Showing papers on "Chromosome published in 1983"

Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

Abstract: Inheritance of a mutation at the Rb-1 locus, which has been mapped to band q14 of human chromosome 13, results in predisposition to retinoblastoma. Cloned DNA segments homologous to arbitrary loci of human chromosome 13 and which reveal polymorphic restriction endonuclease recognition sequences, have been used to look for somatic genetic events that might occur during tumorigenesis. A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus. The homozygosity in these cases results from mitotic nondisjunction, resulting in loss of the homologous wild-type chromosome, or from a mitotic recombination event.

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

Translocation of c- abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia

Abstract: The localization of cellular oncogenes near the break points of tumour-specific chromosomal aberrations suggests an involvement of these genes in the generation of neoplasms. Recently, we demonstrated the translocation of the human cellular homologue (c-ab1) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) from chromosome 9 to the Philadelphia chromosome (Ph1) in chronic myelocytic leukaemia (CML). In an attempt to investigate the significance of this translocation in the pathogenesis of CML, we have now studied two CML patients with complex translocations, t(9; 11; 22) and t(1; 9; 22), and two CML Ph1-negative patients with apparently normal karyotypes. In addition to using blot hybridization with human c-ab1 probes and DNA from rodent: CML cell hybrids as before, we have used in situ hybridization of these probes directly to metaphase chromosomes of CML patients. These studies show that the c-ab1 gene is translocated in Ph1-positive but not in Ph1-negative CML patients. CML without the Ph1 chromosome seems to be a distinct entity with a different origin, and this view is supported by clinical observations including correlations which reveal a poorer prognosis.

Translocation and Rearrangements of the c-myc Oncogene Locus in Human Undifferentiated B-Cell Lymphomas

Abstract: The locus for the cellular myc (c-myc) oncogene in humans is located on the region of chromosome 8 that is translocated to chromosome 14 in cells from most undifferentiated B-cell lymphomas. It is shown in this study that the c-myc locus is rearranged in 5 out of 15 cell lines from patients with undifferentiated B-cell lymphomas, and that the rearrangement involves a region at the 5' side of an apparently intact c-myc gene. In at least three patients, this rearranged region appears to contain immunoglobulin heavy chain mu sequences that are located on chromosome 14. The data indicate that this region contains the crossover point between chromosomes 8 and 14. The break point can occur at different positions on both chromosomes among individual cell lines.

Construction of artificial chromosomes in yeast

Abstract: Fifty-five-kilobase long artificial chromosomes containing cloned genes, replicators, centromeres and telomeres have been constructed in yeast. These molecules have many of the properties of natural yeast chromosomes. Centromere function is impaired on short (less than 20 kilobases) artificial chromosomes.

Plasmids, Recombination and Chromosome Mapping in Streptomyces lividans 66

Abstract: SUMMARY: Streptomyces lividans 66 was shown to harbour two self-transmissible plasmids: SLP2, which acts as a sex factor, and SLP3. Derivatives of this strain which had lost both plasmids were used as host strains to study a range of Streptomyces plasmids for their ability to promote their own transfer and to mobilize chromosomal markers. A linkage map of the S. lividans chromosome containing ten markers was derived from the results of matings using several different sex plasmids, and protoplast fusions. SLP2 was transferred interspecifically to S. parvulus ATCC 12434 and to S. coelicolor A3(2); in the latter it acted as a fertility factor. Interspecific crosses also led to the discovery of a further plasmid, SLP4, from S. coelicolor. SLP2, SLP3 and SLP4 could not be visualized on agarose gels using standard plasmid isolation procedures, but their presence was detected by transformation into S. lividans.

