Showing papers on "Karyotype published in 2002"
TL;DR: In this paper, field-collected specimens of all known taxa in the Anopheles gambiae complex were analyzed on the basis of chromosome inversions with reference to a standard polytene chromosome map.
Abstract: Field-collected specimens of all known taxa in the Anopheles gambiae complex were analyzed on the basis of chromosome inversions with reference to a standard polytene chromosome map. The phylogenetic relationships among the seven described species in the complex could be inferred from the distribution of fixed inversions. Nonrandom patterns of inversion distribution were observed and, particularly on chromosome arm 2R, provided evidence for genetically distinct populations in A. gambiae, A. arabiensis, and A. melas. In A. gambiae from Mali, stable genetic differentiation was observed even in populations living in the same region, suggesting a process of incipient speciation which is being confirmed by studies with molecular markers. The possible role of chromosome differentiation in speciation of the A. gambiae complex and in the emergence of distinct chromosomal forms within the nominal species is discussed in relation to human malaria.
460 citations
TL;DR: Extensive cytogenetic analyses on a population of the leptodactylid frog Eleutherodactylus riveroi in northern Venezuela revealed the existence of multiple XXAA♂/XYAA♀/XAAY as discussed by the authors.
Abstract: Extensive cytogenetic analyses on a population of the leptodactylid frog Eleutherodactylus riveroi in northern Venezuela revealed the existence of multiple XXAA♂/XYAA♀/XAAY
213 citations
TL;DR: Sandal et al. as mentioned in this paper performed an extensive characterization of the chromosome complement of the species and found that these chromosome rearrangements are early events in speciation of this group.
Abstract: Lotus japonicus is a model plant for the legume family. To facilitate map-based cloning approaches and genome analysis, we performed an extensive characterization of the chromosome complement of the species. A detailed karyotype of L. japonicus Gifu was built and plasmid and BAC clones, corresponding to genetically mapped markers (see the accompanying article by Sandal et al. 2002, this issue), were used for FISH to correlate genetic and chromosomal maps. Hybridization of DNA clones from 32 different genomic regions enabled the assignment of linkage groups to chromosomes, the comparison between genetic and physical distances throughout the genome, and the partial characterization of different repetitive sequences, including telomeric and centromeric repeats. Additional analysis of L. filicaulis and its F 1 hybrid with L. japonicus demonstrated the occurrence of inversions between these closely related species, suggesting that these chromosome rearrangements are early events in speciation of this group.
191 citations
TL;DR: Significant differences in the relative expression levels between chromosomes were detected suggesting that genomic control mechanisms may act over larger distances than previously thought and support a model of a subtle primary upregulation of genes on the trisomic chromosome resulting in a secondary, generalized and more extreme transcriptional misregulation.
Abstract: We present transcriptome analyses of primary cultures of human fetal cells from pregnancies affected with trisomy 21 (t21) and trisomy 13 (t13). Pooled mRNA samples from t21 and t13 cases were used for comparative hybridizations to cDNA arrays with pooled mRNA from normal cells. When the array cDNAs were grouped by chromosomal location the relevant trisomic chromosome could be clearly identified as showing the most significant misregulation. The average level of transcription on the trisomic chromosome was increased only approximately 1.1-fold compared to normal cells on array analysis. Since the karyotype could be accurately predicted by the transcriptome this could provide a novel method of detecting aneusomy of unknown position. Subsequent analysis of individuals cases demonstrated that variation in transcriptional profiles between samples within each class made transcriptional karyotyping difficult without pooling or the use of arrays with a higher proportion of all human cDNAs. Interestingly, consistent differences in the relative expression levels between chromosomes were detected suggesting that genomic control mechanisms may act over larger distances than previously thought. Most (>95%) >+/-2 SD misregulated genes did not map to the trisomic chromosome and significant misregulation was more common in t13 than t21. These data support a model of a subtle primary upregulation of genes on the trisomic chromosome resulting in a secondary, generalized and more extreme transcriptional misregulation. It seems likely that the degree of this misregulation determines the severity of the phenotype in most aneuploidy.
174 citations
TL;DR: In contrast to LPL tumors that are not associated with paraproteinemia and that have frequent t(9;14)(p13;q32) translocations, IgH translocations are not found in Waldenström macroglobulinemia, a form of LPL tumor distinguished by IgM paraproteemia.
