Showing papers on "Chromosome 22 published in 1983"

Localization of the c- abl oncogene adjacent to a translocation break point in chronic myelocytic leukaemia

Abstract: The human c-abl oncogene maps within the region (q34-qter) of chromosome 9 which is translocated to chromosome 22, the Philadelphia (Ph′) chromosome, in chronic myelocytic leukaemia (CML) The position of the Ph′ chromosomal break point is shown to be variable and, in one CML patient, has been localized immediately 5′ of, or within, the c-abl oncogene A DNA restriction fragment corresponding to this site has been molecularly cloned and shown to represent a chimaeric fragment of DNA from chromosomes 9 and 22

Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome

Abstract: The inheritance of two restriction fragment length polymorphisms (RFLPs) on the short arm of the human X chromosome has been studied relative to Duchenne muscular dystrophy. This provides a partial genetic map of the short arm of the human X chromosome between Xp110 and Xp223. The data were derived from the segregation between a RFLP located at Xp21-Xp223, the DMD locus, and a RFLP located at Xp110-Xp113. The genetic distance from Xp110 to Xp223 was found to be approximately 40 centimorgans (cM). This provides experimental confirmation that 1cM corresponds to approximately 1,000 kilobase pairs of DNA for this region of the human X chromosome. Our data confirm that the DMD mutation lies between Xp223 and Xp110. The availability of flanking probes surrounding the DMD locus will assist in the ordering of further DNA sequences relative to the mutation.

Isolation and characterization of a major tandem repeat family from the human X chromosome

Abstract: We report the identification and characterization of a family of repeated restriction fragments whose molecular organization is apparently specific to the human X chromosome. This fragment, identified as an ethidium bromide-staining 2.0 kilobase (kb) band in BamHI-digested DNA from a Chinese hamster-human somatic cell hybrid containing a human X chromosome, has been cloned into pBR325 and characterized. The 2.0 kb repeated family has been assigned to the Xp11 leads to Xq12 region on the X by Southern blot analysis of somatic cell hybrids and is predominantly arranged in tandem clusters of up to seven 2.0 kb monomers. Homologous DNA sequences, not organized as 2.0 kb BamHI fragments, are found elsewhere on the X chromosome and on at least some autosomes, but are not found on the Y chromosome. From a dosing experiment using various amounts of the cloned repeat, we estimate that there are 5,000-7,500 copies of the 2.0 kb BamHI repeat per haploid genome. Since the vast majority, if not all, of these are confined to the X chromosome, this repeated DNA family must account for 5-10% of all X chromosome DNA and must constitute the major sequence component of the pericentromeric region of the X.

Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562.

Abstract: Structural rearrangements of specific cellular sequences (c-onc genes) homologous to acute transforming retrovirus oncogenes (v-onc genes) have been recently described in various malignancies. Here we show that human cellular sequences (c-abl) homologous to the transforming sequences of the mouse Abelson leukemia virus (v-abl) are amplified some 4- to 8-fold in K-562, a Philadelphia chromosome-positive cell line derived from a patient with chronic myelogenous leukemia in blast crisis. Restriction analysis of K-562 and other human DNA samples reveals a significant rearrangements of the c-abl sequences in this cell line. In addition, investigation of v-abl-related cytoplasmic RNA reveals relatively high levels of these sequences in K-562 compared to other normal and leukemia cells. We have also observed that lambda light chain constant region immunoglobulin genes are amplified in K-562, whereas kappa light chain sequences exhibit no amplification. These results are discussed within the context of the possibility that these Philadelphia chromosome-positive cells exhibit a reciprocal translocation involving chromosome 9 (containing c-abl) and chromosome 22 (containing the lambda light chain genes).

Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia.

