Showing papers on "Chromosome 22 published in 1984"

Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation

Abstract: From an acute B-cell leukemia cell line, a DNA probe was obtained that was specific for chromosome 18 and flanked the heavy chain joining region of the immunoglobulin heavy chain locus on chromosome 14. This probe detected rearrangement of the homologous DNA segment in the leukemic cells and in follicular lymphoma cells with the t(14:18) chromosome translocation but not in other neoplastic or normal B or T cells. The probe appears to identify bcl-2, a gene locus on chromosome 18 (band q21) that is unrelated to known oncogenes and may be important in the pathogenesis of B-cell neoplasms with this translocation.

T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria.

Abstract: Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein-Barr virus (EBV), is common in areas of Africa where malaria is holoendemic. The tumour is characterized by chromosome translocations; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 14, near the enhancer of the immunoglobulin heavy-chain locus. Less frequent are translocations of chromosome 8 to the kappa light-chain locus of chromosome 2 or to the lambda light-chain locus of chromosome 22. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients. Such patients are subsequently liable to develop lymphomas. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a "reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites". We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common.

High-Resolution Chromosome Sorting and DNA Spot-Blot Analysis Assign McArdle's Syndrome to Chromosome 11

Abstract: A rapid gene-mapping system uses a high-resolution, dual-laser sorter to identify genes from separate human chromosomes prepared with a new stain combination. This system was used to sort 21 unique chromosome types onto nitrocellulose filter papers. Several labeled gene probes hybridized to the sorted chromosomal DNA types predicted by their previous chromosome assignments. The skeletal muscle glycogen phosphorylase gene was then mapped to a portion of chromosome 11 by spot blotting normal and translocated chromosomes.

An 8-kilobase abl RNA transcript in chronic myelogenous leukemia.

Abstract: Chronic myelogenous leukemia (CML) is a clonal hematologic malignancy characterized by a reciprocal translocation between chromosomes 9 and 22 [t(9;22)] in greater than 90% of cases. This translocation results in a short chromosome 22, termed the Philadelphia (Ph1 or 22q-) chromosome. Recently, the cellular oncogenes abl and sis were mapped to human chromosomes 9 and 22, respectively. Moreover, abl was shown to be translocated from chromosome 9 to 22 and sis from chromosome 22 to 9 in CML patients with t(9;22). These findings raised the possibility that one or both of these oncogenes is activated and directly involved in the development of the disease. We analyzed expression of the abl and sis oncogenes in leukemic cells from CML patients with t(9;22). We found that sis is not expressed but that abl is transcribed into an 8-kilobase RNA. This abl RNA is also present in two leukemic cell lines (EM2 and K562), which were derived from CML patients and contain the t(9;22). This 8-kilobase RNA is not detected in normal cells, in other human leukemias without t(9;22), or in human cell lines that lack t(9;22). The consistent presence of this abl RNA transcript in CML with t(9;22) suggests that it is a consequence of abl translocation and that it plays a role in the development of this leukemia.

Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13.

Abstract: A recombinant DNA library enriched for portions of human chromosome 13 has been constructed from a hamster-human somatic cell hybrid that contained human chromosomes 13, 12, and 6p. A total of 733 phages were identified that contain human DNA inserts, and 46 single-copy subfragments have been derived and used as probes on Southern transfers of genomic DNA isolated from unrelated individuals. From this set, nine fragments revealing polymorphic loci (RFLP) in Msp I- or Taq I-digested DNA have been identified, of which three are polymorphic with both enzymes. Six of these probes have been shown to segregate concordantly with human chromosome 13 in a somatic cell hybrid mapping panel, and the RFLPs at these loci have been shown to behave as codominant Mendelian alleles. Additionally, hybridization to DNA isolated from cells containing various deletions of chromosome 13 has allowed regional localization. This recombinant DNA library will be useful in the study of retinoblastoma as well as in the study of the mechanisms responsible for abnormalities of this autosome.

Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.

Abstract: Using a human X chromosome-specific DNA library, we have found arbitrary single-copy DNA sequences that reveal useful restriction fragment length polymorphisms. The inheritance of these and other available polymorphic DNA markers has been studied in a series of unrelated three-generation families with large sibships. These families reveal parental phase and allow determination of recombination frequencies by counting recombinant and nonrecombinant chromosomes. The resulting genetic map indicates that the minimal distance from Xp22 to Xqter is 215 recombination units. The spacing of the marker loci is such that the majority of the loci on the X chromosome, including disease loci, will lie within 20 centimorgans of at least one of these loci.