172 citations
TL;DR: Despite the tremendous shuffling of chromosomes during the course of mammalian evolution, the pattern of genomic imbalances is conserved between BRCA1-associated mammary gland tumors in mice and humans.
Abstract: BRCA1 mutation carriers have an increased susceptibility to breast and ovarian cancer. Excision of exon 11 of Brca1 in the mouse, using a conditional knockout (Cre-loxP) approach, results in mammary tumor formation after long latency. To characterize the genomic instability observed in these tumors, to establish a comparative map of chromosomal imbalances and to contribute to the validation of this mouse model of breast cancer, we have characterized chromosomal imbalances and aberrations using comparative genomic hybridization (CGH), and spectral karyotyping (SKY). We found that all tumors exhibit chromosome instability as evidenced by structural chromosomal aberrations and aneuploidy, yet they display a pattern of chromosomal gain and loss that is similar to the pattern in human breast carcinomas. Of note, nine of 15 tumors exhibited a gain of distal chromosome 11, a region that is orthologous to human chromosome 17q11-qter, the mapping position of Erbb2. However, our analysis suggests that genes distal to Erbb2 are the main targets of amplification. Four of the tumors also exhibited a copy number loss of proximal chromosome 11 (11A-B), a region orthologous to human 17p. In eight of the tumors we observed whole or partial gain of chromosome 15 centering on 15D2-D3 (orthologous to human chromosome 8q24), the map location of the c-Myc gene, and six of the tumors exhibited copy number loss of whole or partial chromosome 14, including 14D3, the map location of Rb1. We conclude that despite the tremendous shuffling of chromosomes during the course of mammalian evolution, the pattern of genomic imbalances is conserved between BRCA1-associated mammary gland tumors in mice and humans. Western blot analysis showed that while p53 is absent or mutated in some tumors, at least two tumors revealed wild-type protein, suggesting that other genetic events may lead to tumorigenesis. Similar to BRCA1-deficient mouse embryonic fibroblasts, the tumor cells contained supernumerary functional centrosomes with intact centrioles whose presence results in multipolar mitoses and aneuploidy.
153 citations
TL;DR: The level of minimal residual disease following induction therapy can be a reliable predictor of outcome in ALL and the classification of patients into prognostic groups based on cytogenetics is not always as predicted.
Abstract: An important factor in the diagnosis of acute lymphoblastic leukemia (ALL) is that karyotype is an independent prognostic indicator, with an impact on the choice of treatment. Outcome is related to the number of chromosomes. For example, high hyperdiploidy (51–65 chromosomes) is associated with a good prognosis, whereas patients with near haploidy (23–29 chromosomes) have a poor outcome. The discovery of recurring chromosomal abnormalities in the leukemic blasts of patients with ALL has identified a large number of genes involved in leukemogenesis. Certain specific genetic changes are related to prognosis. The ETV6/AML1 fusion arising from the translocation (t12;21) (p13;q22) has been associated with a good outcome; the BCR/ABL fusion of (t9;22)(q34;q11), rearrangements of the MLL gene, and abnormalities of the short arm of chromosomes 9 involving the tumor suppressor genes p16INK4A have a poor prognosis. Unfortunately, the classification of patients into prognostic groups based on cytogenetics is not always as predicted. Even when other clinically based risk factors are taken into account, some patients with good-risk cytogenetic features will relapse. In the search for new measures of prognosis, it has recently emerged that the level of minimal residual disease following induction therapy can be a reliable predictor of outcome in ALL.
151 citations
TL;DR: This data indicates that genome‐wide surveys for chromosome aberrations in primary cutaneous T‐cell lymphoma (CTCL) are limited and further research is needed to assess the importance of these surveys for informing treatment decisions.
Abstract: Summary
Background Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited.
Objectives To investigate genetic aberrations in CTCL.
Methods We analysed 18 cases of Sezary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies.
Results CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean ± SD number of CIs per sample was 1·8 ± 2·4, with losses (1·2 ± 2·0) slightly more frequent than gains (0·6 ± 1·0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25).
Conclusions These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies.
146 citations
TL;DR: The studies also implicate the products of the p53 and XPD genes in the regulation of the fidelity of chromosome segregation at mitosis, and Quantitative relationships between the two major causes of aneuploidy, chromosome loss and non-disjunction, can be determined.