Abstract: NIARD (non-immunoglobulin-associated rearranging DNA) is located on mouse chromosome 15 at the break point of a commonly observed translocation event involving chromosomes 15 and 12 in murine plasmacytomas. The human cellular analogue of the v-myc oncogene of avian myelocytomatosis virus, strain MC-29, is known to reside on the distal end of human chromosome 8 and has been observed to translocate to chromosome 14 in Burkitt lymphomas. Using a cDNA clone specific for the transcript of the human c-myc gene (H c-myc), we show that the mouse c-myc (M c-myc) gene is contained within NIARD. NIARD-associated chromosome translocations occurred 1.3-2 kilobases (kb) 5′ of the mouse c-myc gene where NIARD recombines with the switch region of the Cα immunoglobulin gene in various murine plasmacytomas. The mouse c-myc encoding region within NIARD spanned <2.4 kb of DNA and expressed a low level of a 2.3-kb polyadenylylated RNA in BALB/c spleen. Increased (10- to 20-fold) levels of rearranged mouse c-myc transcripts (i.e., ≈1.8-2.1 kb) were observed in plasmacytomas that have NIARD-associated chromosome translocations. Human c-myc and NIARD probes detected DNA rearrangements of human c-myc in four of seven Burkitt lymphomas. DNA sequences adjacent to the human c-myc gene recombined with the Cμ immunoglobulin gene locus on chromosome 14 in several Burkitt lymphomas. The activation of the c-myc oncogene by chromosome translocation implicates its involvement in B-cell oncogenesis.

Nucleotide sequence and expression of human chromosome 21-encoded superoxide dismutase mRNA

Abstract: Cytoplasmic superoxide dismutase (SOD-1; EC 1.15.1.1) is encoded by human chromosome 21. The SOD-1 gene locus is located at chromosomal region 21q22, which is involved in Down syndrome. cDNA clones containing sequences of human SOD-1 were previously isolated. In the present study the nucleotide sequence of one clone, designated pS61-10, was determined. It contains 459 nucleotides representing the entire coding region and 95 nucleotides of the 3' untranslated region. In human cells two poly(A)-containing SOD-1 RNAs of 0.7 and 0.5 kilobases were detected. These two species are also present in monkey cells, whereas mouse cells contain only a 0.5-kilobase RNA. In a mouse/human hybrid line that contains chromosome 21 as the only human chromosome, the two human SOD-1 RNAs were detected, indicating that both are encoded by this chromosome. These RNAs were found in poly(A)-containing polysomal RNA and were translated in vitro to SOD-1 polypeptide; they are therefore functional mRNAs. In normal human fibroblasts 0.002-0.006% of the poly(A)-containing RNA was SOD-1 RNA. The level in monosomic 21 cells was 70% of this value and the level in fibroblasts from Down syndrome patients was about 2 times higher than normal.

Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C lambda locus in Burkitt.

Abstract: We have studied somatic cell hybrids between mouse myeloma cells and IARC-BL2 Burkitt lymphoma human cells carrying a t(8;22) chromosome translocation for the presence and expression of human immunoglobin lambda chains and for the c-myc oncogene. The results indicate that the c-myc oncogene remains on the 8q+ chromosome and that the excluded and rearranged C lambda allele translocates from chromosome 22 to this chromosome 8. As a result of the translocation, transcriptional activation of the c-myc oncogene on the rearranged chromosome 8 (8q+) occurs, while the c-myc oncogene in the normal chromosome 8 is transcriptionally silent. These findings suggest that the translocation of a rearranged immunoglobulin locus to the 3' side of an unrearranged c-myc oncogene may enhance its transcription and contribute to malignant transformation.

Human immune interferon gene is located on chromosome 12.

Abstract: A cDNA clone for human immune interferon (IFN-gamma) gene sequences, plasmid p69, was used to chromosomally map the IFN-gamma gene by detecting human IFN-gamma gene sequences in DNA isolated from human-rodent somatic cell hybrids. We were able to map the IFN-gamma gene by correlating the human chromosomes present in these hybrids with the human specific 8.8 and 2.0 kilobase pair fragments produced by EcoRI digestion of genomic DNA. Southern blot analysis of 37 hybrid cell lines indicated that the gene for IFN-gamma was on human chromosome 12. A hybrid containing a portion of chromosome 12 localized the IFN-gamma gene to the p1205 leads to qter region.

Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome.

Abstract: The mammalian sex chromosomes are thought to be related to each other by sharing a common origin. That is, the X and Y chromosomes originally evolved from a pair of chromosomes that only differed at the locus determining sexual differentiation1,2. For example, this evolutionary relationship is reflected during meiosis3 in chromosomal pairing between the tip of the human X chromosome short arm and the Y chromosome which presumably implies sequence homology4. However, compelling genetic evidence for functional homology between the mammalian X and Y chromosome is lacking. We describe here the localization of a gene to the tip of the short arm of the human X chromosome and evidence for a related gene on the Y chromosome.

