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. 1993 Mar;52(3):478–490.

Schizophrenia-associated chromosome 11q21 translocation: Identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources

Judy M Fletcher, Kathryn Evans, David Baillie, Philip Byrd, Diane Hanratty, Suzanne Leach, Cecile Julier, John R Gosden, Walter Muir, David J Porteous, David St Clair, Veronica van Heyningen
PMCID: PMC1682173  PMID: 8383424

Abstract

Genetic linkage, molecular analysis, and in situ hybridization have identified TYR and D11S388 as markers flanking the chromosome 11 breakpoint in a large pedigree where a balanced translocation, t(1;11)(q43;q21), segregates with schizophrenia and related affective disorders. Somatic cell hybrids, separating the two translocation chromosomes from each other and from the normal homologues, have been produced with the aid of immunomagnetic sorting for chromosome 1– and chromosome 11–encoded cell-surface antigens. The genes for two of these antigens map on either side of the 11q breakpoint. Immunomagnetic bead sorting was also used to isolate two stable X-irradiation hybrids for each cell-surface antigen. Each hybrid carries only chromosome 11 fragments. Translocation and X-irradiation hybrids were analyzed, mainly by PCR, for the presence of 19 chromosome 11 and 4 chromosome 1 markers. Ten newly designed primers are reported. The X-irradiation hybrids were also studied cytogenetically, for human DNA content, by in situ Cot1 DNA hybridization and by painting the Alu-PCR products from these four lines back onto normal human metaphases. The generation of the translocation hybrids and of the chromosome 11q fragment hybrids is a necessary preliminary to determining whether a schizophrenia-predisposition gene SCZD2 is encoded at this site.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews P. W., Knowles B. B., Parkar M., Pym B., Stanley K., Goodfellow P. N. A human cell-surface antigen defined by a monoclonal antibody and controlled by a gene on human chromosome 1. Ann Hum Genet. 1985 Jan;49(Pt 1):31–39. doi: 10.1111/j.1469-1809.1985.tb01673.x. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Baumann I., Stein B., Delius H., Rahmsdorf H. J., Herrlich P. 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region. Mol Cell Biol. 1987 Jun;7(6):2256–2266. doi: 10.1128/mcb.7.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barton C. H., Mann D. A., Walsh F. S. Characterization of the human N-CAM promoter. Biochem J. 1990 May 15;268(1):161–168. doi: 10.1042/bj2680161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breen M., Arveiler B., Murray I., Gosden J. R., Porteous D. J. YAC mapping by FISH using Alu-PCR-generated probes. Genomics. 1992 Jul;13(3):726–730. doi: 10.1016/0888-7543(92)90148-l. [DOI] [PubMed] [Google Scholar]
  5. Brookes A. J., Porteous D. J. Coincident sequence cloning: a new approach to genome analysis. Trends Biotechnol. 1992 Jan-Feb;10(1-2):40–44. doi: 10.1016/0167-7799(92)90166-s. [DOI] [PubMed] [Google Scholar]
  6. Clarke D. J., Buckley M. E. Familial association of albinism and schizophrenia. Br J Psychiatry. 1989 Oct;155:551–553. doi: 10.1192/bjp.155.4.551. [DOI] [PubMed] [Google Scholar]
  7. Cotter F., Nasipuri S., Lam G., Young B. D. Gene mapping by enzymatic amplification from flow-sorted chromosomes. Genomics. 1989 Oct;5(3):470–474. doi: 10.1016/0888-7543(89)90011-6. [DOI] [PubMed] [Google Scholar]
  8. Cowell I. G., Dixon K. H., Pemble S. E., Ketterer B., Taylor J. B. The structure of the human glutathione S-transferase pi gene. Biochem J. 1988 Oct 1;255(1):79–83. doi: 10.1042/bj2550079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dorin J. R., Emslie E., Hanratty D., Farrall M., Gosden J., Porteous D. J. Gene targeting for somatic cell manipulation: rapid analysis of reduced chromosome hybrids by Alu-PCR fingerprinting and chromosome painting. Hum Mol Genet. 1992 Apr;1(1):53–59. doi: 10.1093/hmg/1.1.53. [DOI] [PubMed] [Google Scholar]
  10. Giebel L. B., Spritz R. A. RFLP for MboI in the human tyrosinase (TYR) gene detected by PCR. Nucleic Acids Res. 1990 May 25;18(10):3103–3103. doi: 10.1093/nar/18.10.3103-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giebel L. B., Strunk K. M., Spritz R. A. Organization and nucleotide sequences of the human tyrosinase gene and a truncated tyrosinase-related segment. Genomics. 1991 Mar;9(3):435–445. doi: 10.1016/0888-7543(91)90409-8. [DOI] [PubMed] [Google Scholar]