Chromosomal and nuclear distribution of the HindIII 1.9-kb human DNA repeat segment

Abstract: A human interspersed repetitive DNA cloned in pBR322, the HindIII 1.9-kb (kilobase pair) sequence, was labeled with biotinylated dUTP and hybridized to acid-fixed chromosomes and paraformaldehyde-fixed whole cells in situ. Using our most sensitive detection techniques this probe highlighted on the order of 200 discrete loci, in punctate or banded arrays, that resembled a Giemsa-dark band pattern on chromosome arms. Interphase cells also displayed many discrete punctate spots of hybridization along chromosome fibers. The ubiquitous Alu sequence repeat also appeared to be concentrated in specific regions of the chromosome and predominantly highlighted Giemsa-light bands. Centromeric or ribosomal spacer DNA repeats used as controls in all studies gave the expected hybridization profiles and showed no non-specific labeling of chromosome arms. Cohesive groups of centromeric DNA arrays and rDNA clusters were observed in interphase nuclei. Refinements in methods for detecting biotin-labeled probes in situ were developed during these studies and calculations indicated that about 20 kb or more of the 1.9-kb repeat were present at each hybridization site. The chromosomal distribution of the 1.9-kb repeat suggests that this sequence may reflect, or participate in defining, ordered structureal domains along the chromosome.

Characterization of a cloned DNA sequence that is present at centromeres of all human autosomes and the X chromosome and shows polymorphic variation

Abstract: We have identified a human DNA recombinant (p308) with a 3.0-kilobase (kb) BamHI insert that hybridizes in situ exclusively to the centromeric region of all human autosomes and the X chromosome. This highly repetitive sequence is significantly enriched on several chromosomes, most prominently on chromosome 6. In all individuals, the majority of genomic repeats are organized as tandem 3.0-kb BamHI repeats, each containing one Taq I site; the others are organized into BamHI and Taq I repeats of variable size that have some chromosome specificity. Using mouse-human hybrids, we have defined the specific organization of this sequence on chromosomes 6, 3, and X. In some individuals, there are differences in the number and nature of the tandem repeats. These polymorphisms segregate in families as if chromosome specific. Although variable from one chromosome to another, 308 contains sequences homologous to DNA present in centric heterochromatin of essentially all human chromosomes and is evolutionarily conserved. Therefore, a significant component of pericentric DNA is similar for all human chromosomes.

Meiotic and mitotic behavior of dicentric chromosomes in saccharomyces cerevisiae

Abstract: Meiotic recombination between a circular and a linear chromosome in Saccharomyces cerevisiae has been investigated. The circle was a haploid-viable derivative of chromosome III constructed by joining regions near the two chromosome ends via a recombinant DNA construction: (HMR/MAT-URA3-pBR322-MAT/HML) and was also deleted for MAL2 (which therefore uniquely marks a linear chromosome III). Recombination along chromosome III was measured for eight intervals spanning the entire length of the circular derivative. Only 25% of all tetrads from a ring/rod diploid contained four viable spores. These proved to be cases in which there was either no recombination along chromosome III or in which there were two-strand double crossovers or higher order crossovers that would not produce a dicentric chromosome.--At least half of the tetrads with three viable spores included one Ura+ Mal+ spore that was genetically highly unstable. The Ura+ Mal+ spore colonies gave rise to as many as seven genetically distinct, stable ("healed") derivatives, some of which had lost either URA3 or MAL2. Analysis of markers on chromosome III suggests that dicentric chromosomes frequently do not break during meiosis but are inherited intact into a haploid spore. In mitosis, however, the dicentric chromosome is frequently broken, giving rise to a variety of genetically distinct derivatives. We have also shown that dicentric ring chromosomes exhibit similar behavior: at least half the time they are not broken during meiosis but are broken and healed during mitosis.--The ring/rod diploid can also be used to determine the frequency of sister chromatid exchange (SCE) along an entire yeast ring chromosome. We estimate that an unequal number of SCE events occurs in approximately 15% of all cells undergoing meiosis. In contrast, the mitotic instability (and presumably SCE events) of a ring chromosome is low, occurring at a rate of about 1.2 X 10(-3) per cell division.