Chromosome site for Epstein-Barr virus DNA in a Burkitt tumor cell line and in lymphocytes growth-transformed in vitro.

Abstract: The Epstein-Barr virus (EBV) genome stably persists in latently infected Burkitt tumor cells and growth-transformed B lymphocytes. These cells usually contain multiple copies of episomal viral DNA. Cytological hybridization of recombinant viral DNA fragments to metaphase chromosomes of two latently infected cell lines demonstrates that viral DNA localizes to both chromatids of one homologue of chromosome 1 in Namalwa, a Burkitt tumor cell line, and to both chromatids of one homologue of chromosome 4 in IB4, a cell line with transformed growth properties in vitro. The site of chromosome association remains stable in a clone of IB4 cells. Probes from five separate regions of the EBV genome hybridize to the same chromosome regions. A previously undescribed achromatic site is identified within the region of EBV chromosome cytological hybridization. These observations suggest that most or all of the EBV genome is integrated into the chromosomal DNA of Namalwa and IB4 cells. Although the chromosomal sites of EBV DNA association are among those regions with homology to the EBV IR3 repeated DNA sequence, EBV IR3 did not mediate recombination between EBV and chromosomal DNA.

Isolation of amplified DNA sequences from IMR-32 human neuroblastoma cells: facilitation by fluorescence-activated flow sorting of metaphase chromosomes

Abstract: Human neuroblastoma IMR-32 cells have large homogeneously staining regions (HSRs), primarily in the short arms of chromosome 1. We have constructed a recombinant phage library that is enriched for DNA present in the HSR of this chromosome by using fluorescence-activated flow sorting for initial chromosome purification. Eleven distinct cloned DNA segments were identified that showed significantly greater hybridization to IMR-32 genomic DNA, detected by Southern blotting, than to normal human genomic DNA. These sequences have also been localized to the HSR of chromosome 1 by in situ hybridization. Based on an approximate 50-fold sequence amplification for each cloned segment and a total HSR size of 150,000 kilobases, the amplified unit in the HSR is estimated to be 3,000 kilobases. Sequences homologous to all cloned HSR DNA segments were mapped to human chromosome 2 by using human-mouse hybrid cells. Further work using in situ hybridization demonstrated that cloned HSR segments were localized in the short arm of chromosome 2 in both normal and IMR-32 cells. Thus, the amplification of these sequences in IMR-32 cells may have involved transposition from chromosome 2 to chromosome I.

The human gene for the β subunit of nerve growth factor is located on the proximal short arm of chromosome 1

Abstract: Fragments of the recently cloned human gene for the beta subunit of nerve growth factor (beta-NGF) were used as hybridization probes in analyzing two sets of rodent-human somatic cell hybrids for the presence of human beta-NGF sequences. Results from the first set of hybrids assigned the human beta-NGF gene to chromosome 1 and ruled out the presence of sequences of comparable homology on any other chromosome. With the second set of hybrids, which contained seven different, but overlapping, regions of chromosome 1, the NGF locus was mapped to band 1p22.

Evolution of chromosomal regions containing transfected and amplified dihydrofolate reductase sequences.

Abstract: A modular dihydrofolate reductase gene has been introduced into Chinese hamster ovary cells lacking dihydrofolate reductase. Clones capable of growth in the absence of added nucleosides contain one to five copies of the plasmid DNA integrated into the host genome. Upon stepwise selection to increasing methotrexate concentrations, cells are obtained which have amplified the transforming DNA over several hundredfold. A detailed analysis of the chromosomes in three clones indicated the appearance of cytologically distinct chromosomal regions containing the amplified plasmid DNA which differ in surrounding sequence composition, structure, and location. Two of the clones examined have extensive, homogeneously staining regions. The DNA in these homogeneously staining regions replicates in the early part of the S phase. The amplified plasmid DNA is found associated at or near the ends of chromosomes or on dicentric chromosomes. We propose that integration of DNA may disrupt telomeric structures and facilitate the formation of dicentric chromosomes, which may then undergo bridge breakage-fusion cycles. These phenomena are discussed in relation to DNA transfer experiments and modes of gene amplification and chromosome rearrangement.

