Showing papers on "Karyotype published in 1989"
TL;DR: It is found that in 4 XX males lacking ZFY, there is exchange of Y-specific sequences next to the pseudoautosomal boundary, redefining the region in which TDF must lie.
Abstract: IN mammals, the testis determining gene (TDF), present on the Y chromosome, induces the undifferentiated gonads to form testes1. The position of TDF on the human Y chromosome has been defined by analysing the genomes of XX males and XY females2, generated by abnormal genetic exchange between the X and Y chromosomes in male meiosis3. In this way TDF has been localized close to the pseudoautosomal region shared by the sex chromosomes, in the distal Y-specific region. A recently cloned human gene, ZFY, has many features indicating that it is TDF4–6. For example, ZFY encodes a protein with many features of a transcription factor including a domain with multiple 'zinc-finger' motifs4–6. Less consistent with ZFY being TDF, however, is the presence of a very similar gene, ZFX, on the X chromosome4,7, and the presence of a sequence related to ZFY on autosomes in marsupials8. We now report on analysis of XX males lacking ZFY. In these individuals, the male phenotype could be explained by a mutation in a gene 'downstream' of ZFY in the sex-determining hierarchy; but in that case there should be no exchange of material between the X and Y chromosomes. We find on the contrary that in 4 XX males lacking ZFY, there is exchange of Y-specific sequences next to the pseudoautosomal boundary, redefining the region in which TDF must lie.
299 citations
TL;DR: This translocation between chromosomes 1 and 14 may identify a gene for which the name SCL (stem-cell leukemia) is proposed that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
Abstract: We have studied a leukemic stem-cell line, DU.528, that is able to differentiate into myeloid and lymphoid cells. The leukemic cells have a translocation between chromosomes 1 and 14, t(1;14)(p33;q11), which we have molecularly cloned and sequenced. Initial screening used joining (J)-segment probes from the T-cell receptor (TCR) alpha- and delta-chain loci. In apparent concert with the translocation, a deletion has occurred between delta-chain diversity (D)-region genes D delta 1 and D delta 2. D delta 2 was observed on derivative chromosome 1 [der(1)] and D delta 1 on der(14) with a deletion of the intervening 10 kilobases of germ-line DNA. The nature of the D delta 1-D delta 2 deletional event implicates a lymphoid recombinase in the mechanism of the translocation. As a consequence of the translocation, an unusual fusion transcript was generated. Probes from chromosome 1 detected a previously unreported transcript in RNA from both the cell line and the patient. A chromosome 14 probe identified the same transcript, thus confirming a fusion transcript derived from both chromosomes 1 and 14. This translocation may identify a gene for which we propose the name SCL (stem-cell leukemia) that is important for hemopoietic development and oncogenesis and that has been disrupted or altered in this stem-cell line.
270 citations
TL;DR: The size of the common duplicated region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis of Down syndrome.
Abstract: The duplication of a specific region of chromosome 21 could be responsible for the main features of Down syndrome. To define and localize this region, we analyzed at the molecular level the DNA of two patients with partial duplication of chromosome 21. These patients belong to two groups of Down syndrome patients characterized by different partial trisomies 21: (i) duplication of the long arm, proximal to 21q22.2, and (ii) duplication of the end of the chromosome, distal to 21q22.2 We assessed the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) and found that D21S55 was duplicated in both cases. By means of pulsed-field gel analysis and with the knowledge of regional mapping of the probes D21S17, D21S55 and ETS2, we estimated the size of the common duplicated region to be between 400 and 3000 kilobases. This region, localized on the proximal part of 21q22.3, is suspected to contain genes the overexpression of which is crucial in the pathogenesis of Down syndrome.
244 citations
Journal Article•
TL;DR: The data show that more than one specific chromosomal site may be involved in the development of human renal cell carcinomas, and it is proposed that the 3p13-pter segment was identified as the minimal common deletion.