Abstract: A comprehensive evaluation of the genotoxic potential of chemicals requires the assessment of the ability to induce gene mutations and structural chromosome (clastogenic activity) and numerical chromosome (aneugenic activity) aberrations. Aneuploidy is a major cause of human reproductive failure and an important contributor to cancer and it is therefore important that any increase in its frequency due to chemical exposures should be recognized and controlled. The in vitro binucleate cell micronucleus assay provides a powerful tool to determine the ability of a chemical to induce chromosome damage. The application of an anti-kinetochore antibody to micronuclei allows their classification into kinetochore-positive and kinetochore-negative, indicating their origin by aneugenic or clastogenic mechanisms, respectively. The availability of chromosome-specific centromere probes allows the analysis of the segregation of chromosomes into the daughter nuclei of binucleate cells to evaluate chromosome non-disjunction. Quantitative relationships between the two major causes of aneuploidy, chromosome loss and non-disjunction, can be determined. The mechanisms leading to chromosome loss and non-disjunction can be investigated by the analysis of morphological and structural changes in the cell division apparatus by the application of specific stains and antibodies for various cell division components. We illustrate such analyses by the demonstration of the interaction of the monomer bisphenol-A with the centrosome of the mitotic spindle and the folic acid antagonist pyrimethamine with the centromeres of chromosomes. Both types of modifications lead to the induction of aneuploidy in exposed cells. Our studies also implicate the products of the p53 and XPD genes in the regulation of the fidelity of chromosome segregation at mitosis.
139 citations
TL;DR: The results suggest that the degree of chromosomal differentiation among the four Pinus species is very low and that the proximal regions vary in their DNA sequences.
Abstract: Chromosomal landmarks in four Pinus species: P. densiflora, P. thunbergii, P. sylvestris, and P. nigra were identified by fluorescence in situ hybridization (FISH) using hapten- or fluorochrome-labeled probes for the plant telomere repeat, centromeric repeat (PCSR), and rDNA. FISH landmarks were located at the interstitial and proximal regions of chromosomes and allowed us to identify nearly all of the homologous chromosomes in each species. A comparative analysis of the FISH karyotypes among the four species showed that the interstitial FISH signals obtained by hybridization with the telomere and rDNA sequences were stable and could be used to identify homologous chromosomes among species. The identification of homologous chromosomes among species facilitated a detailed comparative karyotype analysis. The results suggest that the degree of chromosomal differentiation among the four Pinus species is very low and that the proximal regions vary in their DNA sequences. The similarities and differences among FISH karyotypes are discussed in relation to phylogeny.
126 citations
TL;DR: Both whole chromosome non-disjunction and chromatid predivision contributed to the formation of aneuploid oocytes, but the numerical abnormalities due to single chromatids significantly exceeded conventionalnon-disjunctions.
Abstract: BACKGROUND: Although numerous studies have been published on the chromosomal constitution of in-vitro unfertilized human oocytes, data remain highly variable and controversial because of the size of oocyte samples, technical reservations and potential misinterpretation. METHODS: A cytogenetic study was undertaken on 3042 unfertilized human oocytes recovered from 792 women participating in an IVF programme for various infertility problems. Both a gradual fixation technique and an R-banding procedure were used. RESULTS: The analysis was successful in 1397 oocytes (45.9%) for which interpretable metaphases were obtained. Of the 1397 oocyte karyotypes, 1088 (77.9%) were normal (23,X). The overall frequency of chromosomal abnormality was 22.1%. No correlation was found between the rate of abnormalities and the type of infertility. Aneuploidy was observed in 151 cells (10.8%), consisting of 5.4% hypohaploidies, 4.1% hyperhaploidies, 0.8% complex aneuploidies and 0.05% extreme aneuploidies with less than 18 chromosomes. Both whole chromosome non-disjunction and chromatid predivision contributed to the formation of aneuploid oocytes, but the numerical abnormalities due to single chromatids significantly exceeded conventional non-disjunctions. Abnormalities also included 5.4% diploid oocytes, 3.8% sets of chromatids alone and 2.1% structural aberrations. Aneuploidy was found in all chromosome groups. However, groups E and G exhibited significantly higher frequencies of non-disjunction than expected, whereas groups A and B showed a significantly low incidence of aneuploidy. CONCLUSIONS: The implication of both chromosome and chromatid abnormalities in the occurrence of non-disjunction are discussed in relation to the recent data on chromatid cohesion throughout cell division. The results were consistent with the hypothesis of an unequal occurrence of non-disjunction among the chromosome groups in female meiosis.