Transcriptional activation of the translocated c-myc oncogene in Burkitt lymphoma

Abstract: We have previously demonstrated that translocations of VH genes from chromosome 14 to chromosome 8 and of the c-myc oncogene from chromosome 8 to chromosome 14 occur in Burkitt lymphomas with the t(8;14) chromosome translocation. An association of the c-myc gene with the Cμ immunoglobulin gene has been observed in some but not all Burkitt lymphomas studied previously. In the present study, we have investigated the organization of the human heavy chain locus and of the c-myc gene in the P3HR-1 Burkitt lymphoma cell line. Becuase mouse/P3HR-1 somatic cell hybrids that retain only the 14q+ chromosome and no other human chromosome contain the human Cμ and Cγ genes but not VH genes, we have concluded that the breakpoint on chromosome 14 in P3HR-1 cells is distal to Cμ and between Cμ and VH. Thus, the breakpoint of human chromosome 14 differs in different Burkitt lymphoma cell lines. We also found that the human c-myc oncogene translocated to chromosome 14 in the P3HR-1 cell line is not recombined with the Cμ gene. The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because we have observed DNA rearrangement of the c-myc gene with the Cμ gene in only some of the Burkitt lymphoma cell lines studied elsewhere. Interestingly, high levels of transcripts of the c-myc oncogene were observed in Burkitt lymphomas with translocated c-myc oncogenes both rearranged and unrearranged. Therefore, the translocation of a c-myc oncogene to the heavy chain locus on human chromosome 14 is apparently sufficient for its transcriptional activation and may be an essential step in the pathway leading to neoplasia.

High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization

Abstract: The method of in situ hybridization has become a significant technique for specific-site chromosome mapping. We show that the resolution of in situ hybridization can be increased by hybridizing the probe to stretched prometaphase chromosomes with high-resolution banding obtained after 5-bromodeoxyuridine treatment of the cells and with a Hoechst 33258/Giemsa chromosome-staining method. Using this procedure, we assigned to specific chromosome sites three cloned genes and one DNA polymorphism: amylase gene (AMY) to 1p21; proopiomelanocortin gene (POMC) to 2p23, somatostatin gene (SST) to 3q28, and a single copy DNA segment (D3S1) to 3q12.

Growth of chromosome ends in multiplying trypanosomes

Abstract: Some of the genes for the variant surface glycoproteins of trypanosomes are located close to a discontinuity in the DNA, presumably a chromosome end We show here that DNA fragments containing these telomeres increase in length in multiplying trypanosomes at a rate of about 10 base pairs per division We argue that chromosome growth may not be restricted to trypanosomes and could explain the heterogeneity of telomeric DNA fragments observed in some other organisms

Translocations and modifications of chromosomes in triticale × wheat hybrids.

Abstract: Several generations of four triticale × wheat populations were cytologically analyzed on a plant-by-plant basis using C-banding. Among 785 karyotyped plants, 195 wheat/rye and 64 rye/rye translocated chromosomes were found, as well as 15 rye chromosomes that were modified by deletion or amplification of telomeric heterochromatin. Most of the translocations involved complete chromosome arms; only a few involved smaller segments of chromosomes. Out of 39 identified wheat/rye translocations, 10 occurred between homoeologous and 29 between non-homoelogous chromosomes, five involved A-genome chromosomes, six B-genome chromosomes and the remaining 28 involved D-genome chromosomes. The study indicated that wheat/rye translocations can be produced in sufficient numbers to allow the use of this method for the introduction of alien variation into wheat research programs. Changes in the C-banding technique used are discussed in detail.

Aneuploidy induction and cell transformation by diethylstilbestrol: a possible chromosomal mechanism in carcinogenesis.

