Histone genes were mapped to at least three human chromosomes by Southern blot analysis of DNAs from a series of mouse-human somatic cell hybrids (using 32P-labeled cloned human histone DNA as probes). Chromosome assignment was confirmed by in situ hybridization of radiolabeled histone gene probes (3H-labeled) to metaphase chromosomes. One human histone gene cluster (lambda HHG41) containing an H3 and H4 gene resides only on chromosome 1, whereas other clusters containing core (H3, H4, H2A, and H2B) alone (lambda HHG17) or core together with H1 histone genes (lambda HHG415) have been assigned to chromosomes 1, 6, and 12. These results suggest that the multigene family of histone coding sequences that reside in a series of clusters may be derived from a single cluster containing one each of the genes for the five principal classes of histone proteins. During the course of evolution, a set of events, probably involving reduplication, sequence modification, and recombination, resulted in the present pattern of human histone gene distribution among several chromosomes.

Biological Evolution↗

PubMed1986

The gene encoding the T-cell surface protein T4 is located on human chromosome 12.

The surface glycoproteins T4 and T8 define functionally distinct populations of T lymphocytes. We have obtained cDNA and genomic clones encoding the T4 molecule and used these as probes to determine the chromosomal location of this gene. Genomic blotting experiments, along with in situ hybridization analyses, indicate that the T4 gene resides on the short arm of human chromosome 12, at region p12-pter. Thus, the T4 gene is not linked to any known member of the immunoglobulin gene family, including its counterpart gene, T8, which resides on human chromosome 2 immediately distal to the immunoglobulin kappa locus.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1986

Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma.

We have determined that the bcl-2 (B-cell leukemia/lymphoma 2) gene is transcribed into three overlapping mRNAs, and we have cloned bcl-2 cDNA sequences. Sequence analysis of the bcl-2 cDNA clones and comparison of their sequences to their genomic counterparts indicate that the bcl-2 gene contains at least two exons. The three bcl-2 transcripts, which are 8.5, 5.5, and 3.5 kilobases (kb) long, overlap within the first exon, but only the 8.5-kb and 5.5-kb transcripts contain sequences of the second exon. The 8.5-kb and 5.5-kb transcripts seem to use different polyadenylylation sites. Sequence analysis of the cDNA clones corresponding to the 5.5-kb and 3.5-kb mRNAs indicates that the two bcl-2 transcripts carry two overlapping open reading frames, one of which is 717 nucleotides long and codes for a protein (bcl-2 alpha) of 239 amino acids and a molecular mass of 26 kDa, while the other codes for a protein of 205 amino acids (bcl-2 beta, molecular mass 22 kDa) that is identical to bcl-2 alpha except at the carboxyl terminus. The bcl-2 protein products in follicular lymphomas with or without bcl-2 rearrangements are identical to the normal bcl-2 products.

Base Sequence↗

PubMed1986

The human c-ros gene (ROS) is located at chromosome region 6q16----6q22.

The human homolog, c-ros, of the transforming gene, v-ros, of the avian sarcoma virus, UR2, has been isolated from a human genomic library. A single-copy fragment from the human c-ros genomic clone has been used to map the human c-ros homolog (ROS) to human chromosome region 6q16----6q22 by somatic cell hybrid analysis and chromosomal in situ hybridization. Thus, the c-ros gene joins the c-myb oncogene, which is distal to the c-ros gene on the long arm of human chromosome 6, as a candidate for involvement in chromosome 6q deletions and rearrangements seen in various malignancies.

Chromosome Mapping↗

PubMed1986

Molecular cloning and nucleotide sequence of a full-length cDNA for human alpha enolase.

We previously purified a 48-kDa protein (p48) that specifically reacts with an antiserum directed against the 12 carboxyl-terminal amino acids of the c-myc gene product. Using an antiserum directed against the purified p48, we have cloned a cDNA from a human expression library. This cDNA hybrid-selects an mRNA that translates to a 48-kDa protein that specifically reacts with anti-p48 serum. We have isolated a full-length cDNA that encodes p48 and spans 1755 bases. The coding region is 1299 bases long; 94 bases are 5' noncoding and 359 bases are 3' noncoding. The cDNA encodes a 433 amino acid protein that is 67% homologous to yeast enolase and 94% homologous to the rat non-neuronal enolase. The purified protein has been shown to have enolase activity and has been identified to be of the alpha type by isoenzyme analysis. The transcriptional regulation of enolase expression in response to mitogenic stimulation of peripheral blood lymphocytes and in response to heat shock is also discussed.

Amino Acid Sequence↗

PubMed1986

Regulation of translocated c-myc genes transfected into plasmacytoma cells.

We have transfected two translocated c-myc oncogene clones, derived from two human lymphomas carrying the t(8;14) chromosome translocation, into mouse plasmacytoma cells to study the regulation of their expression. In one case, the transfected clone contained the two coding exons of the c-myc oncogene translocated to an immunoglobulin heavy-chain switch region; in the other case, the two coding exons were translocated 5' of the enhancer element located between the heavy-chain joining region (JH) and the switch region S mu. Nuclease S1 protection experiments indicate that only the c-myc translocated 5' of the enhancer element is transcribed in the plasmacytoma cells. Thus, 5'-truncation of the c-myc gene per se does not lead to c-myc deregulation. Further, since the level of c-myc transcripts in the parental human lymphoma cells was 3- to 4-fold higher than in the transfectants, it seems likely that additional elements within the heavy-chain locus may play a role in the enhancement of c-myc gene transcription in lymphoma cells.