TL;DR: Although originally considered recalcitrant, wheat seems to be suitable for the development of flow cytogenetics and the technology can be applied to the physical mapping of DNA sequences, the targeted isolation of molecular makers and the construction of chromosome- and arm-specific DNA libraries.
Abstract: Previously, we reported on the development of procedures for chromosome analysis and sorting using flow cytometry (flow cytogenetics) in bread wheat. That study indicated the possibility of sorting large quantities of intact chromosomes, and their suitability for analysis at the molecular level. However, due to the lack of sufficient differences in size between individual chromosomes, only chromosome 3B could be sorted into a high-purity fraction. The present study aimed to identify wheat stocks that could be used to sort other chromosomes. An analysis of 58 varieties and landraces demonstrated a remarkable reproducibility and sensitivity of flow cytometry for the detection of numerical and structural chromosome changes. Changes in flow karyotype, diagnostic for the presence of the 1BL·1RS translocation, have been found and lines from which translocation chromosomes 5BL·7BL and 4AL·4AS-5BL could be sorted have been identified. Furthermore, wheat lines have been identified which can be used for sorting chromosomes 4B, 4D, 5D and 6D. The ability to sort any single arm of the hexaploid wheat karyotype, either in the form of a ditelosome or a isochromosome, has also been demonstrated. Thus, although originally considered recalcitrant, wheat seems to be suitable for the development of flow cytogenetics and the technology can be applied to the physical mapping of DNA sequences, the targeted isolation of molecular makers and the construction of chromosome- and arm-specific DNA libraries. These approaches should facilitate the analysis of the complex genome of hexaploid bread wheat.
TL;DR: In most cases of AML, conventional cytogenetic study reliably detects chromosomal abnormalities, and this method should not be replaced by FISH, but FISH should be used as a complementary method for the detection of more subtle abnormalities.
Abstract: PURPOSE: To prospectively compare cytogenetic and molecular cytogenetic analysis for the detection of the most relevant chromosome abnormalities in a large series of patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Two hundred forty consecutive adult patients with AML entered onto the multicenter treatment trial AML HD93 were studied. Chromosome banding and fluorescence in situ hybridization (FISH) applying a comprehensive set of genomic DNA probes were performed in a single reference laboratory. RESULTS: Two cases of inv(16), three cases of t(11q23), and three cases of t(8;21)var were only detected by molecular cytogenetics. By FISH, aberrations were identified in three cases with normal karyotypes: inv(16), −Y (in a patient with low metaphase yield on chromosome banding) and a 12p microdeletion. Additional aneuploidies, in particular +8q and +11q, were diagnosed by FISH; however, virtually all these aberrations occurred in patients with complex karyotypes or as an additional abnormality...
TL;DR: The role of KIT mutations and chromosomal rearrangements in the pathogenesis of GIST/GIPACTs are more complex than previously recognized.
Abstract: Gastrointestinal stromal (pacemaker cell) tumors (GIST/GIPACTs) are frequently associated with activating KIT mutations, primarily of exon 11 and rarely of exons 9 and 13, as well as certain chromosome rearrangements. Reports regarding the frequency and prognostic significance of KIT mutations are conflicting and few cases have been completely sequenced. Furthermore, there are few detailed analyses of chromosome alterations in GIST/GIPACTs. In a detailed analysis of 14 GIST/GIPACTs from 12 patients, we found a wider spectrum of KIT mutations than previously reported, including 11 different in-frame mutations involving exons 11, 14, and 15. No mutations were detected in four malignant tumors. The shorter (GNNK−) KIT isoform was preferentially expressed. Cytogenetic and spectral karyotype analyses of 10 tumors revealed clonal abnormalities in eight tumors; the most common were terminal 1p deletions and losses of chromosomes 14 and/or 22. Neither KIT mutation status nor chromosome aberrations correlated with tumor phenotype or clinical behavior in our series. Collectively, these findings indicate that the role of KIT mutations and chromosomal rearrangements in the pathogenesis of GIST/GIPACTs are more complex than previously recognized.
TL;DR: Transmission of Y chromosome microdeletions could potentially have severe clinical consequences other than male infertility, such as the development of sexual ambiguities and Turner stigmata.