Abstract: The karyotype of 75 sporadic, nonpapillary renal cell carcinomas was analyzed using chromosome banding techniques. Sixty-five tumors had near-diploid stemlines, and ten had near-triploid or near-tetraploid stemlines. Aberration of chromosome 3 was detected in 71 cases. The nonrandom changes on chromosome 3 were monosomy 3, terminal deletions, or unbalanced translocations; the 3p13-pter segment was identified as the minimal common deletion. The rearrangement of chromosome 3p was the only karyotype change in 13 tumors. Abnormalities of chromosome 5 resulting in trisomy for the 5q22-qter region were found in 36 cases, while the loss of 14q22-qter segment was observed in 34 tumors. Trisomy for chromosome 7 was detected in 17 cases, and monosomy 8 and 9 occurred 14 times each. Our data show that more than one specific chromosomal site may be involved in the development of human renal cell carcinomas.
211 citations
Journal Article•
TL;DR: Some karyotype alterations in renal cell carcinomas could perhaps be regarded as a genetic mechanism responsible for the phenotype of conversed tubular cells.
Abstract: Most renal cell carcinomas are characterized by constant loss of the 3p13-pter chromosome segment and a frequent gain of the 5q22-qter segment. A comparative histologic and cytogenetic investigation of large series of renal cell carcinomas now shows that purely papillary tumors differ from the more common nonpapillary form not only in their morphologic characteristic, but also in karyotype changes observed. All of the 11 papillary tumors of this study failed to show any rearrangement of the critical 3p segment, and trisomy of the 5q22-qter segment has never been found. The gain of chromosome 17 was detected only in papillary renal cell carcinomas. Other nonrandom karyotype changes occurred with the same incidence in both types of tumor. Thus, some karyotype alterations in renal cell carcinomas could perhaps be regarded as a genetic mechanism responsible for the phenotype of conversed tubular cells.
183 citations
TL;DR: Given the results, which in some patients were in disagreement with their cytogenetic descriptions, trisomy for locus D21S13 through locusD21S58 is excluded from significant contribution to many Down syndrome features, the minimal chromosome region necessary in triplicate to result in the Down syndrome phenotypes in the patients characterized.
182 citations
Journal Article•
TL;DR: The association of a reciprocal translocation involving the short arm of chromosomes 2 and 5 and the long arm of chromosome 5, t(2;5)(p23;q35), with Ki-1 positive anaplastic large cell lymphoma is reported.
Abstract: In lymphoid neoplasms, nonrandom cytogenetic abnormalities correlate with clinical, morphologic and immunophenotypic features. A subtype of non-Hodgkin's lymphoma, which expresses the Ki-1 antigen (CD30) and has distinct morphologic and clinical features, has recently been described. We now report the association of a reciprocal translocation involving the short arm of chromosome 2 (band p23) and the long arm of chromosome 5 (band q35), t(2;5)(p23;q35), with Ki-1 positive anaplastic large cell lymphoma. Rearrangement of the genes that are located at the breakpoints on chromosomes 2 and 5 may be a critical step in the pathogenesis of this lymphoma.
173 citations
TL;DR: It is proposed that localized and Stage IV‐S neuroblastomas can be classified as one disease category, and that patients with near diploid or hypotetraploid karyotypes are clinically distinct from those having hyperdiploids or near triploidKaryotypes.
Abstract: The relationship between cytogenetic findings and prognosis in 51 pediatric patients with neuroblastoma is described. Patients were classified into the following four groups based on karyotypic findings: (1) near diploidy, 42 to 47 chromosomes (n = 11); (2) hyperdiploidy, 50 to 56 chromosomes (n = 4); (3) near triploidy, 60 to 77 chromosomes (n = 33); and (4) hypotetraploidy, 80 to 83 chromosomes (n = 3). Patients with near diploid or hypotetraploid karyotypes also had several structural abnormalities including marker chromosome 1, with or without double minutes (DM) or homogeneously staining regions (HSR). Most of these patients were 1 year of age or older and had advanced tumors. The patients who were in the hyperdiploid or near triploid category had few structural abnormalities; all of them, except one, were younger than 1 year of age, had localized tumors, and are long-term, disease-free survivors. Kaplan-Meier analysis of survival rates disclosed a significant difference favoring the latter group (P less than 0.001). N-myc gene amplification was found in five patients of the former group but in no patients of the latter group. The presence or absence of DM or HSR in the former group had no statistically demonstrable effect on survival. However, the presence of marker chromosome 1 appears to indicate a poor prognosis. Five patients with Stage IV-S disease had near triploid abnormalities similar to findings in patients with localized tumors. We propose that localized and Stage IV-S neuroblastomas can be classified as one disease category, and that patients with near diploid or hypotetraploid karyotypes are clinically distinct from those having hyperdiploid or near triploid karyotypes. We consider that chromosomal pattern is a more influential prognostic factor than age, disease stage, or N-myc gene amplification.