Abstract: Diethylstilbestrol (DES) has been demonstrated previously to induce morphological and neoplastic transformation of Syrian hamster embryo cells in the absence of any measurable induction of gene mutation. To determine if DES induces cell transformation by a genetic mechanism at the chromosomal level, the effect of DES on structural aberrations and numerical chromosome changes was examined in asynchronous and synchronized cells. Over the concentration range which is optimal for cell transformation, DES failed to induce any increase in chromosome aberrations in the cells. In contrast, significant numerical chromosome changes were observed in DES-treated cultures. The percentage of metaphases with a near diploid chromosome number increased to 19% at 48 hr after treatment. By comparison, cells from control cultures contained only 1 to 2% aneuploid metaphases with a near diploid chromosome number. No significant increase in the number of metaphases with a near tetraploid number (>70) of chromosomes was observed in the DES-treated cultures. DES induced both chromosome loss and gain, and no significant difference was detected between the number of hyperdiploid and hypodiploid cells. Chromosome loss or gain was observed for chromosomes in each karyotype group. These findings suggest that DES induces chromosome nondisjunction. Synchronized cell cultures were obtained by first growing the cells in 1% serum and then in 10% serum with hydroxyurea which blocked the cells at the G1-S border. Upon release of the hydroxyurea block, the cells entered into S phase in a very synchronous manner. The cells were treated for 3 hr during one of four time periods after hydroxyurea release. During the first period, the cells were primarily in early S phase, while the second period included cells in late S phase. During the third period most of the cells were undergoing mitosis, while in the fourth period most of the cells were in G1 phase, although some mitotic cells were observed. Treatment of the synchronized cells with DES during early or late S phase resulted in little morphological transformation. However, treatment during the third period, when the majority of the cells were in mitosis, resulted in a peak of transformation which was 15 times the level observed in cultures treated in early or late S phase. Treatment during the fourth time period resulted in a reduced level of cell transformation. Treatment of synchronized cultures with DES resulted also in a cell cycle-dependent induction of aneuploid cells which paralleled the induction of cell transformation, with the greatest level observed following treatment during mitosis. No increase in the percentage of polyploid metaphases or chromosome aberrations was observed in the DES-treated synchronized cells. Parallel dose-response curves for cell transformation and aneuploidy induction by DES were observed when the synchronized cultures were treated during the mitotic phase of the cell cycle. Possible mechanisms for DES-induced aneuploidy and the evidence supporting a role for nonrandom numerical chromosome changes in neoplastic development, as well as significance of aneuploidy in cancer, are discussed.

Chromosomal Differences Among Rainbow Trout Populations

Abstract: Most males showed a morphological difference between the X and Y chromosomes but a number of males with no apparent sex chromosome heteromorphism were observed. These fish were particularly common in some populations; these may represent areas in which the rearrangement resulting in a morphological difference between the X and Y has not become fixed in the population.

The location of the photoperiod gene, Ppd2 and an additional genetic factor for ear-emergence time on chromosome 2B of wheat

Abstract: The location of the photoperiod gene, Ppd 2 and an additional genetic factor for ear-emergence time on chromosome 2B of wheat

Translocation of an immunoglobulin kappa locus to a region 3' of an unrearranged c-myc oncogene enhances c-myc transcription.

Abstract: We have studied somatic cell hybrids between mouse myeloma and JI Burkitt lymphoma cells carrying a t(2;8) chromosome translocation for the expression of human kappa chains. and for the presence and rearrangements of the human c-myc oncogene and kappa chain genes. Our results indicate that the c-myc oncogene is unrearranged and remains on the 8q+ chromosome of JI cells. Two rearranged C kappa genes were detected: the expressed allele on normal chromosome 2 and the excluded kappa allele that was translocated from chromosome 2 to the involved chromosome 8 (8q+). The distribution of V kappa and C kappa genes in hybrid clones retaining different human chromosomes indicated that C kappa is distal to V kappa on 2p and that the breakpoint in this Burkitt lymphoma is within the region carrying V kappa genes. High levels of transcripts of the c-myc gene were found when it resided on the 8q+ chromosome but not on the normal chromosome 8, demonstrating that translocation of a kappa locus to region distal to the c-myc oncogene enhances c-myc transcription.

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.

