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Biomedical subjects

T B Shows

Publications and source records attributed to T B Shows.

At least 271 records · Page 15Linked to original sources
PubMed1984

Human metallothionein genes are clustered on chromosome 16.

The metallothioneins are a family of heavy-metal binding proteins of low molecular weight. They function in the regulation of trace metal metabolism and in the protection against toxic heavy metal ions. In man, the metallothioneins are encoded by at least 10-12 genes separated into two groups, MT-I and MT-II. To understand the genomic organization of these genes and their involvement in hereditary disorders of trace metal metabolism, we have determined their chromosomal location. Using human-mouse cell hybrids and hybridization probes derived from cloned and functional human MT1 and MT2 genes, we show that the functional human genes are clustered on human chromosome 16. Analysis of RNA from somatic cell hybrids indicated that hybrids that contained human chromosome 16 expressed both human MT1 and MT2 mRNA, and this expression is regulated by both heavy metal ions and glucocorticoid hormones.

Animals↗
PubMed1984

DNA polymorphic loci mapped to human chromosomes 3, 5, 9, 11, 17, 18, and 22.

Using the techniques of Southern filter hybridization and somatic cell genetics, seven genomic DNA fragments recognizing DNA polymorphic loci were mapped to specific chromosomes and regions of chromosomes. The seven probes, isolated from human genomic libraries, lacked repetitive sequences and were hybridized to DNA isolated from a set of human-rodent somatic cell hybrids segregating human chromosomes. These probes detected DNA sequences on human chromosomes 3, 5, 9, 11, 17, 18, and 22. These DNA polymorphic sites, which occur in 10% or greater of the population, will serve as markers for linkage studies with known polymorphic loci as well as to establish linkage with disease loci.

Animals↗
PubMed1984

Assignment of the gene for methylthioadenosine phosphorylase to human chromosome 9 by mouse-human somatic cell hybridization.

The purine and polyamine metabolic enzyme methylthioadenosine (MeSAdo) phosphorylase is abundant in normal cells and tissues but is lacking from many human and murine malignant cell lines and from cells of some human leukemias in vivo. To explore the genetic control of MeSAdo phosphorylase expression, we measured levels of the enzyme in somatic cell hybrids prepared by fusing MeSAdo phosphorylase-deficient mouse L cell lines with human fibroblasts. In the hybrid clones, MeSAdo phosphorylase activity segregated concordantly with adenylate kinase 1, a marker for human chromosome 9, but not with enzyme markers for any other human chromosome. In hybrid clones derived from human fibroblasts with a reciprocal translocation between chromosomes 9 and 17, MeSAdo phosphorylase activity was confined to cells containing the 9pter----9q12 region. In every case, the enzyme-positive hybrid clones displayed bands of MeSAdo phosphorylase activity with isoelectric points characteristic of both the human and murine enzymes. These results indicate that the structural gene for human MeSAdo phosphorylase, designated MTAP, can be assigned to the 9pter----9q12 region of human chromosome 9. Furthermore, these studies with interspecies somatic cell hybrids show that the MeSAdo phosphorylase-deficient state is recessive in mouse L cell lines.

Adenosine↗
PubMed1984

The human glucagon gene is located on chromosome 2.

DNA samples prepared from a panel of human-mouse cell hybrids with different numbers and combinations of human chromosomes were examined for the presence of the human preproglucagon gene by hybridization with a cloned segment of the human gene. The segregation of the human glucagon gene specific DNA fragment and human chromosome 2 in these cell hybrids indicated that the preproglucagon gene (designated GCG) is on chromosome 2 in humans.

Animals↗
PubMed1983

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

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.

Animals↗
PubMed1983

Human c-Ki-ras2 proto-oncogene on chromosome 12.