c-sis is translocated from chromosome 22 to chromosome 9 in chronic myelocytic leukemia

Abstract: By analysis of a series of somatic cell hybrids derived by fusion of either mouse or Chinese hamster cells with leukocytes from different chronic myelocytic leukemia (CML) patients or from normal donors, we have localized the human oncogene, c-sis, on the q11 to qter segment of chromosome 22 and demonstrated its translocation from chromosome 22 to chromosome 9 (q34) in CML.

[Chromosomal translocation (11; 22) in cell lines of Ewing's sarcoma].

Abstract: Chromosome studies were performed on 5 Ewing sarcoma cell lines. An identical reciprocal translocation t(11; 22) (q24; q12) was found in 4 cell lines established from 3 different tumors. These results, associated with those obtained at the same time and independently from fresh tumor cells, suggest that the translocation t(11; 22)(q24; q12) may be a chromosomal marker characteristic of Ewing sarcoma cells. This translocation involves the chromosome 22 on which the H-c-sis oncogene has been located; it could be used as a new tool for exploring the role of genetic transposition in the malignant cell transformation.

Nonrandom Chromosome Changes in Malignant Melanoma

Abstract: Chromosome aberrations were analyzed in 4 cases of malignant melanoma (MM) after disaggregation of the tumors with collagenase and short-term culture. In all cell cultures, the MM cells displayed a typical triangular spindle form. The chromosome number was near-diploid in one case and near-triploid in three cases. A total of 27 abnormal chromosomes were identified with the Giemsa banding technique. By far, the most common types of abnormalities were translocations, followed by deletions and isochromosomes. Chromosomes 1, 6, and 7 were found to be most frequently involved in structural aberrations. Markers originating from chromosomes 1 and 6 were found in all four cases, and abnormalities of chromosome 7 were found in three. Each marker chromosome was unique for a given case; no common markers for two or more cases were found. Based on the present results and an analysis of reports on the chromosomal constitution of MM cells in the literature, we suggest that abnormalities involving chromosomes 6 and 7 may be a characteristic feature of MM. Aberrations of chromosome 1, although common in MM, may be part of a general cytogenetic feature in human neoplasia.

Single-copy DNA sequences specific for the human Y chromosome

Abstract: Detailed studies of the role of the mammalian Y chromosome in primary sex determination are limited by the lack of available specific markers and by the fragmentary knowledge of its molecular organization. Y-derived unique DNA sequences could provide powerful analytical tools to probe directly the structure of the Y chromosome and provide a means of searching for specific expressed sequences. We report here the construction of a partial cosmid library of the human Y chromosome. From independent clones we have isolated 30 unrelated DNA probes that are free of highly repetitive sequences, and have examined their reaction pattern on male and female genomic blots. Of the 30 probes tested, six were specific for the Y chromosome. In addition, four probes gave a male-female differential hybridization pattern and the remaining 20, although Y-derived, reacted similarly with both male and female DNA.

Chromosomal localization of the human c-fms oncogene

Abstract: A molecular probe was prepared with specificity for the human cellular homologue of transforming sequences represented within the McDonough strain of feline sarcoma virus (v-fms). By analysis of a series of mouse-human somatic cell hybrids containing variable complements of human chromosomes it was possible to assign this human oncogene, designated c-fms, to chromosome 5. Regional localization of c-fms to band q34 on chromosome 5 was accomplished by analysis of Chinese hamster-human cell hybrids containing as their only human components, terminal and interstitial deleted forms of chromosome 5. The localization of c-fms to chromosome 5 (q34) is of interest in view of reports of a specific, apparently interstitial, deletion involving approximately two thirds of the q arm of chromosome 5 in acute myelogenous leukemia cells.

Rat c-myc oncogene is located on chromosome 7 and rearranges in immunocytomas with t(6:7) chromosomal translocation

Abstract: Two B-cell-derived tumours, human Burkitt's lymphoma (BL) and murine plasmacytoma (MPC), are regularly associated with a distinctive form of chromosomal translocation (for reviews see refs 1, 2) In BL, the distal portion of chromosome 8 breaks off and is transposed, in most cases, to chromosome 14, known to carry the immunoglobulin heavy-chain locus In about 5% of the cases the same distal part of the chromosome 8 has moved to either chromosome 2 or 22, to the neighbourhood of the kappa or the lambda locus, respectively In MPC the distal region of chromosome 15 is transposed to the chromosome 12, known to carry the immunoglobulin heavy-chain locus, or enters into reciprocal exchange with the kappa locus-carrying chromosome 6 (ref 7) Several laboratories have located c-myc, the cellular homologue of the MC29 retroviral oncogene v-myc, to human chromosome 8 (refs 8-10) and mouse chromosome 15 (refs 11-13) It has also been shown that the BL- and MPC-associated translocations remove the c-myc gene from its original site and transpose it into or close to one of the immunoglobulin gene clusters In view of the above findings we also looked for possible involvement of the c-myc gene in a B-cell-derived tumour of a third species, the rat Rat immunocytomas of spontaneous origin carry a reciprocal translocation between chromosomes 6 and 7 (ref 17) Here we have localized the c-myc locus to chromosome 7 of the rat Moreover, we have found that the c-myc gene was rearranged in four of five immunocytomas carrying the characteristic chromosomal translocation

[Translocation of chromosome 22 in Ewing's sarcoma].

Abstract: The chromosomal analysis of four fresh Ewing tumours shows a translocation of the band q12 of the chromosome 22 in all the clones observed. This translocation seems to preferentially involve the band q24 of the chromosome 11. These results are in favour of a consistent translocation in Ewing's sarcoma, and are to be compared with the results obtained in other malignancies. A relation between this translocation and the location of the human oncogene c-sis on the chromosome 22 should be considered.

Synthesis of kappa light chains by cell lines containing an 8;22 chromosomal translocation derived from a male homosexual with Burkitt's lymphoma.

Abstract: Three cell lines were derived from a homosexual patient with probable acquired immunodeficiency syndrome and Burkitt's lymphoma. The cell lines produce an unusual strain of Epstein-Barr virus which will both transform cord blood lymphocytes and induce early antigens in Raji cells. Translocations between chromosomes 8 and 22 have occurred in all three lines, but the cells synthesize immunoglobulin M with light chains of the kappa type, in contrast to the usual concordance between a translocation involving chromosome 22 and lambda chain synthesis. Both kappa genes and one lambda gene are rearranged. These findings indicate either that translocation may occur as a separate event from immunoglobulin gene rearrangement or that the proposed hierarchical sequence of immunoglobulin gene rearrangements is not always adhered to. The data also imply that in cells containing a translocation between the long arm of chromosome 8 and a chromosome bearing an immunoglobulin gene, alteration of cellular myc expression may occur regardless of the immunoglobulin gene that is expressed.

A rapid chromosome-mapping method for cloned fragments of yeast dna

Abstract: A rapid and generally applicable method is described for mapping a cloned yeast DNA segment to the chromosome(s) from which it originated. The method is based upon the recent finding that the integration into a yeast chromosome of a segment of the 2μ plasmid DNA results, in heterozygous diploids, in the specific loss of genetic information from the chromosome into which the 2μ DNA was integrated (Falco et al . 1982). After verification of the accuracy of the method using several genes whose position was known in advance, the method was used to locate the yeast actin gene, which lies on the left arm of chromosome VI , about 50 cM distal to CDC4 .

Amplified C lambda and c-abl genes are on the same marker chromosome in K562 leukemia cells

Abstract: The human leukemia cell line K562, derived from a patient with Philadelphia chromosome-positive chronic myelogenous leukemia, contains amplified c-abl oncogenes and unrearranged C lambda genes. Using in situ hybridization techniques, we have determined that the amplified c-abl and C lambda DNA sequences of K562 cells are both located on the same abnormal acrocentric marker chromosome, which may represent an altered Philadelphia chromosome.

