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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Cosmids


High impact information on Cosmids

  • Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme, diadenosine 5', 5''' P1, P4-tetraphosphate asymmetrical hydrolase [5].
  • A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region [6].
  • We identified expressed sequences within a cosmid in the glycerol kinase (GK) "critical region" of Xp21 that had impressive similarity to prokaryotic GKs [7].
  • We have now isolated cosmids for six additional human PAX genes (PAX-1,-2,-5,-7,-8,-9) and a polymerase chain reaction fragment for PAX-4 [8].
  • A 1.2-Megabase stretch of DNA from the short arm of chromosome 6 containing the SCA1 locus was isolated in a yeast artificial chromosome contig and subcloned into cosmids [9].

Chemical compound and disease context of Cosmids


Biological context of Cosmids

  • A total of 116,118 basepairs (bp) derived from three cosmids spanning the ERCC1 locus of human chromosome 19q13.3 have been sequenced with automated fluorescence-based sequencers and analysed by polymerase chain reaction amplification and computer methods [15].
  • To identify the K10 gene we used P-mediated transformation with cosmid clones constructed in cos-P, a cosmid vector incorporating the terminal repeats of the P element [16].
  • A DNA probe from a human Y chromosome-derived cosmid detects a single-copy genomic DNA fragment which can appear in different allelic forms shared by both sex chromosomes [17].
  • A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor [18].
  • In contrast, C2 RNA and protein were expressed by L cells alone and by L cells transfected with a control plasmid, as well as by L cells transfected with cosmids encoding human and murine complement genes [19].

Anatomical context of Cosmids

  • Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs [20].
  • Furthermore, in a murine fibroblast L-cell line transfected with cosmid DNA bearing the human C2 and factor B genes, IL-1 mediated a reversible dose- and time-dependent increase in factor B expression in the transfected cells [21].
  • To explore the mechanism of constitutive IL-2 expression in MLA 144, we have isolated and characterized cosmid clones representing a normal and a doubly inserted IL-2 allele in this cell line [22].
  • The cosmids mapped to 16p13.13-p13.2, the location assigned to ERCC4 by using somatic cell hybrids [23].
  • We have recently isolated overlapping recombinant cosmids that represent the equivalent of two complete dihydrofolate reductase (dhfr) amplicon types from the methotrexate-resistant Chinese hamster ovary (CHO) cell line CHOC 400 [24].

Associations of Cosmids with chemical compounds

  • The genes were cloned in a cosmid vector and the entire cosmid was nick translated to incorporate biotin-labeled dUTP [25].
  • Due to the original linkage of the oncogene with the cosmid containing the kanamycin resistance gene, a series of kanamycin-resistant cosmids were isolated, five of which contained an active oncogene [26].
  • Mouse Lewis Lung tumor DNA was ligated to a cosmid containing a geneticin (G418)/kanamycin resistance gene and transferred into NIH3T3 cells [26].
  • A cloned genomic fragment containing the single C4B gene was isolated and found to be similar to the homologous region of a cosmid from a normal individual carrying a C4A gene [27].
  • Simultaneous hybridization of the biotinylated long interspersed element probe and a digoxigenin-labeled cosmid to metaphase spreads allows rapid localization of a probe of interest to a particular cytogenetic band on a chromosome [28].

Gene context of Cosmids

  • By subcloning a YAC with a 640 kilobases (kb) insert which spans the DXS7-MAOB interval we have generated a cosmid contig which extends 250 kb beyond the MAOB gene [29].
  • However, by mapping of 56.8 kb of overlapping cosmid clones and direct sequencing, we could localize the polymorphic NcoI restriction site within the first intron of the TNF-beta gene and not in the TNF-alpha gene [30].
  • The 190 kb of DNA linking all five CD1 genes has been spanned by 14 overlapping cosmids [31].
  • 3. Direct transfer of a cosmid bearing the ERCC2 gene conferred UV resistance to XP-D cells [32].
  • Six of these, with deletions <500 kb, share a similar proximal breakpoint within a cosmid containing the last 10 exons of PAX6 and part of the neighboring gene, ELP4 [33].

