Search PubMed⌕ Search

Biomedical subjects

D E Barton

Publications and source records attributed to D E Barton.

At least 19 recordsLinked to original sources
PubMed1992

Presymptomatic diagnosis of von Hippel-Lindau disease with flanking DNA markers.

Von Hippel-Lindau (VHL) disease is a dominantly inherited cancer syndrome characterised by the development of retinal, cerebellar, and spinal haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25-p26 and flanking markers identified. We have investigated the usefulness of currently available DNA markers for the presymptomatic diagnosis of VHL disease. In the first part of this investigation, genetic linkage data from two previously published studies were updated and reanalysed to provide accurate estimates of sex specific recombination fractions and to confirm that there is no evidence of locus heterogeneity. In the second part of this study, 14 families containing 23 asymptomatic subjects at 50% prior risk of VHL disease were investigated with closely linked DNA markers (RAF1, D3S18, D3S732). Seventeen subjects were informative with one or more markers, six of whom were informative at markers flanking the VHL disease gene. By combining age related and DNA based risk information the carrier risk for 11 subjects was reduced to < 2%.

Adolescent↗
PubMed1990

Molecular analysis of the Mov 34 mutation: transcript disrupted by proviral integration in mice is conserved in Drosophila.

The Mov 34 mutation is a recessive embryonic lethal mutation caused by retroviral integration in the murine germline. This integration disrupts a transcription unit that appears to encode a novel protein. The Mov 34 proviral integration is located on mouse chromosome 8 and the human homolog of this gene has been mapped to chromosome region 16q23-q24. An evolutionarily conserved syntenic relationship exists between this region of human chromosome 16 and a region of mouse chromosome 8 that also contains oligosyndactyly (Os), another recessive lethal mutation. Genetic studies have ruled out Os as residing at the same locus as the Mov 34 integration. The Mov 34 transcript is conserved in evolution, and a Drosophila homolog appears to encode a protein with 62% amino acid identity to the murine protein. In situ hybridization to Drosophila polytene chromosomes localizes the Drosophila homolog to 60B,C on chromosome 2. Several Drosophila lethal mutations also map to this region.

Alleles↗
PubMed1989

Blast-1 possesses a glycosyl-phosphatidylinositol (GPI) membrane anchor, is related to LFA-3 and OX-45, and maps to chromosome 1q21-23.

Blast-1 is a human activation-associated glycoprotein expressed on the surface of leukocytes. Analysis of a translated sequence from a Blast-1 cDNA reveals a single hydrophobic sequence which could traverse the plasma membrane, but is devoid of charged residues that might represent a cytoplasmic tail. Consistent with this characteristic, Blast-1 is demonstrated here to be anchored to the cell surface through a glycosyl-phosphatidylinositol (GPI)-containing lipid. Comparison of Blast-1 to other GPI-anchored membrane proteins revealed a striking primary and secondary structure similarity with MRC OX45 and the lymphocyte function antigen LFA-3. The degree of overall amino acid sequence homology reveals that OX45 is a rat homologue of Blast-1. The greatest homology to LFA-3 occurs between their NH2-terminal Ig-like domains. Evidence is presented that demonstrates that Blast-1 and LFA-3 possess a disulfide-bonded second domain. These common characteristics demonstrate a structural and evolutionary relationship between Blast-1, OX45, LFA-3, and CD2, which in turn suggests a functional role for Blast-1 in cell-cell interactions in the immune response. The gene for Blast-1 has been localized to chromosome 1 q21-q23, indistinguishable from the CD1 cluster of Ig superfamily genes, raising the possibility that they may be linked.

Amino Acid Sequence↗
PubMed1989

Level of expression and chromosome mapping of the mouse cholecystokinin gene: implications for murine models of genetic obesity.

Cholecystokinin (CCK) is a neuropeptide which is present in brain and intestine and which stimulates gall bladder contraction and pancreatic secretion. Additional studies have demonstrated an appetite-suppressing effect of CCK in vivo. These data have aroused speculation that the physiology of this hormone could be relevant in the pathogenesis of the mouse obesity mutations ob on chromosome 6 and db on chromosome 4. In order to determine whether abnormalities of this hormone could be the primary defect in these obesity mutations, we have used three separate approaches to map the mouse Cck gene to distal chromosome 9, where it is part of a syntenic group between mouse chromosome 9 and human chromosome 3. These data therefore exclude cholecystokinin as the etiologic factor in the pathogenesis of any of the known mouse obesity syndromes. In order to exclude the possibility that there are differences in mutant animals in the level of CCK RNA, we have used an S1 nuclease protection assay as well as a novel radioimmunoassay that detects the CCK precursor, to show that there are no gross differences in CCK mRNA or protein precursor levels between ob/ob and wild-type animals.