TL;DR: In AML with a complex aberrant karyotype, loss of tumor‐suppressor genes is a more important mechanism of leukemogenesis than activation of oncogenes, and that gene‐dosage effects may play a significant role in the pathogenesis of this AML subtype.
Abstract: Patients with acute myeloid leukemia (AML) and a complex aberrant karyotype have a poor outcome despite intensive antileukemic treatment. The aim of this study was to analyze in detail the genetic abnormalities in this subgroup of AML. Therefore, 125 AML cases with complex aberrant karyotype detected by G-banding were examined in addition with 24-color FISH and FISH with locus-specific probes for EGR1 (5q31), D7S522 (7q31), and TP53 (17p13), given that these regions are known to be commonly deleted in AML with a complex aberrant karyotype. The number of chromosome abnormalities per case varied from 3 to 30 (median 10). A gain of a whole chromosome was observed 131 times, with +8 (n = 30), +10 (n = 11), and +22 (n = 10) being the most frequent trisomies. A loss of a whole chromosome occurred 128 times. The chromosomes most often lost were 7 (n = 25), 18 (n = 24), and 17 (n = 17). Structural aberrations, leading to a gain or loss of chromosomal material, were detected 104 times and 433 times, respectively. Aberrations including only two chromosomes that seemed to be balanced were found only 19 times. Losses resulting from structural abnormalities most frequently involved 5q (n = 100), 17p (n = 47), and 12p (n = 29), whereas gains of 11q (n = 21), 21q (n = 19), and 8q (n = 11) were observed. Using locus-specific probes, deletions of the EGR1 locus (5q31), of 7q31, and the TP53 gene were observed in 103 (82%), 57 (46%), and 66 (53%) cases, respectively. In conclusion, in AML with a complex aberrant karyotype, loss of chromosomal material was observed much more often than gain. Unbalanced rearrangements leading to loss of chromosomal material are much more frequent than loss of whole chromosomes. These data suggest that in AML with a complex aberrant karyotype, loss of tumor-suppressor genes is a more important mechanism of leukemogenesis than activation of oncogenes, and that gene-dosage effects may play a significant role in the pathogenesis of this AML subtype.
Journal Article•
TL;DR: A critical role of the HMGA2 overexpression in the generation of prolactin-secreting pituitary adenomas in humans is suggested.
Abstract: Trisomy of chromosome 12 is a nonrandom chromosomal change in pituitary adenomas, particularly prolactinomas. This and the finding that prolactin-secreting pituitary adenomas develop in transgenic mice overexpressing the wild-type HMGA2 gene (which maps to 12q14-15) prompted us to investigate HMGA2 rearrangements and expression in human prolactinomas. By dual-color interphase fluorescence in situ hybridization analysis using HMGA2-specific PACs and BACs, we found that the HMGA2 locus was amplified in seven of the eight prolactinoma samples examined. The cytogenetic manifestations of elevated HMGA2 concentrations ranged from simple trisomy to tetrasomy 12 and der(12) chromosomes to marker chromosomes bearing 12q14-15-derived regions. Reverse transcription-PCR, Western blot and immunohistochemical analysis showed HMGA2 overexpression in a number of prolactinomas bearing rearrangement of regions 12q14-15. These data suggest a critical role of the HMGA2 overexpression in the generation of prolactin-secreting pituitary adenomas in humans.
TL;DR: In this paper, the authors report cytogenetic findings in 19 c-Kit-positive gastrointestinal stromal tumors (GISTs) that represent a heterogenous group of mesenchymal neoplasms with respect to site, histology, and biologic behavior.
TL;DR: In this article, the authors examined factors that might influence the occurrence of constitutional translocations in the population and identified chromosome size as the major determinant of translocation frequency, which probably reflects the large target size for double-strand breakage and repair presented by the largest chromosomes.
Abstract: Translocations are the most frequent chromosome structural aberration in the human population, yet little is known about their aetiology Here, factors that might influence the occurrence of constitutional translocations in the population are examined By analysing >10000 translocations from two large databases of cytogenetic abnormalities, chromosome size is identified as the major determinant of translocation frequency This probably reflects the large target size for double-strand breakage and repair presented by the largest chromosomes There is also evidence for selection against translocations that involve breakage through the most gene-dense chromosomes Lastly, it is suggested that nuclear organization of chromosomes impinges on the frequency of translocations amongst the smallest autosomes
TL;DR: Evaluated cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours.