Lambda lg constant region genes are translocated to chromosome 8 in Burkitt's lymphoma with t(8:22

Abstract: By in situ hybridization of normal human chromosomes with a cloned genomic probe specific for the constant region of the lambda immunoglobulin genes, band 22q11 was preferentially labelled. In two cell lines with t(8;22) derived from Burkitt's lymphoma a strong signal was noted on the 8q+ chromosome derivative, indicating that the constant region of the lambda Ig gene cluster was translocated from chromosome 22 to chromosome 8. In addition, the signal observed on the 22q- derivative chromosome was stronger than the background in one of the two cell lines tested, but not in the other. The implications are that the break point in chromosome 22 in some cases lies within the Ig gene itself or between clusters of such genes, and that different cases have different break points.

Adult T-cell leukemia. Chromosome analysis of 15 cases.

Abstract: Chromosome studies was conducted on 15 patients with adult T-cell leukemia. Cells with chromosomal abnormality were seen in 14 of the 15 patients. The modal chromosome number was near diploid range in all the patients. The most common abnormality was 14q+ marker chromosome and partial deletion of the long arm of chromosome 6, i.e., 6q-, which were seen in eight and seven cases, respectively. Donor chromosomes involved in the 14q+ marker chromosome varies, i.e., Yq, #5p, #5q, #9q, #10q or #12q, except for two patients whose donor chromosome origins were unable to determine. The break point in 14q+ marker chromosome was band at q32. The 6q- chromosome was due to a deletion in one patient and interstitial deletion in six patients. A 14q- chromosome having break point at q24 was found in one patient and duplication of Yq chromosome in two patients. In addition, four patients showed a 5q- chromosome or a 9q- chromosome which was due to a translocation or deletion. The significance of these chromosome abnormalities was discussed.

Genetic analysis of the 15;17 chromosome translocation associated with acute promyelocytic leukemia.

Abstract: Somatic cell hybrids have been constructed between a thymidine kinase-deficient mouse cell line and blood leukocytes from a patient with acute promyelocytic leukemia showing the 15q+;17q- chromosome translocation frequently associated with this disease. One hybrid contains the 15q+ translocation chromosome and very little other human material. We have shown that the c-fes oncogene, which has been mapped to chromosome 15, is not present in this hybrid and, therefore, probably is translocated to the 17q- chromosome. Analysis of the genetic markers present in this hybrid has enabled a more precise localization of the translocation breakpoints on chromosomes 15 and 17. Our experiments also have enabled an ordering and more precise mapping of several genetic markers on chromosomes 15 and 17.

Direct hybridization of sorted human chromosomes: localization of the Y chromosome on the flow karyotype

Abstract: A method is described for directly hybridizing a small number of sorted chromosomes with specific DNA probes. The chromosomes are analyzed by flow cytometry and sorted by deflecting the droplets containing the desired chromosomes onto a nitrocellulose filter. By using probes specific for the human Y chromosome, it has been possible to unambiguously identify the peak corresponding to the Y chromosome in the flow karyotypes of a variety of male cell lines. The position of this peak was found to vary significantly from individual to individual, correlating with the heterochromatin chromosomal polymorphism of the human Y chromosome. The sensitivity of the hybridization was such that, with a probe for a male-specific repetitive sequence, only 2,500 sorted chromosomes were enough to obtain a clear, positive signal; 10,000 were needed with a probe specific for a weakly repeated (maximum, 3-fold) sequence of Y chromosome. With this new method, chromosome sorting may be a rapid and efficient way to assign DNA sequences to chromosomes.

Sperm chromosome analysis of a man heterozygous for a pericentric inversion of chromosome 3.

Abstract: Using a procedure in which human sperm were allowed to fertilize zona-free golden hamster (Mesocricetus auratus) eggs in vitro, the sperm chromosomes of a man heterozygous for inv(3) (p1 1 q 11) were analyzed. When the chromosomes were Q-banded, the inverted chromosome had the bright centromeric band on the short arm rather than on the long arm, as was seen in the normal No. 3. One hundred and eleven sperm chromosome spreads were examined, of which 64 contained the normal chromosome and 47 the inverted one. This was not significantly different from the expected 1:1 ratio. No sperm containing a chromosome imbalance caused by a crossover within the inversion were seen. Ten (8.1%) of the sperm contained chromosome abnormalities unrelated to the inversion. The ratio of X- to Y-bearing sperm was 55:45.