Alleles↗
PubMed1989

Mapping of genes for inhibin subunits alpha, beta A, and beta B on human and mouse chromosomes and studies of jsd mice.

Inhibin (INH) is a gonadal glycoprotein hormone that regulates pituitary FSH secretion and may also play a role in the regulation of androgen biosynthesis. There are two forms of inhibin that strongly inhibit pituitary FSH secretion. These share the same alpha subunit that is covalently linked to one of two distinct beta subunits (beta A or beta B). However, dimers of two beta subunits are potent stimulators of FSH synthesis and release in vitro. The beta subunits share extensive sequence similarity with transforming growth factor beta. Recently isolated cDNAs for all three inhibin subunits have been used to map their cognate loci on human and mouse chromosomes by Southern blot analysis of somatic cell hybrid DNAs and by in situ hybridization. INH alpha and INH beta B genes were assigned to human chromosome 2, regions q33----qter and cen----q13, respectively, and to mouse chromosome 1. The INH beta A locus was mapped to human chromosome 7p15----p14 and mouse chromosome 13. The region of mouse chromosome 1 that carries other genes known to have homologs on human chromosome 2q includes the jsd locus (for juvenile spermatogonial depletion). Adult jsd/jsd mice have elevated levels of serum FSH and their testes are devoid of spermatogonial cells. The possibility that the mutation in jsd involves the INH alpha or INH beta B gene was investigated by Southern blotting of DNA from jsd/jsd mice, and no major deletions or rearrangements were detected.

Animals↗
PubMed1989

Human SSAV-related endogenous retroviral element: LTR-like sequence and chromosomal localization to 18q21.

A new family of human endogenous retroviral sequences was recently discovered by way of its relationship to the simian sarcoma-associated virus (SSAV). One molecular clone, termed S71, contains sequences related to the genes coding for the group-specific antigens (gag) and polymerase (pol) proteins of SSAV. At the 3' end of this human retroviral element we have now found a 535-bp region which shows features characteristics of a retroviral long terminal repeat, including potential signal sequences essential for transcriptional control. By means of Southern blotting and in situ hybridization, the sequence was mapped to chromosome 18 band q21.

Animals↗
PubMed1989

Isolation, chromosomal mapping, and expression of the mouse tyrosinase gene.

Using a human tyrosinase cDNA probe, we have isolated mouse tyrosinase genomic clones and used them to map the mouse tyrosinase locus and to analyze the promoter sequence of the tyrosinase gene. Southern blot analyses of DNA from somatic cell hybrids, interspecies backcross mice, and albino deletion mice have revealed that the locus for mouse tyrosinase resides at or near the albino locus on mouse chromosome 7. There were three TATA-elements, but only one CAT-element, and the CAT-element appeared to be paired with the third TATA-element, located at the position farthest upstream. Mouse tyrosinase mRNA is approximately 2.4 Kb in size. The amount of tyrosinase mRNA reflects the levels of tyrosinase activity in normal melanocytes and Cloudman S-91 melanoma cell line.

Albinism↗
PubMed1989

Chromosome mapping of the growth hormone receptor gene in man and mouse.

Pituitary growth hormone (GH) is essential for normal growth and development in animals and GH deficiency leads to dwarfism. This hormone acts via specific high-affinity cell surface receptors found in liver and other tissues. The recent cloning and sequencing of cDNAs encoding human and rabbit GH receptors (GHR) has demonstrated that this receptor is unrelated to any previously described cell membrane receptor or growth factor receptor. We have used the cloned human GHR cDNA to map the GHR locus to the proximal short arm of human chromosome 5, region p13.1----p12, and to mouse chromosome 15 by Southern blot analysis and in situ hybridization. While human chromosome 5 carries several genes for hormone and growth factor receptors, GHR is the only growth-related gene so far mapped to the short arm. Inasmuch as GHR is the first gene with apparently homologous loci on human chromosome 5 and mouse chromosome 15, it identifies a new homologous conserved region. In humans, deficiency of GH receptor activity probably causes Laron-type dwarfism, an autosomal recessive disorder prevalent in Oriental Jews. In mice, the autosomal recessive mutation miniature (mn) is characterized by severe growth failure and early death and has been mapped to chromosome 15. Our assignment of Ghr to mouse chromosome 15 suggests this as a candidate gene for the mn mutation.