Analytical, diagnostic and therapeutic context of Cosmids


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  2. Expression and rescuing of a cloned human tumour necrosis factor gene using an EBV-based shuttle cosmid vector. Kioussis, D., Wilson, F., Daniels, C., Leveton, C., Taverne, J., Playfair, J.H. EMBO J. (1987) [Pubmed]
  3. Molecular cloning and characterization of a mammalian excision repair gene that partially restores UV resistance to xeroderma pigmentosum complementation group D cells. Arrand, J.E., Bone, N.M., Johnson, R.T. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  4. Isolation of a new DNA marker in linkage disequilibrium with cystic fibrosis, situated between J3.11 (D7S8) and IRP. Estivill, X., McLean, C., Nunes, V., Casals, T., Gallano, P., Scambler, P., Williamson, R. Am. J. Hum. Genet. (1989) [Pubmed]
  5. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Ohta, M., Inoue, H., Cotticelli, M.G., Kastury, K., Baffa, R., Palazzo, J., Siprashvili, Z., Mori, M., McCue, P., Druck, T., Croce, C.M., Huebner, K. Cell (1996) [Pubmed]
  6. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Hahn, H., Wicking, C., Zaphiropoulous, P.G., Gailani, M.R., Shanley, S., Chidambaram, A., Vorechovsky, I., Holmberg, E., Unden, A.B., Gillies, S., Negus, K., Smyth, I., Pressman, C., Leffell, D.J., Gerrard, B., Goldstein, A.M., Dean, M., Toftgard, R., Chenevix-Trench, G., Wainwright, B., Bale, A.E. Cell (1996) [Pubmed]
  7. Genomic scanning for expressed sequences in Xp21 identifies the glycerol kinase gene. Guo, W., Worley, K., Adams, V., Mason, J., Sylvester-Jackson, D., Zhang, Y.H., Towbin, J.A., Fogt, D.D., Madu, S., Wheeler, D.A. Nat. Genet. (1993) [Pubmed]
  8. Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. Stapleton, P., Weith, A., Urbánek, P., Kozmik, Z., Busslinger, M. Nat. Genet. (1993) [Pubmed]
  9. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Orr, H.T., Chung, M.Y., Banfi, S., Kwiatkowski, T.J., Servadio, A., Beaudet, A.L., McCall, A.E., Duvick, L.A., Ranum, L.P., Zoghbi, H.Y. Nat. Genet. (1993) [Pubmed]
  10. The mouse Thy-1.2 glycoprotein gene: complete sequence and identification of an unusual promoter. Ingraham, H.A., Lawless, G.M., Evans, G.A. J. Immunol. (1986) [Pubmed]
  11. Presence in the 'silent' terminus region of the Escherichia coli K12 chromosome of cryptic gene(s) encoding a new nitrate reductase. Bonnefoy, V., Burini, J.F., Giordano, G., Pascal, M.C., Chippaux, M. Mol. Microbiol. (1987) [Pubmed]
  12. Biosynthesis of carbapenem antibiotic and prodigiosin pigment in Serratia is under quorum sensing control. Thomson, N.R., Crow, M.A., McGowan, S.J., Cox, A., Salmond, G.P. Mol. Microbiol. (2000) [Pubmed]
  13. Genetic analysis of the Erwinia chrysanthemi 3937 chrysobactin iron-transport system: characterization of a gene cluster involved in uptake and biosynthetic pathways. Franza, T., Enard, C., van Gijsegem, F., Expert, D. Mol. Microbiol. (1991) [Pubmed]
  14. Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin. Blanco, G., Patallo, E.P., Braña, A.F., Trefzer, A., Bechthold, A., Rohr, J., Méndez, C., Salas, J.A. Chem. Biol. (2001) [Pubmed]
  15. Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. Martin-Gallardo, A., McCombie, W.R., Gocayne, J.D., FitzGerald, M.G., Wallace, S., Lee, B.M., Lamerdin, J., Trapp, S., Kelley, J.M., Liu, L.I. Nat. Genet. (1992) [Pubmed]
  16. A 43 kilobase cosmid P transposon rescues the fs(1)K10 morphogenetic locus and three adjacent Drosophila developmental mutants. Haenlin, M., Steller, H., Pirrotta, V., Mohier, E. Cell (1985) [Pubmed]
  17. Pseudoautosomal DNA sequences in the pairing region of the human sex chromosomes. Simmler, M.C., Rouyer, F., Vergnaud, G., Nyström-Lahti, M., Ngo, K.Y., de la Chapelle, A., Weissenbach, J. Nature (1985) [Pubmed]
  18. Gene transfer and molecular cloning of the human NGF receptor. Chao, M.V., Bothwell, M.A., Ross, A.H., Koprowski, H., Lanahan, A.A., Buck, C.R., Sehgal, A. Science (1986) [Pubmed]