Association of amplified oncogene c- myc with an abnormally banded chromosome 8 in a human leukaemia cell line

Abstract: Several unusual chromosome structures have been described in drug-resistant cell lines and in certain tumours. These structures include elongated homogeneously staining regions (HSRs), small extrachromosomal paired chromatin bodies (double minutes, DMs) and abnormally banded regions (ABRs) with strong but anomalous band patterns1–3. There is evidence that these are alternative forms of gene amplification, with HSRs breaking down to form DMs, and DMs integrating into the chromosome to generate HSRs and ABRs5–7. Recently, it was demonstrated that, compared with several normal leukaemia human cells, DNA sequences representing the human homologue of the onc gene of the avian myelocytomatosis virus (MC29), the so-called c-myc gene, were amplified in HL-60 cells11,12. This is a human pro-myelocytic leukaemia cell line established in the laboratory of one of us (R.C.G.) at the National Cancer Institute (Bethesda, Maryland) in 1977, and widely used for studies on myeloid and monocytic differentiation8–10. Amplification of the gene was present in primary leukaemic cells of the patient12, and DMs were noted in some of these cells as well as in early passages of the HL-60 line13. No structure resembling HSRs or ABRs were noted in karyotypic studies at this early stage13 and there were no alterations involving the long arm of chromosome 8 (8q), to which the c-myc gene has recently been mapped14–16. We have now re-examined the karyotype of the HL-60 line, using cells frozen at various times during its continuous passage at the Wistar Institute (Philadelphia, Pennysylvania) to look for chromosomal abnormalities that might be associated with the amplification of c-myc. We find that, beginning in 1979, HL-60 cells at the Wistar Institute no longer had DMs, but did show an abnormal 8q+ chromosome, replacing a normal chromosome 8, and representing an ABR reflecting the site of myc gene amplification.

Multigene family for sarcomeric myosin heavy chain in mouse and human DNA: localization on a single chromosome

Abstract: Cloned myosin heavy chain DNA probes from rat and human were hybridized to restriction endonuclease digests of genomic DNA from somatic cell hybrids and their parental cells. The mouse myosin heavy chain genes detectable by this assay were located on chromosome 11, and three different human sarcomeric myosin heavy chain genes were mapped to the short arm of chromosome 17. A synteny between myosin heavy chain and two unrelated markers, thymidine kinase and galactokinase, was found to be preserved in the rodent and human genomes.

Cytogenetic studies on an epithelial cell line derived from poorly differentiated nasopharyngeal carcinoma

Abstract: An epithelial cell line, CNE-2, has been recently established from a poorly differentiated nasopharyngeal carcinoma, and it represents the first of its kind. Using chromosome banding techniques, cytogenetic analysis of the cell line was carried out. It was demonstrated that the chromosome numbers of the CNE-2 cells varied from 87 to 107 and the modal number was 104-103. All cells contained a series of structurally abnormal chromosomes, and most of them were either consistent or frequently found. Among these chromosomes there were two giant markers which, by banding pattern analysis, proved to be distinct from the so-called giant group A marker chromosomes previously found in many lymphoblastoid cell lines from NPC. Comparison between the CNE-2 and CNE, another epithelial cell line, which was established from well-differentiated squamous NPC, showed that while they were quite different in many cytogenetic aspects, they had three marker chromosomes in common, namely, an iso8q, a t(?;3q) and a small acrocentric one. The question of whether chromosome markers specific for NPC exist is discussed in the light of the data presented.

Spontaneous Neoplastic Evolution of Chinese Hamster Cells in Culture: Multistep Progression of Karyotype

Abstract: Chromosomes from successive passages of a Chinese hamster cell strain (WCHE/5) that spontaneously progressed from a euploid primary cell culture to a heteroploid tumorigenic cell line were isolated and analyzed by Giemsa banding and high-resolution flow karyotype analysis. The frequency and identification of aneuploid and marker chromosomes were determined at both pre- and postcrisis culture stages and pre- and posttumorigenic stages. The combination of Giemsa banding and flow karyotypes provided detailed analysis of karyotype instability at each stage of cell culture progression. Aneuploidy (trisomy of chromosome 5) preceded the appearance of tumorigenicity in nude mice as well as in vitro indicators of neoplasia. The four stages of neoplastic progression defined in the previous paper correlated with a steady progression in karyotypic instability, including, in sequence: trisomy of chromosome 5; an 8q marker chromosome; a 3q+ insertion; and trisomy of chromosome 8. Additional changes continued to appear as the cells acquired classical properties of in vitro transformation.

Chromosome assignment of genes encoding the alpha and beta subunits of glycoprotein hormones in man and mouse.

Abstract: The chromosomal locations of the genes for the common alpha subunit of the glycoprotein hormones and the beta subunit of chorionic gonadotropin in humans and mice have been determined by restriction enzyme analysis of DNA isolated from somatic cell hybrids. The CG alpha gene (CGA), detected as a 15-kb BamHI fragment in human DNA by hybridization to CG alpha cDNA, segregated with the chromosome 6 enzyme markers ME1 (malic enzyme, soluble) and SOD2 (superoxide dismutase, mitchondrial) and an intact chromosome 6 in human-rodent hybrids. Cell hybrids containing portions of chromosome 6 allowed the localization of CGA to the q12 leads to q21 region. The greater than 30- and 6.5-kb BamHI CGB fragments hybridizing to human CG beta cDNA segregated concordantly with the human chromosome 19 marker enzymes PEPD (peptidase D) and GPI (glucose phosphate isomerase) and a normal chromosome 19 in karyotyped hybrids. A KpnI-HindIII digest of cell hybrid DNAs indicated that the multiple copies of the CG beta gene are all located on human chromosome 19. In the mouse, the alpha subunit gene, detected by a mouse thyrotropin (TSH) alpha subunit probe, and the CG beta-like sequences (CG beta-LH beta), detected by the human CG beta cDNA probe, are on chromosomes 4 and 7, respectively.

DNA variation between and within chromosome complements of vicia species

Abstract: 2C nuclear DNA amounts in diploid species of the genus Vicia (x = 5, 6, and 7) range from approximately four to twenty seven picograms. The DNA amount varies independently of the chromosome number and of taxonomic grouping within the genus. Comparisons of the distribution of DNA amounts among chromosomes within the complements show that increase in total nuclear DNA amount within the genus is achieved by equal increments to each chromosome independent of size i.e., small chromosomes acquire the same amount of extra DNA as the large chromosomes. An inevitable consequence of such a pattern of DNA change is that the chromosomes within complements with high DNA amount are more alike in size and DNA content, more symmetrical, than within complements of species with low DNA amount. In a few species the symmetry is confounded as a result of Robertsonian fusion. The equal distribution of extra DNA among chromosomes within a complement has been reported in other genera of flowering plants viz. in Lolium, Festuca and Lathyrus. In all cases there is evidently a severe constraint either upon the way in which the nuclear DNA variation is achieved or else upon its persistence in the face of selection. Since the pattern of change affects the relative sizes of chromosomes within complements we conclude that relative size may itself be of adaptive importance.

Genomic substitutions of centromeres in Saccharomyces cerevisiae

Abstract: The centromere region of yeast chromosome III has been investigated by altering it in vivo. Deleting the functional centromere (CEN3) sequence leads to extreme instability of the resulting acentric chromosome. Inversion of CEN3, or its replacement by chromosome XI centromere DNA (CEN11) has no measurable effect on the mitotic and meiotic behaviour of chromosome III, suggesting that yeast centromeres are not chromosome-specific, and are fully functional in either orientation.

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.