Abstract: Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution.
TL;DR: In this article, spectral karyotyping was used to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding.
Abstract: We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for −21 (eight of eight patients), −5 (five of six patients), −20 (seven of nine patients), and −18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 21 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized. © 2002 Wiley-Liss, Inc.
TL;DR: Premature entry of cells into mitosis suggests that a gene involved in cell-cycle regulation is mutated in these siblings, and the entire cell cycle is not prolonged, compared with that in healthy control subjects.
Abstract: We report a novel autosomal recessive disorder characterized by premature chromosome condensation in the early G2 phase. It was observed in two siblings, from consanguineous parents, affected with microcephaly, growth retardation, and severe mental retardation. Chromosome analysis showed a high frequency of prophase-like cells (>10%) in lymphocytes, fibroblasts, and lymphoblast cell lines with an otherwise normal karyotype. 3H-thymidine-pulse labeling and autoradiography showed that, 2 h after the pulse, 28%–35% of the prophases were labeled, compared with 9%–11% in healthy control subjects, indicating that the phenomenon is due to premature chromosome condensation. Flow cytometry studies demonstrate that the entire cell cycle is not prolonged, compared with that in healthy control subjects, and compartment sizes did not differ from those in healthy control subjects. No increased reaction of the cells to X-irradiation or treatments with the clastogens bleomycin and mitomycin C was observed, in contrast to results in the cell-cycle mutants ataxia telangiectasia and Fanconi anemia. The rates of sister chromatid exchanges and the mitotic nondisjunction rates were inconspicuous. Premature entry of cells into mitosis suggests that a gene involved in cell-cycle regulation is mutated in these siblings.
TL;DR: Both the chromosome and molecular findings suggest that genome reshuffling might have occurred by manipulation or mating of the clones.
Abstract: Polyploid gibel carp, Carassius auratus gibelio, is an excellent model system for evolutionary genetics owing to its specific genetic background and reproductive modes. Comparative karyotype studies were performed in three cultured clones, one artificially manipulated group, and one mated group between two clones. Both the clones A and P had 156 chromosomes in their karyotypes, with 36 metacentric, 54 submetacentric, 36 subtelocentric, 24 acrocentric, and six small chromosomes. The karyotype of clone D contained 162 chromosomes, with 42 metacentric, 54 submetacentric, 36 subtelocentric, 24 acrocentric, and six small chromosomes. All the three clones had six small chromosomes in common. Group G, being originated from the clone D by artificial manipulation, showed supernumerary microchromosomes or chromosomal fragments, in addition to the normal chromosome complement that was identical to the clone D. The offspring from mating between clones D and A had 159 chromosomes. Comparing with the clone A, the DA offspring showed three extra metacentric chromosomes. In addition, variable RAPD fingerprint patterns and unusual SCAR marker inheritance were, respectively, detected among individuals of artificial group G and in the mated DA offspring. Both the chromosome and molecular findings suggest that genome reshuffling might have occurred by manipulation or mating of the clones.
TL;DR: FISH results suggest that only 46,XY cells can undergo meiosis, and the aneuploidy rate among post-meiotic cells for chromosomes X,Y and 18 was 6.75%.
Abstract: BACKGROUND: A testis biopsy was performed for four non-mosaic 47,XXY azoospermic patients. Spermatozoa were found in three cases and frozen before ICSI. We analysed the various cells found in the four samples by multicolour fluorescence in-situ hybridization (FISH), to evaluate the meiosis and spermatogenesis possibilities of the 47,XXY and 46,XY testis cell lines, and to estimate aneuploidy rate in the resulting spermatids and spermatozoa. METHODS AND RESULTS: Testis diploid cells (either somatic or premeiotic), meiotic, and post-meiotic haploid germ cells were hybridized with probes for chromosomes X, Y and 18. The only patient with no spermatozoa had a homogeneous diploid XXY constitution in the testis; the three other patients presented two cell populations (46,XY and 47,XXY) among their diploid testis cells. All the observed pachytene figures were XY; no XXY pachytene figure was found. The aneuploidy rate among post-meiotic cells for chromosomes X,Y and 18 was 6.75% (5/74). This rate was 1.5% (2/133) for control. Three couples underwent ICSI; four attempts were made, one healthy baby was born. CONCLUSION: FISH results suggest that only 46,XY cells can undergo meiosis.
