Gene linkage in man and Chinese hamster studied in somatic cell hybrids

Genetic studies of higher organisms, including man, are based on the analysis of segregation and recombination events resulting from se>.."Ual reproduction. In 1962 Pontecorvo predicted, however, that cultured cells could also be employed for this purpose. He suggested that parase::\"Ual events, detected in certain fungi, might occur also in 11in vitro11 cultured cells. Now, ten years later, there are strong indications that this prediction will indeed come true

On General Axial Gauges for QCD

General Axial Gauges within a perturbative approach to QCD are plagued by 'spurious' propagator singularities. Their regularisation has to face major conceptual and technical problems. We show that this obstacle is naturally absent within a Wilsonian or 'Exact' Renormalisation Group approach and explain why this is so. The axial gauge turns out to be a fixed point under the flow, and the universal 1-loop running of the gauge coupling is computed.Comment: 4 pages, latex, talk presented by DFL at QCD'98, Montpellier, July 2-8, 1998; to be published in Nucl. Phys. B (Proc. Suppl.

New distal marker closely linked to the fragile X locus

We have isolated II-10, a new X-chromosomal probe that identifies a highly informative two-allele TaqI restriction fragment length polymorphism at locus DXS466. Using somatic cell hybrids containing distinct portions of the long arm of the X chromosome, we could localize DXS466 between DXS296 and DXS304, both of which are closely linked distal markers for fragile X. This regional localization was supported by the analysis, in fragile X families, of recombination events between these three loci, the fragile X locus and locus DXS52, the latter being located at a more distal position. DXS466 is closely linked to the fragile X locus with a peak lod score of 7.79 at a recombination fraction of 0.02. Heterozygosity of DXS466 is approximately 50%. Its close proximity and relatively high informativity make DXS466 a valuable new diagnostic DNA marker for fragile X

Genomic characterization of the human DNA excision repair gene ERCC-1.

In this report the genomic characterization of the human excision repair gene ERCC-1 is presented. The gene consists of 10 exons spread over approximately 15 kb. By means of a transfection assay the ERCC-1 promoter was confined to a region of + 170 bp upstream of the transcriptional start site. Classical promoter elements like CAAT, TATA and GC-boxes are absent from this region. Furthermore, ERCC-1 transcription is not UV-inducible. A possible explanation is provided for the previously reported alternative splicing of exon VIII. Analysis of ERCC-1 cDNA clones revealed the occurrence of differential polyadenylation which gives ERCC-1 transcripts of 3.4 and 3.8 kb in addition to the major 1.1 kb mRNA. Apparent evolutionary conservation of differential polyadenylation of ERCC-1 transcripts suggests a possible role for this mode of RNA processing in the ERCC-1 repair function

Evolution and mutagenesis of the mammalian excision repair gene ERCC-1

The human DNA excision repair protein ERCC-1 exhibits homology to the yeast RADIO repair protein and its longer C-terminus displays similarity to parts of the E.coli repair proteins uvrA and uvrC. To study the evolution of this 'mosaic' ERCC-1 gene we have isolated the mouse homologue. Mouse ERCC-1 harbors the same pattern of homology with RAD10 and has a comparable C-terminal extension as its human equivalent. Mutation studies show that the strongly conserved C-terminus is essential in contrast to the less conserved N-terminus which is even dispensible. The mouse ERCC-1 amino acid sequence is compatible with a previously postulated nuclear location signal and DNA-binding domain. The ERCC-1 promoter harbors a region which is highly conserved in mouse and man. Since the ERCC-1 promoter is devoid of all classical promoter elements this region may be responsible for the low constitutive level of expression in all mouse tissues and stages of embryogenesis examined

Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and aminoacid homology with the yeast DNA repair gene RAD10.

The human excision repair gene ERCC-7 was cloned after DNA mediated gene transfer to the CHO mutant 43-38, which is sensitive to ultraviolet light and mitomycin-C. We describe the cloning and sequence analysis of the ERCC-7 cDNA and partial characterization of the gene. ERCC.1 has a size of 15 kb and is located on human chromosome 19. The ERCC.1 precursor RNA is subject to alternative splicing of an internal 72 bp coding exon. Only the cDNA of the larger 1.1 kb transcript, encoding a protein of 297 amino acids, was able to confer resistance to ultraviolet light and mitomycin-C on 43-38 cells. Significant amino acid sequence homology was found between the ERCC.7 gene product and the yeast excision repair protein RADIO. The most homologous region displayed structural homology with DNA binding domains of various polypeptides

Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

Background. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic value. Methods. We used Southern blot analysis to study the allelic loss of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 17q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells. Results. Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outcomes. In a multivariate analysis, loss of chromosome 1p was the most powerful prognostic factor. It provided strong prognostic information when it was included in multivariate models containing the prognostic factors of age and stage or serum ferritin level and stage. Among the patients with stage I, II, or IVS disease, the mean (±SD) three-year event-free survival was 100 percent in those without allelic loss of chromosome 1p and 34±15 percent in those with such loss; the rates of three- year event-free survival among the patients with stage III and stage IV disease were 53±10 percent and 0 percent, respectively. Conclusions. The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It reliably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be considered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk

Amplification of the anonymous marker D17S67 in malignant astrocytomas

Loss of heterozygosity (LOH) for chromosome arms 9p, 10p, 10q, and 17p and amplification of the epidermal growth factor receptor (EGFR) gene have been identified as frequent genetic changes in malignant astrocytomas. We have found amplification of the anonymous marker D17S67 on chromosome arm 17p in 10% (3 of 30 cases) of astrocytomas of the highest malignancy grade. The tumors with D17S67 amplification displayed other genetic changes on chromosome 17, including additional amplifications and deletions. All three patients with D17S67 amplification developed severe brain edema and died within I month after operation. Genes Chrom Cancer 9:148‐152 (1994). © 1994 Wiley‐Liss, Inc

Goed gekeurd : aanstellingskeuringenbeleid en de invulling en uitvoering van de Wet op de medische keuringen

Dit rapport bevat de resultaten van het eerste deelonderzoek naar de uitvoering van het onderdeel aanstellingskeuringen van de Wet op de medische keuringen (WMK). Dat betekent dat hier met name de wetstechnische aspecten van de WMK en de uitvoering daarvan worden besproken in relatie tot een sollicitatie naar en aanstelling in arbeid. De rechten van veel keurlingen zijn na de invoering van de WMK verbeterd, zij het langzaam. Hetzelfde kan worden gezegd van de nieuwe kwaliteitsnormen voor keuringsartsen en de inhoud van de keuring. Het aantal zinloze medische keuringen is drastisch gedaald, en de inhoud van de keuring door een arts is meer functiegericht geworden. Ook is de professionele zelfstandigheid van keuringsartsen verbeterd door de certificeringseisen die met betrekking tot de WMK zijn opgesteld voor arbodiensten. Een consequentie van functie-eis als uitgangspunt voor keuren, is dat de gezondheid van de sollicitant in relatie tot de uit te voeren werkzaamheden niet meegenomen wordt in de beoordeling voor wel of niet keuren