Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1990 Sep;47(3):524–535.

Exclusion of a schizophrenia susceptibility gene from the chromosome 5q11-q13 region: new data and a reanalysis of previous reports.

P McGuffin 1, M Sargeant 1, G Hetti 1, S Tidmarsh 1, S Whatley 1, R M Marchbanks 1
PMCID: PMC1683884  PMID: 2393025

Abstract

The report of a putative schizophrenia susceptibility gene linked to markers in the chromosome 5q11-q13 region and subsequent failures of replication have provoked considerable controversy. We here report six Welsh families multiply affected with schizophrenia in which there is no evidence for linkage between a dominant-like schizophrenia gene and 5q11-q13 markers. It is argued that our new results together with a combined reanalysis of previous studies suggest that a schizophrenia susceptibility gene can be excluded from the 5q11-q13 region. The apparent disparities between published results are most likely to reflect a chance finding in the one positive study and probably should not be interpreted as resulting from true linkage heterogeneity.

Full text

PDF

Selected References

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

  1. Andrew B., Watt D. C., Gillespie C., Chapel H. A study of genetic linkage in schizophrenia. Psychol Med. 1987 May;17(2):363–370. doi: 10.1017/s0033291700024910. [DOI] [PubMed] [Google Scholar]
  2. Bassett A. S., McGillivray B. C., Jones B. D., Pantzar J. T. Partial trisomy chromosome 5 cosegregating with schizophrenia. Lancet. 1988 Apr 9;1(8589):799–801. doi: 10.1016/s0140-6736(88)91660-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Botstein D., White R. L., Skolnick M., Davis R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed] [Google Scholar]
  4. Chadda R., Kulhara P., Singh T., Sehgal S. HLA antigens in schizophrenia: a family study. Br J Psychiatry. 1986 Nov;149:612–615. doi: 10.1192/bjp.149.5.612. [DOI] [PubMed] [Google Scholar]
  5. Detera-Wadleigh S. D., Goldin L. R., Sherrington R., Encio I., de Miguel C., Berrettini W., Gurling H., Gershon E. S. Exclusion of linkage to 5q11-13 in families with schizophrenia and other psychiatric disorders. Nature. 1989 Aug 3;340(6232):391–393. doi: 10.1038/340391a0. [DOI] [PubMed] [Google Scholar]
  6. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  7. Farmer A. E., McGuffin P., Gottesman I. I. Twin concordance for DSM-III schizophrenia. Scrutinizing the validity of the definition. Arch Gen Psychiatry. 1987 Jul;44(7):634–641. doi: 10.1001/archpsyc.1987.01800190054009. [DOI] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Goldin L. R., DeLisi L. E., Gershon E. S. Relationship of HLA to schizophrenia in 10 nuclear families. Psychiatry Res. 1987 Jan;20(1):69–77. doi: 10.1016/0165-1781(87)90124-7. [DOI] [PubMed] [Google Scholar]
  10. Kendler K. S., Gruenberg A. M., Strauss J. S. An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. II. The relationship between schizotypal personality disorder and schizophrenia. Arch Gen Psychiatry. 1981 Sep;38(9):982–984. doi: 10.1001/archpsyc.1981.01780340034003. [DOI] [PubMed] [Google Scholar]
  11. Kennedy J. L., Giuffra L. A., Moises H. W., Cavalli-Sforza L. L., Pakstis A. J., Kidd J. R., Castiglione C. M., Sjogren B., Wetterberg L., Kidd K. K. Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. Nature. 1988 Nov 10;336(6195):167–170. doi: 10.1038/336167a0. [DOI] [PubMed] [Google Scholar]