170 citations
TL;DR: The high frequency of i(12p) in series of studies and in those of others indicates that it probably occurs as a very early defect in the development of these tumors, and further studies of chromosome 12 in males with these tumors are warranted.
Abstract: Twenty-nine tumor specimens were obtained from 24 males with germ cell tumors. All primary sites and histologies were represented. An isochromosome of the short arm of chromosome 12 [i (12p)] was found in 20 specimens obtained from 16 patients, a 46,XY normal karyotype was present in seven specimens, and one specimen was a cytogenetic failure. The i(12p) was found in tumors from all primary sites and in all histologies, including a choriocarcinoma. The presence of three or more additional copies of 12p was associated with a statistically significant greater likelihood of treatment failure. With diagnostic and possibly prognostic importance in germ cell tumors in males, the high frequency of i(12p) in our series of studies and in those of others indicates that it probably occurs as a very early defect in the development of these tumors. Further studies of chromosome 12 in males with these tumors are warranted.
162 citations
TL;DR: Several groups of children with less than 15% chance of cure who clearly need to be treated as high-risk patients at diagnosis are identified, and future studies of patients who have received risk-adapted therapy based on these chromosome data are needed to determine if more intensive treatment will improve the outlook of patients with cytogenetically unfavorable types of ALL.
146 citations
TL;DR: Banding of metaphase chromosomes is an invaluable aid to analysing the complex genomes of vertebrates, but the biochemical basis for this phenomenon is poorly understood.
TL;DR: Since micronuclei were more efficiently induced in these hybrids compared to parental human fibroblasts by colcemid treatment, the transfer of neo‐tagged human chromosomes in the hybrids was performed via microcell fusion.
Abstract: Normal human fibroblasts (MRC-5 or NTI-4) were transfected with pSV2-neo plasmid DNA. Fifty G418-resistant fibroblast clones were isolated and independently fused to mouse A9 cells. The cell hybrids were selected and isolated in the medium containing G418 plus ouabain. Since micronuclei were more efficiently induced in these hybrids compared to parental human fibroblasts by colcemid treatment, the transfer of neo-tagged human chromosomes in the hybrids to mouse A9 cells was performed via microcell fusion. Two hundred A9 microcell hybrids were isolated and karyotyped. Among them, thirteen microcell clones, each containing a single human chromosome 1, 2, 5, 6, 7, 8, 10, 11, 12, 15, 18, 19 or 20 were established. Isozyme analyses conformed the presence of each human chromosome in these A9 microcell clones. The results of Southern blot and chromosomal in situ hybridization analyses indicate that the human chromosomes in these clones were tagged with pSV2-neo plasmid DNA.
TL;DR: It is reported that antibodies raised against a highly purified and biochemically well characterized nonhistone "High-Mobility Group" protein, HMG-I, specifically localize this protein to the G-bands in mammalian metaphase chromosomes.
Abstract: Mammalian metaphase chromosomes can be identified by their characteristic banding pattern when stained with Giemsa dye after brief proteolytic digestion. The resulting G-bands are known to contain regions of DNA enriched in A/T residues and to be the principal location for the L1 (or Kpn 1) family of long interspersed repetitive sequences in human chromosomes. Here we report that antibodies raised against a highly purified and biochemically well characterized nonhistone "High-Mobility Group" protein, HMG-I, specifically localize this protein to the G-bands in mammalian metaphase chromosomes. In some preparations in which chromosomes are highly condensed, HMG-I appears to be located at the centromere and/or telomere regions of mammalian chromosomes as well. To our knowledge, this is the first well-characterized mammalian protein that localizes primarily to G-band regions of chromosomes.