TL;DR: The occurrence of the nondisjunction of chromosomes as well as ongoing rearrangement processes in utero were confirmed by the presence of all 3 IgH rearrangements in neonatal blood spots, providing the first evidence that hyperdiploidy formation is an early event in leukemogenesis in these leukeMias.
TL;DR: Using electrophoretic techniques for karyotype analysis, a highly dimorphic chromosome pair that determines mating compatibility is shown to occur in populations of the fungus Microbotryum violaceum, substantiates the evolution of such dimorphism as a general feature associated with haploid determination of mating compatibility.
Abstract: Fungi often mate as haploids, and sex chromosomes (i.e., mating-type chromosomes) that are dimorphic for their size or overall DNA content have never been reported in this kingdom. Using electrophoretic techniques for karyotype analysis, a highly dimorphic chromosome pair that determines mating compatibility is shown to occur in populations of the fungus Microbotryum violaceum. This substantiates the evolution of such dimorphism as a general feature associated with haploid determination of mating compatibility, which previously had been known only in haplodioecious plants (mosses and liverworts). Size-dimorphic sex chromosomes are present in a lineage of M. violaceum native to Europe, as well as a lineage native to North America. However, they are very different in size between these lineages, indicating either independent evolution of the dimorphism or a large degree of divergence since their isolation. Several DNA sequences that show sequence similarity to transposons were isolated from these sex chromosomes.
TL;DR: A detailed description of chromosomal translocations occurring in MCC is provided that could be useful to direct future intensive investigation of these chromosomal regions.
Abstract: Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Cytogenetic studies have indicated that deletions and unbalanced translocations involving chromosome 1 short arm material occur in 40% of the investigated cases. Recurrent chromosomal imbalances detected by comparative genomic hybridization (CGH) analysis were loss of 3p, 10q, 13q and 17p and gains of 1q, 3q, 5p and 8q. In order to study genomic aberrations occurring in MCC in further detail, we combined karyotyping, CGH and multiplex-fluorescence in situ hybridization (M-FISH), a strategy that proved to be successful in the analysis of other malignancies. Analysis of 6 MCC cell lines and 1 MCC tumor revealed mostly near-diploid karyotypes with an average of 5 chromosomal rearrangements. The observed karyotypic changes were heterogeneous, with 3–27 breakpoints per case, leading to imbalance of the involved chromosomal regions that was confirmed by CGH. Chromosomal rearrangements involving the short arm of chromosome 1, the long arm of chromosome 3 and gain of 5p material were the most frequently observed abnormalities in our study. In keeping with previous observations, this series of MCCs showed no evidence for high-level amplification. We provid a detailed description of chromosomal translocations occurring in MCC that could be useful to direct future intensive investigation of these chromosomal regions. © 2002 Wiley-Liss, Inc.
TL;DR: Findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
Abstract: Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
TL;DR: The observation of similar chromosomal abnormalities in both skeletal and extraskeletal mesenchymal chondrosarcoma supports a genetic as well as histopathologic relationship between these anatomically distinct neoplasms.
TL;DR: It is suggested that the majority of TS karyotype are caused by paternal meiotic errors that generate abnormal sex chromosomes, and that most 45,X cells are generated by mitotic loss of these abnormal sex chromosome, resulting in maternal X dominance in these cells.
Abstract: The parental origin of the X chromosome of 45,X females has been the subject of many studies, and most of them have shown that the majority (60-80%) of the X chromosomes are maternal in origin. However, studies on the parental origin of normal X chromosomes are relatively limited for Turner syndrome (TS) females with sex chromosome aberrations. In this study, we used PCR-based typing of highly polymorphic markers and an assay of methylation status of the androgen receptor gene to determine the parental origin of normal X chromosomes in 50 unbiased TS females with a variety of karyotypes. Our results showed a higher paternal meiotic error rate leading to the generation of abnormal sex chromosomes, especially in the case of del(Xp) and abnormal Y chromosomes. Isochromosome Xq and ring/marker X chromosomes, on the other hand, were equally likely the result of both maternal and paternal meiotic errors. A thorough review of previous results, together with our data suggests, that the majority of TS karyotype are caused by paternal meiotic errors that generate abnormal sex chromosomes, and that most 45,X cells are generated by mitotic loss of these abnormal sex chromosomes, resulting in maternal X dominance in these cells.