Chromosomal Aberrations Observed in 52 Mouse Myeloid Leukemias

Abstract: Chromosomes of 52 cases of mouse myeloid leukemia were examined. There were 5 myeloblastic leukemias, 22 granulocytic leukemias, 17 myelomonocytic leukemias, and 8 monocytic leukemias. Fifty cases were radiation induced and the other 2 were nonirradiated. Each case had leukemic cells with 1 to 10 marker chromosomes. Partially deleted No. 2 chromosomes appeared in 49 cases, including 2 nonirradiated cases. These deleted No. 2 chromosomes were varied in size, and they were classified into 7 types according to morphological features. There was no type-dependent difference in histological or cytological features among the 7 types. It was found that the chromosomal segment lying between Regions 2C and 2D was commonly missing from all of the deleted No. 2 chromosomes. In addition to such No. 2 chromosomes, an anomaly in chromosome 6 was observed in 16 cases, of which 12 cases were granulocytic leukemia. The abnormalities of chromosomes 3 and 9 were next most frequent, appearing in 14 cases each. Besides such structural anomalies, numerical changes involving the Y chromosome (33 cases), chromosome 6 (6 cases), and chromosome 15 (4 cases) were also found. Characteristics of the karyotypes of the mouse myeloid leukemia in comparison with other leukemias were noted. The significance of the specific segments of the chromosomes which were commonly missing or trisomic in the karyotypes of neoplasias in mice, rats and humans was discussed. It was suggested that the genesis of myeloid leukemia was greatly influenced by the genetic information on chromosome 2 in mice.

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.

Identification of reciprocal translocation sites within the c-myc oncogene and immunoglobulin mu locus in a Burkitt lymphoma.

Abstract: The association between certain human tumours and characteristic chromosomal abnormalities has led to the hypothesis that specific cellular oncogenes may be involved and consequently 'activated' in these genetic recombinations. This hypothesis has found strong support in the recent findings that some cellular homologues of retroviral onc genes are located in chromosomal segments which are affected by specific tumour-related abnormalities (see ref. 4 for review). In the case of human undifferentiated B-cell lymphoma (UBL) and mouse plasmacytomas, cytogenetic and chromosomal mapping data have identified characteristic chromosomal recombinations directly involving different immunoglobulin genes and the c-myc oncogene (for review see refs 5, 6). In UBLs carrying the t(8:14) translocation it has been shown that the human c-myc gene is located on the region of chromosome 8 (8q24) which is translocated to the immunoglobulin heavy-chain locus (IHC) on chromosome 14. Although it is known that the chromosomal breakpoints can be variably located within or outside the c-myc locus and within the IHC mu (refs 9, 11) or IHC gamma locus, the recombination sites have not been exactly identified and mapped in relation to the functional domains of these loci. We report here the identification and characterization of two reciprocal recombination sites between c-myc and IHC mu in a Burkitt lymphoma. Nucleotide sequencing of the cross-over point joining chromosomes 8 and 14 on chromosome 14q--shows that the onc gene is interrupted within its first intron and joined to the heavy-chain mu switch region. This recombination predicts that the translocated onc gene would code for a rearranged mRNA but a normal c-myc polypeptide.

A direct demonstration of somatically paired heterochromatin of human chromosomes.

Abstract: Human lymphocyte cultures were treated with different concentrations of 5-azacytidine for various lengths of time. This cytosine analog induces very distinct undercondensation in the heterochromatin o

Gene amplification in yeast: CUP1 copy number regulates copper resistance

Abstract: The CUP1 locus in yeast confers resistance to copper toxicity. We determined the molecular basis for copper resistance in three yeast strains, with differing degrees of resistance. Increased resistance to copper is associated with overproduction of a low molecular weight copper-binding protein, copper-chelatin. Increased chelatin synthesis results from amplification of the CUP1(r) gene and increased synthesis of the copper inducible mRNA. The copper resistance level of a given strain correlates directly with the gene copy number.Strains containing one copy and ten tandemly iterated copies of the CUP1 gene were studied. From the latter, a haploid strain with enhanced resistance was isolated following several selection cycles at elevated copper concentrations. This strain was disomic for chromosome VIII, the chromosome containing the CUP1 locus. The disomic chromosomes exhibit differential CUP1 gene amplification: 11 and 14 tandemly organized repeat units are found in the respective chromosome VIII homologues. We propose that the molecular mechanisms of gene amplification involve unequal sister chromatid exchange and intrachromosomal gene conversion, as well as disomy.