A variant translocation places the λ immunoglobulin genes 3′ to the c- myc oncogene in Burkitt's lymphoma

Abstract: Most translocations that occur in Burkitt's lymphoma1,2 involve movement of part of chromosome 8, containing the c-myc gene, from its normal position to the immunoglobulin heavy-chain locus on chromosome 143–7. The genes are often joined at their 5′ ends in opposite transcriptional directions4–13. However, a significant minority of Burkitt translocations8 involve the light-chain loci on chromosome 2 (κ)14 or 22 (λ)15. We have characterized one of these from a European-derived cell line (IARC-BL37) that carries an 8;22 translocation. Here the translocation has joined the 5′ portion of the λ light-chain locus to the 3′ portion of the c-myc gene at a position about 7 kilobases from the normal c-myc promoters. The translocation is reciprocal and relatively conservative, involving the loss of only 21 base pairs from the site of recombination. This translocation allows us to orient the λ genes with respect to the centromere of chromosome 22 and to predict the orientation of other translocations involving these chromosomal segments. The 3′ translocation is accompanied by an increased level of c-myc transcripts, especially that derived from a normally under-used c-myc promoter.

5-Azacytidine-induced undercondensations in human chromosomes

Abstract: The cytosine analogue 5-azacytidine induces very distinct undercondensations in human chromosomes if applied to lymphocyte cultures. The number of induced undercondensations and their chromosomal localization can be varied by the 5-azacytidine dose and the treatment time. “Pulverized” chromosomes or undercondensations in the G-band-positive chromosome regions are produced with high doses and long treatment times. If applied in low doses during the last hours of culture, 5-azacytidine induces specific undercondensations in the heterochromatin of chromosomes 1, 9, 15, 16, and Y. Optimum conditions required for inducing the various types of undercondensation in the chromosomes were determined. Various examples of the use 5-azacytidine in the analysis of chromosome rearrangements involving heterochromatic regions are presented.

Genes for serum amyloid A proteins map to Chromosome 7 in the mouse.

Abstract: Several restriction fragment length variants have been detected among inbred strains using a mouse serum amyloid A cDNA clone. Five variants were shown to segregate as a single genetic unit and were mapped to Chromosome 7 between the glucose phosphate isomerase locus (Gpi-1) and the pink eye dilution locus (p) using recombinant inbred and congenic strains. The finding that no major MspI or BclI restriction fragments were shared between digests of DNAs from a Chromosome 7 congenic strain and its inbred partner, indicate that most, and probably all, sequences detected with the probe are clustered on Chromosome 7. Aneuploid mapping was used to show that the serum amyloid A gene complex (Saa) is proximal to the Chromosome 7 breakpoint in T(7;X)1Ct, a translocation in which the middle third of Chromosome 7 is inserted into the X-chromosome. A survey of inbred strains revealed a single common Saa haplotype and eight rare haplotypes. The complex distribution of 14 different variants suggests that recombination may have played a role in haplotype evolution.

A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia

Abstract: A human cDNA library was screened for sequences homologous to the erbA gene of avian erythroblastosis virus (AEV). One such clone, cHerbA-1, was used to map the chromosomal location of highly homologous human sequences that were found to be present on chromosome 17 as judged by Southern blot screening of a panel of mouse-human hybrid cell lines segregating human chromosomes. cHerbA-1 was hybridized in situ to metaphase chromosomes from a normal male subject and from a female patient with an acute promyelocytic leukemia (APL) having the typical t(15;17) translocation. The results localized the cellular c-erbA sequences on chromosome 17 to the q21-q24 region of normal chromosomes and indicated that the c-erbA sequences remained on the 17q- chromosome in the APL cells, suggesting that they could be assigned to the 17(q21-q22) region. For additional data, we hybridized human neoplastic cells derived from a poorly differentiated acute leukemia carrying a t(17;21) translocation with thymidine kinase (TK)-deficient LMTK- mouse cells. A resulting hybrid, containing only the 21q+ chromosome, did not have human c-erbA sequences. Since the breakpoint on 17q in this translocation was similar to that in the APL t(15;17) translocation, this supported the assignment of c-erbA to the q21-q22 region of chromosome 17. The apparent close proximity of the c-erbA sequences to the chromosomal breakpoints in these two leukemias suggests a possible role for this oncogene homologue in the development of these neoplasms.