A human colonic adenocarcinoma transforming gene, recently identified as a cellular homolog of the Kirsten sarcoma gene (v-ras), was used to assign the human cellular Kirsten ras2 gene to chromosome 12 by the Southern hybridization method. A single 640 base-pair Eco RI--Hind III fragment of the transforming gene, isolated by DNA transfection and molecular cloning, can detect a single Eco RI fragment (2.9 kilobase pairs) of DNA from phenotypically normal cells. The data suggest a constant chromosomal location of c-Ki-ras2.

Adenocarcinoma↗
PubMed1983

Human immune interferon gene is located on chromosome 12.

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.

Animals↗
PubMed1983

Human parathyroid hormone gene (PTH) is on short arm of chromosome 11.

The human gene for parathyroid hormone (PTH) was chromosomally mapped using human-rodent hybrids and Southern filter hybridization of cell hybrid DNA. A recombinant DNA probe containing human PTH cDNA insert (pPTHm122) hybridized to a 3.7-kb fragment in human DNA cleaved with the restriction enzyme EcoRI. By correlating the presence of this fragment in somatic cell hybrid DNA with the human chromosomal content of the hybrid cells, the PTH gene was mapped to the short arm of the chromosome 11.

Animals↗
PubMed1983

Relationship between H1 histone phosphorylation and genome replication in a mouse-Chinese hamster somatic cell hybrid.

The relationship between stable genome replication and the presence of species-specific H1 and H2b histones was studied in a mouse-Chinese hamster somatic cell hybrid (LMC-1). LMC-1 contained the complete chromosome complements of the mouse (LM/TK-, 46 chromosomes) and Chinese hamster (CHW-1102, 22 chromosomes) parents. No chromosome loss occurred in over a year in continuous culture, and both mouse and Chinese hamster enzymes were expressed. Chromatographic resolution of H1 histone subtypes showed that only mouse H1 genes were expressed. Resolution of chromatographically purified H2b histone variants using Triton X-100-containing gels also demonstrated that LMC-1 cells made mouse, not Chinese hamster, H2b histones. Species-specific tryptic phosphopeptides were resolved from purified H1 histones using high voltage paper electrophoresis. These studies demonstrated that characteristic mouse, but not Chinese hamster, phosphopeptides were formed in H1 histones in actively-growing LMC-1 cells. We conclude that the Chinese hamster genome may replicate in a stable manner in the presence of mouse H1 (and H2b) histones, and that there is no obligatory relationship between species-specific phosphorylation of H1 histones and stable genome replication.

Animals↗
PubMed1983

The tumor phenotype and the human gene map.

The tumor phenotype is associated with the rearrangement of genetic information and the altered expression of many gene products. In this review, genes associated with the tumor phenotype have been arranged on the human gene map and indicate the extent to which the tumor phenotype involves the human genome. Nonrandom chromosomal aberrations that are frequently observed in tumors are presented. Altered metabolic demands of the tumor cell are reflected in altered gene expressions of a wide range of enzymes and other proteins, and these changed enzyme patterns are described. The study of oncogenes increasingly suggests that they may be significant in certain cancers, and the assignment of these genes has been tabulated. The biochemical and metabolic changes observed in tumors are complex; studying the patterns and interactions of these changes will aid our genetic understanding of the origins and development of tumors.

Carcinoembryonic Antigen↗
PubMed1983

Chromosomal assignment of the gene for the human beta 2-adrenergic receptor.

Chinese hamster fibroblasts (CHW) fail to physiologically respond to the beta-adrenergic agonist isoproterenol with an increase in cellular cAMP. This unresponsiveness is due to a lack of beta-adrenergic receptors as indicated by an absence of specific binding of 125I-labeled hydroxybenzylpindolol (125I-HYP) to CHW plasma membranes. Preparation of somatic cell hybrids between CHW and human peripheral blood leukocytes led to the selection of a panel of 15 human-Chinese hamster cell hybrid clones, some of which had beta 2-adrenergic receptors (specifically bound 125I-HYP) and responded to isoproterenol (accumulated cAMP). Biochemical analysis of independent cloned cell hybrids indicated that beta 2-adrenergic receptor density and the intensity of the associated physiological response were closely correlated (r = 0.98). Both of these parameters were concordant in all cell hybrids with the presence of human chromosome 5. All other human chromosomes could be ruled out. These results suggest that the structural gene for the beta 2-adrenergic receptor is found on human chromosome 5.