Animals↗
PubMed1988

Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin.

Melanoma growth stimulatory activity (MGSA) is a mitogenic polypeptide secreted by Hs294T human melanoma cells. Comparison of the N-terminal sequences of the 13 and 16 kd MGSA species with the cDNA sequence revealed that the mature form of human MGSA is maximally 73 amino acids long. Expression of the cDNA in mammalian cells results in the secretion of this peptide with mitogenic activity. MGSA is structurally related to the platelet-derived beta-thromboglobulin and to several other polypeptides. These factors may constitute a family of growth factors. MGSA mRNA was detected in a variety of cell types. The level of MGSA mRNA in melanoma cells is strongly elevated by treatment with MGSA. MGSA is the gene product of a recently detected gene gro. The gene was mapped to chromosome 4 (region q13----q21). This same region also contains genes for two of the structurally related factors, for c-kit, a receptor for an as yet unidentified ligand, and for 'piebald trait', an inherited skin pigmentation disorder.

Amino Acid Sequence↗
PubMed1988

Assignment of the T-cell differentiation gene MAL to human chromosome 2, region cen----q13.

A cDNA clone has recently been isolated that encodes a protein expressed only in the intermediate and late stages of T-cell differentiation, termed MAL. The polypeptide deduced from the MAL cDNA sequence contains four potential transmembrane domains. We have used a panel of 28 human X rodent hybrid cell lines to assign the MAL gene to the proximal long arm of human chromosome 2, region cen----q13. The significance of the MAL map position and its relationship with other genes on chromosome 2 are discussed.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Chromosomal mapping of the gene for the type II insulin-like growth factor receptor/cation-independent mannose 6-phosphate receptor in man and mouse.

The gene for insulin-like growth factor II (IGF-II) receptor (IGF2R) that has recently been found, by DNA sequencing, to be identical to the cation-independent mannose 6-phosphate receptor (CIM6PR) has been mapped in the human and murine species. Cloned cDNAs for human and rat IGF-II receptors were used to probe Southern blots of somatic cell hybrid DNA and for in situ chromosomal hybridization. The genes are located in a region of other conserved syntenic genes on the long arm of human chromosome 6, region 6q25----q27, and mouse chromosome 17, region A-C. The CIM6PR/IGF2R locus in man is asyntenic with the genes encoding IGF-II (IGF2), the IGF-I receptor (IGF1R), and the cation-dependent mannose 6-phosphate receptor (CDM6PR).

Animals↗
PubMed1988

Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7.

The enzyme tyrosinase (monophenol,L-dopa:oxygen oxidoreductase; EC 1.14.18.1) catalyzes the first two steps in the conversion of tyrosine to melanin, the major pigment found in melanocytes. Some forms of oculocutaneous albinism, characterized by the absence of melanin in skin and eyes and by a deficiency of tyrosinase activity, may result from mutations in the tyrosinase structural gene. A recently isolated human tyrosinase cDNA was used to map the human tyrosinase locus (TYR) to chromosome 11, region q14----q21, by Southern blot analysis of somatic cell hybrid DNA and by in situ chromosomal hybridization. A second site of tyrosinase-related sequences was detected on the short arm of chromosome 11 near the centromere (p11.2----cen). Furthermore, we have confirmed the localization of the tyrosinase gene in the mouse at or near the c locus on chromosome 7. Comparison of the genetic maps of human chromosome 11 and mouse chromosome 7 leads to hypotheses regarding the evolution of human chromosome 11.

Animals↗
PubMed1988

Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome that appears to be mediated in many instances by a parathyroid hormone-like peptide. Poly(A)+ RNA from a human renal carcinoma associated with this syndrome was enriched by preparative electrophoresis and used to construct an enriched cDNA library in phage lambda gt10. The library was screened with a codon-preference oligonucleotide synthesized on the basis of a partial N-terminal amino acid sequence from a human tumor-derived peptide, and a 2.0-kilobase cDNA was identified. The cDNA encodes a 177 amino acid protein consisting of a 36 amino acid leader sequence and a 141 amino acid mature peptide. The first 13 amino acids of the deduced sequence of the mature peptide display strong homology to human PTH, with complete divergence thereafter. RNA blot-hybridization analysis revealed multiple transcripts in mRNA from tumors associated with the humoral syndrome and also in mRNA from normal human keratinocytes. Southern blot analysis of genomic DNA from humans and rodents revealed a simple pattern compatible with a single-copy gene. The gene has been mapped to chromosome 12.

Amino Acid Sequence↗
PubMed1988

Chromosomal mapping of genes for transforming growth factors beta 2 and beta 3 in man and mouse: dispersion of TGF-beta gene family.

Human cDNA probes for two new types of transforming growth factor-beta, TGF-beta 2 and TGF-beta 3, were used for mapping their cognate genes on human and mouse chromosomes by Southern blot analysis of somatic cell hybrid lines and, for the human loci, also by in situ chromosomal hybridization. For TGF-beta 2, a single site was found on the long arm of human chromosome 1, band 1q41, and on mouse chromosome 1, most likely in the known conserved syntenic region. For TGF-beta 3, the major site of hybridization, both on Southern filters and direct chromosome preparations, was at 14q24 in humans. This region is homologous in part to mouse chromosome 12, to which the murine beta 3 locus was mapped. These results indicate a wide dispersion of the TGF-beta gene family, with genes for TGF-beta 1 previously mapped by us to human chromosome 19q and mouse chromosome 7 and for inhibins alpha, beta B and beta A to human chromosomes 2q33-qter, 2cen-q13 and 7p15-p13, respectively.

Animals↗
PubMed1987

The human U1-70K snRNP protein: cDNA cloning, chromosomal localization, expression, alternative splicing and RNA-binding.

We have isolated and sequenced cDNA clones encoding the human U1-70K snRNP protein, and have mapped this locus (U1AP1) to human chromosome 19. The gene produces two size classes of RNA, a major 1.7-kb RNA and a minor 3.9-kb RNA. The 1.7-kb species appears to be the functional mRNA; the role of the 3.9-kb RNA, which extends further in the 5' direction, is unclear. The actual size of the hU1-70K protein is probably 52 kd, rather than 70 kd. The protein contains three regions similar to known nucleic acid-binding proteins, and it binds RNA in an in vitro assay. Comparison of the cDNA sequences indicates that there are multiple subclasses of mRNA that arise by alternative pre-mRNA splicing of at least four alternative exon segments. This suggests that multiple forms of the hU1-70K protein may exist, possibly with different functions in vivo.

Amino Acid Sequence↗
PubMed1987

Activation of human alpha 1-antitrypsin genes in rat hepatoma x human fibroblast hybrid cell lines is correlated with demethylation.

Alpha-1-antitrypsin (AAT) is the major protease inhibitor in human serum and is primarily expressed in the liver. We have studied AAT expression in fusion hybrids between a rat hepatoma line and either human fetal liver fibroblasts (series XXII) or human skin fibroblasts (series XIX). While the human AAT gene was always activated in series XXII hybrids when it was present, it was only rarely activated in series XIX hybrids. RFLP analysis revealed that both parental AAT alleles in series XIX hybrids were capable of being activated. Molecular analysis of the AAT gene in expressing and nonexpressing hybrids revealed that active AAT genes were hypomethylated, while inactive AAT genes were highly methylated. However, differences in methylation patterns were confined to the 5' end of the gene, on both sides of the first exon. DNaseI sensitivity revealed no hypersensitive sites close to active or inactive AAT genes.

Animals↗
PubMed1987

The myelin-associated glycoprotein gene: mapping to human chromosome 19 and mouse chromosome 7 and expression in quivering mice.

Myelin-associated glycoprotein (MAG), a membrane glycoprotein of 100 kDa, is thought to be involved in the process of myelination. A cDNA encoding the amino-terminal half of rat MAG has recently been isolated and sequenced. We have used this cDNA in Southern blot analysis of DNA from 32 somatic cell hybrids to assign the human locus for MAG to chromosome 19 and the mouse locus to chromosome 7. Since the region of mouse chromosome 7-known to contain several other genes that are homologous to genes on human chromosome 19-also carries the quivering (qv) locus, we considered the possibility that a mutation in the MAG gene could be responsible for this neurological disorder. While MAG-specific DNA restriction fragments, mRNA, and protein from qv/qv mice were apparently normal in size and abundance, we have not ruled out the possibility that qv could be caused by a point mutation in the MAG gene.

Animals↗