Organization of the HPRT gene and related sequences in the human genome

Abstract: Comparative Southern hybridization of cDNA probes to DNA from cells carrying either one or four X chromosomes has been used to distinguish sequences derived from the functional locus for hypoxanthine-guanine phosphoribosyltransferase (HPRT) on the X chromosome from four independent HPRT-like autosomal sequences in the human genome. Subfragments of cDNA were then used to orient fragments from the HPRTlocus with respect to the mRNA sequence. The chromosomal origin of each of the autosomal sequences was determined by Southern analysis using DNA from a panel of human-Chinese hamster somatic cell hybrids. Two of the HPRT-like sequences were localized to chromosome 11, the third to chromosome 3, and the fourth to the region between p13 and q11 on chromosome 5. Three of these four autosomal sequences were isolated from genomic recombinant libraries and subcloned fragments from each were used as probes to study restriction fragment length polymorphisms (RFLP) at these loci. A RFLP for MspIwas found at the HPRT-like locus on chromosome 5 with a 1.3-kb major allele (frequency=0.8) and a 3.6-kb minor allele (frequency=0.2).

Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis.

Abstract: The behaviour of chromosome 15 is very different from that of the other acrocentric chromosomes. The cytogenetic characteristics of rearrangements associated with Prader-Willi syndrome (PWS) are analyzed as similar rearrangements irrespective of the associated phenotype (reciprocal translocations of chromosome 15, small bisatellited additional chromosomes, Robertsonian translocations, interstitial deletions, pericentric inversions). This study suggests that: (1) The proximal (15q) region and PWS seem to be indissociable; (2) chromosome 15 has an indisputable cytogenetic originality which could be related to its histochemical properties. Chromosome 15 constitutive heterochromatin usually contains much 5-methylcytosine-rich DNA and a large amount of each of the four satellite DNAs. Furthermore the existence in the proximal (15q) region of one or several palindromic sequences could be postulated to explain the great lability of this region of chromosome 15.

Familial DiGeorge syndrome and associated partial monosomy of chromosome 22

Abstract: Partial monosomy of 22q due to an unbalanced 4;22 translocation was seen in a 2-month-old male with Type I truncus arteriosus, dysmorphic features, and T-cell abnormalities The family history revealed a previous sib with Type I truncus arteriosus, thymic aplasia, and parathyroid hypoplasia noted on postmortem examination, consistent with DiGeorge syndrome Evaluation of the asymptomatic mother of these two patients revealed partial T-cell deficiency and the same unbalanced translocation with deletion of proximal 22q11 These findings provide further evidence that some cases of complete or partial DiGeorge syndrome are associated with monosomy of the proximal long arm of chromosome 22, and they may explain many, if not all, familial cases of the syndrome

The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus

Abstract: We hybridized neoplastic cells from a patient with chromic lymphocytic leukemia of the B-cell type, which carried a reciprocal chromosomal translocation between chromosomes 11 (q13) and 14 (q32) with mouse plasmacytoma cells. The hybrid cells were studied for the presence, rearrangement, and expression of the human immunoglobulin mu chain locus. The results indicate that the expressed mu chain gene is located on the normal chromosome 14, whereas the 14q+ translocation chromosome carries the excluded immunoglobulin constant (C) region mu chain allele (C mu) but does not contain variable (V) region heavy chain genes (VH). Since we found that the heavy chain joining region DNA (JH) of the excluded mu chain gene is on the 14q+ chromosome, we can conclude that the chromosomal break observed in the leukemic cells occurred in a chromosomal region within or 5' of the JH region. With these results, it is logical to postulate that a gene, for which we suggest the name bcl-1, is located on band q13 of chromosome 11 and is activated by its translocation into close proximity with the rearranged heavy chain locus on chromosome 14q+, contributing to the neoplastic transformation of the B cells with the t(11;14) chromosomal translocation.