TL;DR: A German family carrying a constitutional translocation (3;6) (p13;q25.1) in 3 consecutive generations and the only member of the family over 50 years of age and carrying the translocation developed multiple bilateral renal cell carcinomas is described.
Abstract: We describe a German family carrying a constitutional translocation (3;6) (p13;q251) in 3 consecutive generations The only member of the family over 50 years of age and carrying the translocation developed multiple bilateral renal cell carcinomas We performed chromosome analysis of 4 out of 5 primary tumours, which were characterized by different clonal karyotypes The constitutionally translocated 3p13-pter segment was lost with or without the receptor chromosome 6 in each tumour Additional karyotypic changes were trisomy 5, 7 and 18, monosomy 14 and 21, and loss of the Y chromosome, all karyotype changes occurring frequently in sporadic non-papillary RCCs This case is discussed with regard to the possible role of suppressor gene inactivation by constitutional translocation in the development of familial renal cancers
TL;DR: This study identified novel abnormalities that have not been reported by others and disclosed an unusual heterogeneity of chromosome 16 abnormalities with respect to their distribution among FAB subtypes, their association with marrow eosinophilia, and their participation with other chromosomes in translocations.
TL;DR: It was found that each strain had a unique, reproducible pattern of chromosome bands which could potentially be used for strain polymorphism studies, and the ribosomal DNA genes were found on one of the larger C. neoformans chromosomes.
Abstract: Chromosomes from Cryptococcus neoformans, an encapsulated yeast pathogen, were separated by contour-clamped homogeneous field gel electrophoresis. Seven strains representing all four serotypes were studied. It was found that each strain had a unique, reproducible pattern of chromosome bands which could potentially be used for strain polymorphism studies. There were between 10 and 12 chromosomes in the strains studied, with an approximate genomic size of 15,000 to 17,000 kilobases. Chromosome separation also could be used to assign locations for cloned genes, and the ribosomal DNA genes were found on one of the larger C. neoformans chromosomes. The technique of electrophoretic karyotyping should be helpful for genetic and molecular investigations into the biology of C. neoformans.
TL;DR: It is suggested here that maintenance of the normal diploid cell depends on the presence of two copies of specific genes; a change in gene dosage of one or more of these genes, by chromosome nondisjunction or rearrangement, may trigger a general loss of accuracy in chromosome segregation at mitosis.
TL;DR: Host cell factors act together with regulatory genes of the human immunodeficiency virus to control virus production and reveal a 94% concordance between human chromosome 12 and HIV gene expression.
Abstract: Host cell factors act together with regulatory genes of the human immunodeficiency virus (HIV) to control virus production. Human-Chinese hamster ovary hybrid cell clones were used to probe for human chromosomes involved in regulating HIV gene expression. DNA transfection experiments showed that 4 of 18 clones had high levels of HIV gene expression measured by both extracellular virus production and transactivation of the HIV long terminal repeat in the presence of the trans-activator (tat) gene. Karyotype analyses revealed a 94% concordance (17/18) between human chromosome 12 and HIV gene expression. Other chromosomes had an 11 to 72% concordance with virus production.
TL;DR: The initial clinical features associated with translocations involving the 11q23 chromosomal region may define a distinct subtype of ALL, and whether the constellation of findings relates to a breakpoint at 11Q23 per se or to the specific translocation will require further study.
TL;DR: The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo, and some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected.
Journal Article•
TL;DR: The finding of a recurring translocation site involving the long arm of chromosome 6 (6q) in malignant melanoma and molecular analysis of the translocation breakpoints may identify a gene(s) which plays a role in melanoma tumorigenesis.
Abstract: The recognition of recurring sites of chromosome change in human cancers has pinpointed the location in the genome of several important growth-regulatory sequences (e.g., cellular oncogenes). This report details the finding of a recurring translocation site involving the long arm of chromosome 6 (6q) in malignant melanoma. We have observed a translocation (t) between chromosomes 1 and 6 in five different cases of malignant metastatic melanoma. All five melanomas evidencing t(1;6) involved band regions 6q11-13, while two different regions of chromosome 1 (p22, q12-q21) were shown to be translocated to 6q. In reviewing previously published cases of melanoma, an additional two cases of t(1;6) and 13 cases of other translocations to 6q11-13 have been identified. Chromosome 6q contains several biologically important gene sequences including the proto-oncogenes ros, myb, and mas1. However, based on current mapping studies, the breakpoint of this translocation (6q11-13) is not within the region encoding these sequences. By analogy to other systems, molecular analysis of the translocation breakpoints may identify a gene(s) which plays a role in melanoma tumorigenesis.
TL;DR: It is suggested that this loss of heterozygosity for genetic material on chromosome 3p or on 11p is nonrandom and important in the development of a major subset of testicular neoplasms.
TL;DR: Structural chromosomal abnormalities in cases of ALL with greater than 50 chromosomes may define a biologically different form of leukemia characterized by increased likelihood of drug resistance.
TL;DR: It is concluded that the B chromosomes of C. capillaris are isochromosomes with active rRNA genes located near both telomeres, and both darkly-staining nucleolar constrictions of chromosomes No. 3 and silver deposits at the telomere of Bs.
Abstract: A non-radioactive in situ hybridization method using biotin-labelled rDNA has made it possible to localize rRNA genes not only at the secondary constriction in both homologous chromosomes No. 3 of Crepis capillaris but also in the B chromosomes occurring in the plants employed. Very clear dot-like rDNA signals at the telomeres of both arms were observed in all B chromosomes. Histochemical silver staining, which is indicative of transcriptional activity of rRNA gene clusters, resulted in both darkly-staining nucleolar constrictions of chromosomes No. 3 and silver deposits at the telomeres of Bs. We conclude that the B chromosomes of C. capillaris are isochromosomes with active rRNA genes located near both telomeres.
TL;DR: Five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome are reported on, characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency.
Abstract: We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a ''bird-like'' face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia normore » telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal.« less
TL;DR: An electrophoretic molecular karyotype has been established for an industrial strain of Cephalosporium acremonium using transverse alternating field electrophoresis as discussed by the authors.
TL;DR: A combination of DNA analysis and in situ hybridisation demonstrated that the mother has a previously unsuspected balanced reciprocal translocation between the tips of the short arms of chromosomes 1 and 16, and that the alpha-globin gene complex is included in the translocated segment.
TL;DR: The results suggest that most of the TGRI clusters consist of single, uninterrupted blocks of satellite DNA, close to the estimated total length of TGRI in the genome based on genomic reconstruction experiments.
Abstract: A karyotype of tomato mitotic chromosomes was constructed based on in situ hybridization to a 162-bp telomeric DNA repeat, TGRI. Variation in the spatial and quantitative distribution of this repeat creates distinct patterns for most of the chromosomes, which along with other morphological characteristics (i.e., length and arm length ratio), allow the identification of each of the 12 mitotic chromosomes of tomato. The structure and physical size of the TGRI clusters were further investigated by means of pulsed-field gel electrophoresis. Approximately 30 hybridizing fragments were observed in the range of 25 to 1000 kb when high molecular weight DNA was digested with BglII and probed with TGRI. The total molecular weight of these fragments is approximately 14 million bp, which is close to the estimated total length of TGRI in the genome (12.5 million bp) based on genomic reconstruction experiments. The results suggest that most of the TGRI clusters consist of single, uninterrupted blocks of satellite DNA. ...
TL;DR: The results demonstrate that Barrett's esophagus is frequently characterized by clonal proliferation of karyotypically abnormal cells.
TL;DR: A detailed analysis of the cytogenetic features of leukemic cells from 104 immunologically classified acute lymphoblastic leukemia (ALL) cases expands the current knowledge about immunophenotype-karyotype associations in ALL.