Adenylyl Cyclases↗
PubMed1983

Polymorphic gene for human carbonic anhydrase II: a molecular disease marker located on chromosome 8.

A panel of 28 mouse-human somatic cell hybrids of known karyotype was screened for the presence of the human carbonic anhydrase II (CA II) gene, which encodes one of the three well-characterized, genetically distinct carbonic anhydrase isozymes (carbonate dehydratase; carbonate hydro-lyase, EC 4.2.1.1). The human and mouse CA II genes can be clearly distinguished by Southern blot analysis of BamHI-digested genomic DNA with a mouse CA II cDNA hybridization probe. The two major hybridizing fragments in mouse were 15 and 6.0 kilobase pairs, and in human they were 15 and 4.3 kilobase pairs. Analysis of the somatic cell hybrids by this technique identified those containing human CA II gene sequences. Segregation analysis of the molecular marker and chromosomes in cell hybrids indicated a clear correlation between the presence of chromosome 8 and the human CA II gene (CA2). This finding provides the second polymorphic marker for human chromosome 8 and, moreover, a molecular disease marker, because human CA II deficiency has recently been linked to an autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification.

Animals↗
PubMed1983

Two nonallelic tRNAiMet genes are located in the p23 leads to q12 region of human chromosome 6.

Two nonallelic human tRNAiMet genes were assigned to chromosome 6 by filter hybridization of DNA from human-rodent somatic cell hybrids by using probes containing unique sequences from the regions flanking each tRNAiMet gene. These unique sequence probes thus allowed each tRNAiMet gene to be analyzed individually in cell hybrids. Both tRNAiMet genes segregated in the hybrid cells with the chromosome 6 enzyme markers, soluble malic enzyme and the mitochondrial form of superoxide dismutase, and also with a karyotypically normal chromosome 6. By using hybrid clones containing translocations that divide chromosome 6 into five segments, both tRNAiMet genes were assigned to the p23 leads to q12 region. These results raise the possibility that other tRNAiMet genes may be syntenic with the two described in this study and illustrate the utility of using unique flanking sequences to identify members of a multigene family.

Alleles↗
PubMed1983

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

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.

Amylases↗
PubMed1983

Polymorphic human somatostatin gene is located on chromosome 3.

Somatostatin is a 14-amino-acid neuropeptide and hormone that inhibits the secretion of several peptide hormones. The human gene for somatostatin SST has been cloned, and the sequence has been determined. This clone was used as a probe in chromosome mapping studies to detect the human somatostatin sequence in human-rodent hybrids. Southern blot analysis of 41 hybrids, including some containing translocations of human chromosomes, placed SST in the q21 leads to qter region of chromosome 3. Human DNAs from unrelated individuals were screened for restriction fragment polymorphisms detectable by the somatostatin gene probe. Two polymorphisms were found: (i) an EcoRI variant located at the 3' end of the gene, found in Caucasian, U.S. Black, and Asian populations with a frequency of approximately 0.10 and (ii) a BamHI variant in the intron, which occurs in Caucasians at a frequency of 0.13.

Animals↗
PubMed1983

Assignment of the human phosphoserine phosphatase gene (PSP) to the pter leads to q22 region of chromosome 7.

Phosphoserine phosphatase (PSP) catalyzes the hydrolysis of phosphoserine to serine. PSP expression has been examined in human-mouse somatic cell hybrids retaining different combination of human chromosomes. Human PSP is expressed only when the pter leads to q22 segment of the human 7 and its enzyme marker beta-glucuronidase (GUSB) are retained in cell hybrids. The structural gene, PSP, is therefore assigned to this region of the human 7.

Animals↗