Animals↗

PubMed1986

Heterogeneity of chromosome 22 breakpoint in Philadelphia-positive (Ph+) acute lymphocytic leukemia.

In chronic myelogenous leukemias (CML) with the t(9;22)(q34;q11) chromosome translocation the breakpoints on chromosome 22 occur within a 5.8-kilobase segment of DNA referred to as "breakpoint cluster region" (bcr). The same cytogenetically indistinguishable translocation occurs in approximately 10% of patients with acute lymphocytic leukemias (ALL). In this study we have investigated the chromosome breakpoints in several cases of ALL carrying the t(9;22) translocation. In three of five cases of ALL we found that the bcr region was not involved in the chromosome rearrangement and that the 22q11 chromosome breakpoints were proximal (5') to the bcr region at band 22q11. In addition, we observed normal size bcr and c-abl transcripts in an ALL cell line carrying the t(9;22) translocation. We conclude, therefore, that if c-abl is inappropriately expressed in ALL cells without bcr rearrangements, the genetic mechanism of activation must be different from that reported for CML.

Adolescent↗

PubMed1986

Localization of the human pim oncogene (PIM) to a region of chromosome 6 involved in translocations in acute leukemias.

The human homolog, hpim, of the murine pim-1 gene, which is activated in murine T-cell lymphomas by insertion of retrovirus proviral genomes in the pim-1 region, has been molecularly cloned; the cloned probe has been used to map the hpim locus to human chromosome region 6p21 by somatic cell hybrid analysis and chromosomal in situ hybridization. The hpim gene is expressed as a 3.2-kilobase mRNA in various human cell lines of hematopoietic lineage, most dramatically in the K562 erythroleukemia cell line, which contains a cytogenetically demonstrable rearrangement in the 6p21 region. A characteristic chromosome anomaly, a reciprocal translocation t(6;9)(p21;q33), has been described in myeloid leukemias and could involve the hpim gene.

Chromosome Mapping↗

PubMed1986

Molecular genetics of human B- and T-cell neoplasia.

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B-Lymphocytes↗

PubMed1986

Tissue-type plasminogen activator gene is on chromosome 8.

Tissue plasminogen activator is one of the two plasminogen activators, both serine proteases, that catalyze the conversion of inactive plasminogen to plasmin, which then degrades the fibrin network of blood clots. By combining somatic cell genetics, in situ hybridization, and Southern blot hybridization, we localized the human tissue plasminogen activator gene to the pericentromeric region of chromosome 8.

Animals↗

PubMed1986

Chromosomal localization of a human band 3-like gene to region 7q35----7q36.

Band 3, the major transmembrane protein of erythrocytes, mediates the exchange of anions across the membrane and anchors the erythroid membrane skeleton. Proteins immunologically related to Band 3 have been detected in a variety of nonerythroid cells. We have isolated a human cDNA clone that encodes a protein related to but distinct from the erythroid form of Band 3, based on the comparison of the amino acid sequence for the two proteins. The presence of the gene for the Band 3-like protein in a panel of mouse-human somatic cell hybrids containing subsets of human chromosomes correlated with the presence of human chromosome 7. In situ hybridization analysis using the c-DNA for this nonerythroid Band 3 gene further localized the gene to region 7q35----7q36 of human metaphase chromosomes.

Animals↗

PubMed1986

Molecular genetics of human B cell neoplasia.

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B-Lymphocytes↗

PubMed1986

Molecular mechanisms involved in human B and T cell neoplasia.

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Animals↗

PubMed1986

Chromosomal approaches to the molecular basis of neoplasia.

Nonrandom patterns of chromosome abnormality in tumors are providing clues to the location of oncogenes and their activation mechanisms. Studies of translocations in Burkitt's lymphoma cells have shown that the c-myc proto-oncogene is consistently juxtaposed with a rearranged and transcriptionally active immunoglobulin gene locus, with resultant myc gene deregulation. In other B cell tumors, translocations appear to bring previously unrecognized oncogenes (bcl-1, bcl-2) into similar association with the immunoglobulin heavy-chain locus. T cell receptor genes may also "activate" known and unknown oncogenes after chromosome translocation. In chronic myelogenous leukemia, the translocated c-abl oncogene forms a "hybrid" gene in its new location on the Philadelphia chromosome, with altered function. Gene amplification units, seen as cytogenetically homogeneous staining regions in chromosomes or as double-minute bodies in metaphases, can represent multiple copies of oncogenes and be important in late stages of tumor progression. Other significant alterations in gene dosage, recognized as gain or loss of all or part of a specific chromosome, also occur in human neoplasms, but their specific role in carcinogenesis is largely undefined.

Burkitt Lymphoma↗