Gene for T-cell growth factor: location on human chromosome 4q and feline chromosome B1

Abstract: T-cell growth factor (TCGF) or interleukin-2 (IL-2), an immunoregulatory lymphokine, is produced by lectin- or antigen-activated mature T lymphocytes and in a constitutive manner by certain T-cell lymphoma cell lines. By means of a molecular clone of human TCGF and DNA extracted from a panel of somatic cell hybrids (rodent cells X normal human lymphocytes), the TCGF structural gene was identified on human chromosome 4. In situ hybridization of the TCGF clone to human chromosomes resulted in significant labeling of the midportion of the long arm of chromosome 4, indicating that the TCGF gene was located at band q26-28. Genomic DNA from a panel of hybrids prepared with HUT-102 B2 cells was examined with the same molecular clone. In this clone of cells, which produces human T-cell leukemia virus, the TCGF gene was also located on chromosome 4 and was apparently not rearranged. The homologous TCGF locus in the domestic cat was assigned to chromosome B1 by using a somatic cell hybrid panel that segregates cat chromosomes. Linkage studies as well as high-resolution G-trypsin banding indicate that this feline chromosome is partially homologous to human chromosome 4.

Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma cells.

Abstract: In Burkitt lymphoma cells reciprocal chromosomal translocations are observed between the long arm of chromosome 8 (8q24) and either the long arm of chromosome 14 (14q32), the short arm of chromosome 2 (2p12) or the long arm of chromosome 22 (22q11). Gene mapping studies have shown that c-myc, the cellular homologue of the viral myc oncogene, is localized at 8q24 (ref 3-5) and that the three immunoglobulin gene loci map at the breakpoints involved in the translocation: immunoglobulin heavy-chain genes are located at 14q32 (refs 6, 7), kappa light chains at 2p12 (ref. 8) and delta light chains at, or close to, 22q11 (ref 9, 10). This correlation suggests an association of immunoglobulin gene rearrangements with the occurrence of these specific translocations. By using in situ hybridization we have examined the translocation point with respect to c-myc in two cell lines containing 2;8 translocation, and report here that the c-myc gene remains on the chromosome 8 involved in the reciprocal exchange with chromosome 2. We have also confirmed that the c-myc gene moves from the translocated chromosome 8 in a cell line having a 8;14 translocation. These results show that chromosomal breakage can occur on either side of the c-myc gene in Burkitt lymphoma cells.

The DNA-based human karyotype.

Abstract: Image cytometry and computer analysis are used to determine the relative DNA content and the DNA-based centromeric index of the 24 chromosomes of the human karyotype A two-step procedure is used Chromosomes of cells in metaphase first are stained with quinacrine and identified visually by their fluorescent Q-band patterns They then are stained for DNA using gallocyanin-chrome alum The chromosome images are scanned and recorded as digital values of optical density by an CYDAC image cytometric microscope system, CYDAC The digital images are processed by computer to measure for each chromosome the relative DNA stain contents of the whole chromosome and of the p and q arms and the DNA-based centromeric index About ten cells are analyzed for each of the donors, who are phenotypically normal men and women The chromosome measurements are pooled by chromosome type for each donor and are compared among donors The means of the chromosome measurements give the DNA-based human karyotype Analysis of the DNA-based data shows that some chromosomes or portions of chromosomes vary significantly among donors These variants do not correlate with detectable morphologic polymorphisms, such as Q- or C-band variants; thus they represent new and otherwise undetectable chromosome polymorphisms whose genetic basis and clinical significance are yet to be determined

Localization of the polymorphic human calcitonin gene on chromosome 11

Abstract: A molecular probe containing a 584 base pairs sequence corresponding to part of the human calcitonin mRNA was used for the chromosomal assignment of the calcitonin gene. Restriction endonuclease analysis of DNA from human-Chinese hamster and human-mouse somatic cell hybrids, including some containing a translocation of human chromosomes, placed the calcitonin gene in the p14→qter region of chromosome 11.

An extra segment in chromosome 1 of wild Mus musculus: a C-band positive homogeneously staining region.

Abstract: An extra segment in chromosome 1 between bands C5 and D has been found in wild mouse populations. Its size varies between 6.1 % and 30.1 % of the length of a standard chromosome 1. It differs among in

The gene and the pseudogene for mouse p53 cellular tumor antigen are located on different chromosomes.

Abstract: The chromosomal assignments of the two genes encoding the murine p53 cellular tumor antigen were determined by using a panel of mouse-Chinese hamster somatic cell hybrid clones and a mouse p53-specific cDNA clone. One gene, probably the functional member of the family, was found to be on chromosome 11. The other gene, which is probably a processed pseudogene, was assigned to chromosome 14. The potential relevance of these findings to documented cases of chromosome 11 trisomy are also discussed.