  19. Expression of complement proteins C2 and factor B in transfected L cells. Perlmutter, D.H., Colten, H.R., Grossberger, D., Strominger, J., Seidman, J.G., Chaplin, D.D. J. Clin. Invest. (1985) [Pubmed]
  20. Cloning of the alpha-adducin gene from the Huntington's disease candidate region of chromosome 4 by exon amplification. Taylor, S.A., Snell, R.G., Buckler, A., Ambrose, C., Duyao, M., Church, D., Lin, C.S., Altherr, M., Bates, G.P., Groot, N. Nat. Genet. (1992) [Pubmed]
  21. Regulation of class III major histocompatibility complex gene products by interleukin-1. Perlmutter, D.H., Goldberger, G., Dinarello, C.A., Mizel, S.B., Colten, H.R. Science (1986) [Pubmed]
  22. Retroviral activation of interleukin 2 gene in a gibbon ape T cell lymphoma line. Durand, D.B., Kamoun, M., Norris, C.A., Holbrook, N.J., Greengard, J.S., Crabtree, G.R., Kant, J.A. J. Exp. Med. (1986) [Pubmed]
  23. Molecular cloning of the human nucleotide-excision-repair gene ERCC4. Thompson, L.H., Brookman, K.W., Weber, C.A., Salazar, E.P., Reardon, J.T., Sancar, A., Deng, Z., Siciliano, M.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  24. Organization and genesis of dihydrofolate reductase amplicons in the genome of a methotrexate-resistant Chinese hamster ovary cell line. Ma, C., Looney, J.E., Leu, T.H., Hamlin, J.L. Mol. Cell. Biol. (1988) [Pubmed]
  25. Mapping muscle protein genes by in situ hybridization using biotin-labeled probes. Albertson, D.G. EMBO J. (1985) [Pubmed]
  26. Use of gene transfer and a novel cosmid rescue strategy to isolate transforming sequences. Brady, G., Funk, A., Mattern, J., Schütz, G., Brown, R. EMBO J. (1985) [Pubmed]
  27. Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region. Carroll, M.C., Palsdottir, A., Belt, K.T., Porter, R.R. EMBO J. (1985) [Pubmed]
  28. Differential distribution of long and short interspersed element sequences in the mouse genome: chromosome karyotyping by fluorescence in situ hybridization. Boyle, A.L., Ballard, S.G., Ward, D.C. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  29. Isolation of a candidate gene for Norrie disease by positional cloning. Berger, W., Meindl, A., van de Pol, T.J., Cremers, F.P., Ropers, H.H., Döerner, C., Monaco, A., Bergen, A.A., Lebo, R., Warburg, M. Nat. Genet. (1992) [Pubmed]
  30. Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. Messer, G., Spengler, U., Jung, M.C., Honold, G., Blömer, K., Pape, G.R., Riethmüller, G., Weiss, E.H. J. Exp. Med. (1991) [Pubmed]
  31. A physical map linking the five CD1 human thymocyte differentiation antigen genes. Yu, C.Y., Milstein, C. EMBO J. (1989) [Pubmed]
  32. Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene. Flejter, W.L., McDaniel, L.D., Johns, D., Friedberg, E.C., Schultz, R.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  33. Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia. Crolla, J.A., van Heyningen, V. Am. J. Hum. Genet. (2002) [Pubmed]
  34. Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin. Popko, B., Puckett, C., Lai, E., Shine, H.D., Readhead, C., Takahashi, N., Hunt, S.W., Sidman, R.L., Hood, L. Cell (1987) [Pubmed]
  35. Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly. Ledbetter, S.A., Kuwano, A., Dobyns, W.B., Ledbetter, D.H. Am. J. Hum. Genet. (1992) [Pubmed]
  36. Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome. Boultwood, J., Fidler, C., Lewis, S., MacCarthy, A., Sheridan, H., Kelly, S., Oscier, D., Buckle, V.J., Wainscoat, J.S. Blood (1993) [Pubmed]
  37. Molecular cloning, expression, and chromosomal localization of a human gene encoding the CD33 myeloid differentiation antigen. Peiper, S.C., Ashmun, R.A., Look, A.T. Blood (1988) [Pubmed]
  38. Cloning of a balanced translocation breakpoint in the DiGeorge syndrome critical region and isolation of a novel potential adhesion receptor gene in its vicinity. Demczuk, S., Aledo, R., Zucman, J., Delattre, O., Desmaze, C., Dauphinot, L., Jalbert, P., Rouleau, G.A., Thomas, G., Aurias, A. Hum. Mol. Genet. (1995) [Pubmed]
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