Showing papers by "Uta Francke published in 1983"

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.

Oncogene from human EJ bladder carcinoma is located on the short arm of chromosome 11

Abstract: The human cellular homolog of the transforming DNA sequence isolated from the bladder carcinoma cell line EJ was localized on the short arm of human chromosome 11 by Southern blot analysis of human-rodent hybrid cell DNA. This locus contains human sequences homologous to the Harvey murine sarcoma virus v-Ha-ras oncogene.

The c-Ha-ras1, insulin and beta-globin loci map outside the deletion associated with aniridia-Wilms' tumour.

Abstract: The localization of protooncogenes on human chromosomes may coincide with chromosome breakpoints of consistent translocations in leukaemias or lymphomas, suggesting a direct involvement of oncogenes in carcinogenesis. For example, in Burkitt's lymphoma consistent translocations may be associated with rearrangements of c-myc. Our assignment of the c-Harvey-ras1 oncogene to chromosome 11, precisely to region 11p11 leads to p15 (ref. 5; not 11p13 as stated in ref. 6), has raised the possibility that this oncogene might have a role in the predisposition to nephroblastoma (Wilms' tumour, WT) seen in the aniridia-WT association (AWTA) that is frequently caused by an interstitial deletion of band 11p (ref. 8). We have now studied the organization and copy number of sequences at three loci mapped to 11p: c-Ha-ras1, insulin and gamma-globin in cells from four individuals with structural rearrangements of the short arm of chromosome 11. Our results reported here rule out a close physical linkage between c-Ha-ras1 and the genes responsible for AWTA, and suggest a more distal localization of the beta-globin cluster than currently assumed.

Chromosome mapping of human cell surface molecules: Monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11

Abstract: Monoclonal antibodies 4F2, A3D8, and A1G3, directed against cell surface antigens present on subsets of human cells, were used to identify the human chromosome regions that code for the antigenic determinants. Human fibroblasts expressed all three antigens, and no cross-reactivity with Chinese hamster or mouse cells was found. Fourteen rodent x human somatic cell hybrids, derived from six different human donors and from two different Chinese hamster and one mouse cell line, were studied simultaneously for human chromosome content and for antibody binding as detected by indirect immunofluorescence. Concordancy with binding of all three antibodies was observed only for human chromosome 11. All other chromosomes were excluded by three or more discordant hybrid clones. Data from six hybrids containing three different regions of chromosome 11 indicate that it is the long arm of chromosome 11 which is both necessary and sufficient for expression of the human antigen defined by 4F2 while the antigen(s) defined by A3D8 and A1G3 map to short arm.

Regional assignment of the human gene for platelet-type phosphofructokinase (PFKP) to chromosome 10p: novel use of polyspecific rodent antisera to localize human enzyme genes

Abstract: Human phosphofructokinase (PFK; EC 2.7.1.11) is under the control of three structural loci which encode muscle-type (M), liver-type (L), and platelet or fibroblast-type (P) subunits; human diploid fibroblasts and leukocytes express all three loci. In order to assign the human PFKP locus to a specific human chromosome, in this study, we have examined ten human x rodent somatic cell hybrids for the expression of human P subunits using a mouse anti-human P subunit-specific antiserum in an active-enzyme-immunoprecipitation technique. In nine of ten hybrids studied, the expression of the PFKP locus segregated concordantly with chromosome 10 and none other, indicating that PFKP is located on chromosome 10; the discordancy rates for all the other chromosomes were 0.2 or greater. In the one discordant hybrid, only the long arm of chromosome 10 was retained and PFKP was not expressed. Human fibroblasts from a patient with duplication of the short arm of chromosome 10 consistently exhibited PFK activity values 180% of normal. These data indicate that human PFKP is located on the short arm of chromosome 10, and that a gene dosage effect is demonstrable in fibroblasts with a duplication of 10p. The use of rodent antihuman antibody combined with immunoprecipitation aided by staphylococci-bearing protein A may find general application in mapping human enzyme genes, when human and rodent geneproducts are not distinguishable by other means.

Activation of human alpha 1-antitrypsin gene in rat hepatoma x human fetal liver cell hybrids depends on presence of human chromosome 14.

Abstract: In order to study the involvement of human chromosomes in the expression of liver-specific functions, we have produced somatic cell hybrids between a rat hepatoma (7777) cell line and human diploid skin fibroblasts (series XIX) or human fetal liver cells (series XXII). Production of human serum proteins was detected by immunoelectrophoretic analyses of concentrated serum-free hybrid culture supernatants. Human α1-antitrypsin (AAT) was secreted by a subset of hybrids but not by the parental cells. The activated human AAT phenotype segregated concordantly with human chromosome 14 in 18 primarily HAT-selected and five azaguanine back-selected series XXII hybrids. All other chromosomes were excluded as playing a role in AAT expression. Therefore, the AAT gene PI is assigned to chromosome 14. This quasi-constitutive expression of a liver-specific function was not observed for the other serum proteins studied, nor was it seen in the skin fibroblast-derived hybrids (series XIX) although AAT was produced by some of them.

The N-ras oncogene assigned to the short arm of human chromosome 1

Abstract: The human N-ras oncogene, isolated from the HL-60 promyelocytic leukemia cell line, is distantly related to viral oncogenes of Kirsten and Harvey sarcoma viruses. We have determined its chromosomal location by Southern blot analysis of DNAs from 37 human x rodent hybrid cell lines derived from 8 different human donors, some of whom carried balanced rearrangements of chromosome 1. The results indicate that the N-ras oncogene (RASN) is localized on the proximal part of the short arm of human chromosome 1, in region p3200 leads to cen.

Aqueductal stenosis leading to hydrocephalus—an unusual manifestation of neurofibromatosis

Abstract: Two brothers and an unrelated male with neurofibromatosis (NF) developed hydrocephalus in childhood. Aqueductal stenosis (AS) was demonstrated by ventriculography and required shunt operation. Genetic counselors had to decide whether to invoke an X-linked gene for AS or whether AS could be caused by the NF mutation. Reports of 13 patients of both sexes with AS and NF suggest that AS with resulting hydrocephalus may be a rare manifestation of the NF gene. AS should be looked for in young NF patients with signs of hydrocephalus or with neurologic abnormalities.

Chromosomal assignments of three random RFLP loci defined by base-pair changes in MspI sites.

Abstract: Three cloned single copy sequences isolated from a random partial plasmid library of human EcoRI-HindIII restriction fragments detect MspI site polymorphisms in human DNA. Since at least two of them have allele frequencies that make them suitable for family linkage studies, we have determined their chromosomal localizations. DNA samples extracted from a panel of 31 Chinese hamster x human somatic cell hybrids, that were derived from six different human donors, were analyzed for the presence of human EcoRI or HindIII fragments hybridizing with the three probes. The results were correlated with the human chromosome contents of the hybrids. Concordancy was observed for clone pMS 1-14 (preliminary locus designation DOSLC3) and human chromosome 15, for clone pMS 1-27 (DOSLC2) and chromosome 20, and for clone pMS 1-37 (DOSLC1) and chromosome 3. Two independent hybrids had retained only the long arm of chromosome 3 and did not hybridize with this probe. Therefore, we assign this locus (now termed D3S3) to the short arm of chromosome 3.