  12. Goodfellow P. N., Banting G., Wiles M. V., Tunnacliffe A., Parkar M., Solomon E., Dalchau R., Fabre J. W. The gene, MIC4, which controls expression of the antigen defined by monoclonal antibody F10.44.2, is on human chromosome 11. Eur J Immunol. 1982 Aug;12(8):659–663. doi: 10.1002/eji.1830120807. [DOI] [PubMed] [Google Scholar]
  13. Gottesdiener K. M., Karpinski B. A., Lindsten T., Strominger J. L., Jones N. H., Thompson C. B., Leiden J. M. Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation. Mol Cell Biol. 1988 Sep;8(9):3809–3819. doi: 10.1128/mcb.8.9.3809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grandy D. K., Litt M., Allen L., Bunzow J. R., Marchionni M., Makam H., Reed L., Magenis R. E., Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. Am J Hum Genet. 1989 Nov;45(5):778–785. [PMC free article] [PubMed] [Google Scholar]
  15. Holland T., Gosden C. A balanced chromosomal translocation partially co-segregating with psychotic illness in a family. Psychiatry Res. 1990 Apr;32(1):1–8. doi: 10.1016/0165-1781(90)90129-s. [DOI] [PubMed] [Google Scholar]
  16. Janson M., Larsson C., Werelius B., Jones C., Glaser T., Nakamura Y., Jones C. P., Nordenskjöld M. Detailed physical map of human chromosomal region 11q12-13 shows high meiotic recombination rate around the MEN1 locus. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10609–10613. doi: 10.1073/pnas.88.23.10609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jeffreys A. J., Wilson V., Neumann R., Keyte J. Amplification of human minisatellites by the polymerase chain reaction: towards DNA fingerprinting of single cells. Nucleic Acids Res. 1988 Dec 9;16(23):10953–10971. doi: 10.1093/nar/16.23.10953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones C., Bill J., Larizza L., Pym B., Goodfellow P., Tunnacliffe A. Relationships between genes on human chromosome 11 encoding cell-surface antigens. Somat Cell Mol Genet. 1984 Jul;10(4):423–428. doi: 10.1007/BF01535638. [DOI] [PubMed] [Google Scholar]
  19. Julier C., Nakamura Y., Lathrop M., O'Connell P., Leppert M., Litt M., Mohandas T., Lalouel J. M., White R. A detailed genetic map of the long arm of chromosome 11. Genomics. 1990 Jul;7(3):335–345. doi: 10.1016/0888-7543(90)90167-s. [DOI] [PubMed] [Google Scholar]
  20. Klebe R. J., Chen T., Ruddle F. H. Controlled production of proliferating somatic cell hybrids. J Cell Biol. 1970 Apr;45(1):74–82. doi: 10.1083/jcb.45.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Koeffler H. P., Sparkes R. S., Stang H., Mohandas T. Regional assignment of genes for human alpha-globin and phosphoglycollate phosphatase to the short arm of chromosome 16. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7015–7018. doi: 10.1073/pnas.78.11.7015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lewis W. H., Yeger H., Bonetta L., Chan H. S., Kang J., Junien C., Cowell J., Jones C., Dafoe L. A. Homozygous deletion of a DNA marker from chromosome 11p13 in sporadic Wilms tumor. Genomics. 1988 Jul;3(1):25–31. doi: 10.1016/0888-7543(88)90154-1. [DOI] [PubMed] [Google Scholar]
  23. Litt M., Sharma V., Luty J. A. Dinucleotide repeat polymorphism at the D11S35 locus. Nucleic Acids Res. 1990 Oct 11;18(19):5921–5921. doi: 10.1093/nar/18.19.5921-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McConville C. M., Formstone C. J., Hernandez D., Thick J., Taylor A. M. Fine mapping of the chromosome 11q22-23 region using PFGE, linkage and haplotype analysis; localization of the gene for ataxia telangiectasia to a 5cM region flanked by NCAM/DRD2 and STMY/CJ52.75, phi 2.22. Nucleic Acids Res. 1990 Aug 11;18(15):4335–4343. doi: 10.1093/nar/18.15.4335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mohandas T., Sparkes R. S., Hellkuhl B., Grzeschik K. H., Shapiro L. J. Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6759–6763. doi: 10.1073/pnas.77.11.6759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morris S. W., Muir W., St Clair D. Dinucleotide repeat polymorphism at the human tyrosinase gene. Nucleic Acids Res. 1991 Dec 25;19(24):6968–6968. doi: 10.1093/nar/19.24.6968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakamura Y., Holm T., White R. Isolation and mapping of a polymorphic DNA sequence (pTHH33) on chromosome 1q [D1S81]. Nucleic Acids Res. 1988 Oct 11;16(19):9363–9363. doi: 10.1093/nar/16.19.9363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Porteous D. J., Bickmore W., Christie S., Boyd P. A., Cranston G., Fletcher J. M., Gosden J. R., Rout D., Seawright A., Simola K. O. HRAS1-selected chromosome transfer generates markers that colocalize aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms tumor gene within band 11p13. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5355–5359. doi: 10.1073/pnas.84.15.5355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Porteous D. J., Morten J. E., Cranston G., Fletcher J. M., Mitchell A., van Heyningen V., Fantes J. A., Boyd P. A., Hastie N. D. Molecular and physical arrangements of human DNA in HRAS1-selected, chromosome-mediated transfectants. Mol Cell Biol. 1986 Jun;6(6):2223–2232. doi: 10.1128/mcb.6.6.2223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Royle N. J., Clarkson R. E., Wong Z., Jeffreys A. J. Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. Genomics. 1988 Nov;3(4):352–360. doi: 10.1016/0888-7543(88)90127-9. [DOI] [PubMed] [Google Scholar]
  32. Seawright A., Fletcher J. M., Fantes J. A., Morrison H., Porteous D. J., Li S. S., Hastie N. D., Van Heyningen V. Analysis of WAGR deletions and related translocations with gene-specific DNA probes, using FACS-selected cell hybrids. Somat Cell Mol Genet. 1988 Jan;14(1):21–30. doi: 10.1007/BF01535046. [DOI] [PubMed] [Google Scholar]
  33. Seeman P., Niznik H. B., Guan H. C., Booth G., Ulpian C. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10156–10160. doi: 10.1073/pnas.86.24.10156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  35. Sirum K. L., Brinckerhoff C. E. Cloning of the genes for human stromelysin and stromelysin 2: differential expression in rheumatoid synovial fibroblasts. Biochemistry. 1989 Oct 31;28(22):8691–8698. doi: 10.1021/bi00448a004. [DOI] [PubMed] [Google Scholar]
  36. Spritz R. A., Strunk K. M., Giebel L. B., King R. A. Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. N Engl J Med. 1990 Jun 14;322(24):1724–1728. doi: 10.1056/NEJM199006143222407. [DOI] [PubMed] [Google Scholar]
  37. St Clair D., Blackwood D., Muir W., Carothers A., Walker M., Spowart G., Gosden C., Evans H. J. Association within a family of a balanced autosomal translocation with major mental illness. Lancet. 1990 Jul 7;336(8706):13–16. doi: 10.1016/0140-6736(90)91520-k. [DOI] [PubMed] [Google Scholar]
  38. Tanigami A., Tokino T., Takiguchi S., Mori M., Glaser T., Park J. W., Jones C., Nakamura Y. Mapping of 262 DNA markers into 24 intervals on human chromosome 11. Am J Hum Genet. 1992 Jan;50(1):56–64. [PMC free article] [PubMed] [Google Scholar]
  39. Theune S., Fung J., Todd S., Sakaguchi A. Y., Naylor S. L. PCR primers for human chromosomes: reagents for the rapid analysis of somatic cell hybrids. Genomics. 1991 Mar;9(3):511–516. doi: 10.1016/0888-7543(91)90418-e. [DOI] [PubMed] [Google Scholar]
  40. Weber J. L., Kwitek A. E., May P. E. Dinucleotide repeat polymorphism at the D1S102 locus. Nucleic Acids Res. 1990 Apr 25;18(8):2199–2199. [PMC free article] [PubMed] [Google Scholar]
  41. Westerveld A., Visser R. P., Meera Khan P., Bootsma D. Loss of human genetic markers in man--Chinese hamster somatic cell hybrids. Nat New Biol. 1971 Nov 3;234(44):20–24. doi: 10.1038/newbio234020a0. [DOI] [PubMed] [Google Scholar]
  42. Woodroofe M. N., Tunnacliffe A., Pym B., Goodfellow P. N., Walsh F. S. Human muscle cell surface antigen 16.3A5 is encoded by a gene on chromosome 11. Somat Cell Mol Genet. 1984 Sep;10(5):535–540. doi: 10.1007/BF01534858. [DOI] [PubMed] [Google Scholar]
  43. Yoshida T., Miyagawa K., Odagiri H., Sakamoto H., Little P. F., Terada M., Sugimura T. Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7305–7309. doi: 10.1073/pnas.84.20.7305. [DOI] [PMC free article] [PubMed] [Google Scholar]

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