  12. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Leppert M., Dobbs M., Scambler P., O'Connell P., Nakamura Y., Stauffer D., Woodward S., Burt R., Hughes J., Gardner E. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987 Dec 4;238(4832):1411–1413. doi: 10.1126/science.3479843. [DOI] [PubMed] [Google Scholar]
  14. Litt M., White R. L. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. doi: 10.1073/pnas.82.18.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  16. McGue M., Gottesman I. I., Rao D. C. Resolving genetic models for the transmission of schizophrenia. Genet Epidemiol. 1985;2(1):99–110. doi: 10.1002/gepi.1370020110. [DOI] [PubMed] [Google Scholar]
  17. McGuffin P., Farmer A. E., Gottesman I. I., Murray R. M., Reveley A. M. Twin concordance for operationally defined schizophrenia. Confirmation of familiality and heritability. Arch Gen Psychiatry. 1984 Jun;41(6):541–545. doi: 10.1001/archpsyc.1984.01790170015002. [DOI] [PubMed] [Google Scholar]
  18. McGuffin P., Festenstein H., Murray R. A family study of HLA antigens and other genetic markers in schizophrenia. Psychol Med. 1983 Feb;13(1):31–43. doi: 10.1017/s0033291700050042. [DOI] [PubMed] [Google Scholar]
  19. McGuffin P., Katz R., Aldrich J. Past and present state examination: the assessment of 'lifetime ever' psychopathology. Psychol Med. 1986 May;16(2):461–465. doi: 10.1017/s0033291700009302. [DOI] [PubMed] [Google Scholar]
  20. McGuffin P. Major genes for major affective disorder? Br J Psychiatry. 1988 Nov;153:591–596. doi: 10.1192/bjp.153.5.591. [DOI] [PubMed] [Google Scholar]
  21. McGuffin P., Sturt E. Genetic markers in schizophrenia. Hum Hered. 1986;36(2):65–88. doi: 10.1159/000153604. [DOI] [PubMed] [Google Scholar]
  22. O'Rourke D. H., Gottesman I. I., Suarez B. K., Rice J., Reich T. Refutation of the general single-locus model for the etiology of schizophrenia. Am J Hum Genet. 1982 Jul;34(4):630–649. [PMC free article] [PubMed] [Google Scholar]
  23. SMITH C. A. TESTING FOR HETEROGENEITY OF RECOMBINATION FRACTION VALUES IN HUMAN GENETICS. Ann Hum Genet. 1963 Nov;27:175–182. doi: 10.1111/j.1469-1809.1963.tb00210.x. [DOI] [PubMed] [Google Scholar]
  24. Sherrington R., Brynjolfsson J., Petursson H., Potter M., Dudleston K., Barraclough B., Wasmuth J., Dobbs M., Gurling H. Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature. 1988 Nov 10;336(6195):164–167. doi: 10.1038/336164a0. [DOI] [PubMed] [Google Scholar]
  25. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  26. St Clair D., Blackwood D., Muir W., Baillie D., Hubbard A., Wright A., Evans H. J. No linkage of chromosome 5q11-q13 markers to schizophrenia in Scottish families. Nature. 1989 May 25;339(6222):305–309. doi: 10.1038/339305a0. [DOI] [PubMed] [Google Scholar]
  27. Sturt E., McGuffin P. Can linkage and marker association resolve the genetic aetiology of psychiatric disorders? Review and argument. Psychol Med. 1985 Aug;15(3):455–462. doi: 10.1017/s0033291700031330. [DOI] [PubMed] [Google Scholar]
  28. Svejgaard A., Platz P., Ryder L. P., Nielsen L. S., Thomsen M. HL-A and disease associations--a survey. Transplant Rev. 1975;22:3–43. doi: 10.1111/j.1600-065x.1975.tb01550.x. [DOI] [PubMed] [Google Scholar]
  29. Turner W. J. Genetic markers for schizotaxia. Biol Psychiatry. 1979 Feb;14(1):177–206. [PubMed] [Google Scholar]
  30. WIENER A. S. Blood-groups and disease. A critical review. Lancet. 1962 Apr 21;1(7234):813–816. doi: 10.1016/s0140-6736(62)91835-4. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES