostic_test, Breakpoint, DNA, Fibroblasts, Cosmids, Fetal Diseases, Cosmid, Chromosomes, Human, Pair 6, Female, Ureter, Chromosomes, Human, Pair 19, Ureteral Obstruction, Fluorescence in situ hybridization

الوصف: Hydronephrosis caused by pelvi-ureteric junction obstruction (PUJO) is a frequent urological malformation assumed to result from a deficient development of the ureteric bud. The exact etiology of pelvi-ureteric junction stenosis is unknown, but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. We encountered a patient with a de novo autosomal t(6;19)(p21;q13.1) and attendant bilateral multicystic renal dysplasia (MRD), bilateral PUJO resulting in massive hydronephrosis, and an associated von Mayer-Rokitansky-Küster disorder. On the basis of the presumption that in this patient the putative hydronephrosis gene might be disrupted by the translocation, we sought to isolate DNA from the breakpoint regions as the initial step in a strategy to identify genes affected by the t(6;19). Using sequential rounds of fiuorescence in situ hybridization (FISH) with cosmids selected from a detailed integrated map of the long arm of chromosome 19, we have identified a cosmid clone that spans the breakpoint. The position of the breakpoint was further localized by Southern blot analysis. Using a vectorette PCR approach, rearranged DNA fragments were isolated and, by comparative nucleotide sequence analysis, these were shown to contain ectopic sequences. A cosmid clone containing these ectopic sequences was isolated and shown by CASH (chromosome assignment using somatic cell hybrids) and FISH (fluorescence in situ hybridization) analysis to map to the short arm of chromosome 6 and to span the breakpoint found in the MRD patient. The isolated cosmid clones are useful reagents for analysis of other MRD patients and for the search for genes at or flanking the breakpoints.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::718d0c0a91b4361c7412109efa277a29Test
https://doi.org/10.1159/000134485Test

المؤلفون: Marine Guillaud-Bataille, R. Berger, Alain Bernheim, H. Waxin, S. Toujani, C. Richon, P. Dessen

المصدر: Cytogenetic and genome research. 119(3-4)

مصطلحات موضوعية: Genetics, Daughter, media_common.quotation_subject, Breakpoint, Gene Dosage, Chromosome Breakage, DNA, Biology, Familial translocation, Translocation, Genetic, Cell Line, Array-Based Comparative Genomic Hybridization, Chromosomes, Human, Pair 2, Karyotyping, Humans, Chromosomes, Human, Pair 6, Female, DNA Probes, Molecular Biology, Genetics (clinical), In Situ Hybridization, Fluorescence, media_common, Oligonucleotide Array Sequence Analysis

الوصف: A 244K genome-wide array based comparative genomic hybridization study was carried out in a familial translocation t(2;6)(p25;p21) balanced in the mother and unbalanced in her daughter. In the past, this translocation has allowed us to localize the HLA multigene cluster to chromosome 6. With microarray technology, confirmation of the chromosome localization of the HLA system was easily obtained, showing that such approach may be applied to the breakpoint localizations of other familial structural changes when they are unbalanced. The disruption of genes at the translocation breakpoints that did not have any phenotypic consequences in the parent will allow the generation of a map of ‘haplotolerant genes’. In addition, many genomic variants were detected with this technology, enlarging the possibility of analyzing their possible contribution to phenotypic diversity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efa3f98b3855412963781aefa7569486Test
https://pubmed.ncbi.nlm.nih.gov/18253027Test

المؤلفون: Michael B. Petersen, Yolanda Gyftodimou, Maria Grigoriadou, Haris Kokotas, Efi Pandelia, Catherine Sarri, Kristin Mrasek, S. Kalogirou, Anja Weise

المصدر: Cytogenetic and genome research. 114(3-4)

مصطلحات موضوعية: Genetic Markers, Heart Defects, Congenital, Marker chromosome, Biology, Craniofacial Abnormalities, Gene duplication, Genetics, medicine, Humans, Supernumerary, Abnormalities, Multiple, Child, Molecular Biology, Small supernumerary marker chromosome, Genetics (clinical), In Situ Hybridization, Fluorescence, Chromosome Aberrations, medicine.diagnostic_test, Chromosome, Chromosome Mapping, Karyotype, medicine.disease, Uniparental disomy, Karyotyping, Chromosomes, Human, Pair 6, Female, Fluorescence in situ hybridization

الوصف: We describe a female patient with a small supernumerary marker chromosome (sSMC) present in mosaic and characterized in detail by fluorescence in situ hybridization (FISH) using all 24 human whole chromosome painting probes, multicolor banding (MCB) and subcentromere specific multicolor FISH (subcenM-FISH). The sSMC was demonstrated to be derived from chromosome 5 and the karyotype of our patient was as follows: 47,XX,+mar.ish r(5)(::p13.2∼p13.3→q11.2::) [60%]/46,XX [40%]. Partial trisomy for the proximal 5p and q chromosomal regions is a rare event. A critical region exists at 5p13 for the phenotype associated with duplication 5p. As far as we know, eight similar cases have been published up to now. We describe a new case which, to our knowledge, is the first characterized in such detail. The role of uniparental disomy (UPD) in cases of SMC is also discussed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51e39ae587158cdee29a0f332f5219dbTest
https://pubmed.ncbi.nlm.nih.gov/16954675Test

المؤلفون: T H, Vu, R L, Jirtle, A R, Hoffman

المصدر: Cytogenetic and genome research. 113(1-4)

مصطلحات موضوعية: Male, Exons, DNA Methylation, Receptor, IGF Type 2, Evolution, Molecular, Genomic Imprinting, Mice, Gene Expression Regulation, Species Specificity, Vertebrates, Animals, Humans, Chromosomes, Human, Pair 6, Female

الوصف: The epigenetic marks on the IGF2R gene that encodes a receptor responsible for IGF-II degradation consist of differentially methylated DNA in association with multiple modifications on the associated histones. We review these epigenetic marks across various species during the evolution of IGF2R imprinting. Both IGF2 and IGF2R genesare imprinted in the mammal lineage that diverged from Monotremata approximately 150 million years ago. While IGF2 is consistently imprinted in all mammals following its divergence, IGF2R imprinting disappears in the Euarchonta lineage, including human species, approximately 75 million years ago. Differential DNA methylation marks on the two parental alleles correlate with imprinting in all imprinted genes including IGF2R. While the DNA methylation marks in the IGF2R promoter region 1 (DMR1) correlate with IGF2R allelic expression, the DNA methylation marks in the intron region 2 (DMR2) fail to correlate with IGF2R imprinting status in a number of species. Human IGF2R and mouse neuronal Igf2r are not imprinted despite the presence of DMR2. We have noted that human IGF2R is not imprinted in more than 100 informative samples including various tumor tissues. Furthermore, opossum (Marsupialia) IGF2R is consistently imprinted despite the absence of DMR2. These lines of evidence indicate that DNA methylation marks in DMR2 are neither necessary nor sufficient for consistent imprinting of IGF2R across species. Histone modification marks, however, correlate more consistently with the tissue-specific and species-specific imprinting status of IGF2R in human and mouse. Acetylated histone H3 and H4 and methylated lysine 4 of H3 (H3-K4Me) associate with transcriptionally active alleles while tri-methylated lysine 9 of H3 (H3-K9Me3) marks the silenced alleles. In the mouse, an antisense non-coding transcript called Air is transcribed from DMR2 on the paternal allele, and this imprinted transcript plays a central role in Igf2r imprinting. Mouse Igf2r imprinting depends on an Air RNA while the existence of AIR in other species is unknown. Overall, DNA methylation, histone acetylation, and histone methylation play a vital role in coordinating IGF2R allelic expression across all species. Rare monoallelic or skewed allelic expression of human IGF2R and their biological importance warrants further rigorous study.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::7bb911973168312dca618124213bb865Test
https://pubmed.ncbi.nlm.nih.gov/16575181Test