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Diminished support for linkage between manic depressive illness and X–chromosome markers in three Israeli pedigrees

Nature Genetics volume 3, pages 49–55 (1993)Cite this article

Abstract

The hypothesis that chromosomal region Xq27–28 harbours a gene for manicdepression has been a focus of interest in human genetics. X–linked inheritance of manic depressive illness has been re–examined in 3 multigeneration Israeli kindreds. Extension and re–evaluation of pedigree data, including new individuals, diagnostic follow–up, and analysis with DMA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP–F8–G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

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References

  1. Baron, M. et al. Genetic linkage between X-chromosome markers and bipolar affective illness. Nature 326, 289–292 (1987).

    Article  CAS  PubMed  Google Scholar 

  2. Baron, M. X-linkage and manic depressive illness: A reassessment. Soc. Biol. 38, 179–188 (1991).

    CAS  PubMed  Google Scholar 

  3. Winderickx, J. et al. Defective colour vision associated with a missence mutation in the human green visual pigment gene. Nature Genet. 1, 251–256 (1992).

    Article  CAS  PubMed  Google Scholar 

  4. Vulliamy, T.J. et al. Diverse point mutations in the human glucose-6-phosphate dehydrogenase gene cause enzyme deficiency and mild or severe hemolytic anemia. Proc. natn. Acad. Sci. U.S.A. 85, 5171–5175 (1988).

    Article  CAS  Google Scholar 

  5. Adler's Physiology of the Eye 7th edn (ed. Moses, R.A) (C.V. Mosby Co, St. Louis, 1981).

  6. Pokorny, J. & Smith, V.C. New observations concerning red-green color defects. Color Res. 7, 483–489 (1987).

    Google Scholar 

  7. Lohr, G.W. & Waller, H.D. In Methods of Enzymatic Analysis (ed. Bergmeyer, H.U.) 636 (Academic, New York, 1974).

    Book  Google Scholar 

  8. Berrettini, W.H. et al. X-Chromosome markers and manic depressive illness. Archs. gen. Psychiat. 47, 366–377 (1990).

    Article  CAS  Google Scholar 

  9. Gejman, P. et al. Manic depressive illness not linked to factor IX region in an independent series of pedigrees. Genomics 8, 648–655 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Van Broeckhoven, C. et al. Linkage analysis of families with manic depressive illness with markers from chromosome X and 11. Am. J. hum. Genet. 49, 54 (Suppl.) 362 (1991).

    Google Scholar 

  11. Mendlewicz, J. et al. Polymorphic DNA marker on X-chromosome and manic depression. Lancet i, 1230–1232 (1987).

    Article  Google Scholar 

  12. Gill, M., Castle, D. & Duggar, C. Cosegregation of Chrismas disease and major affective disorder in a pedigree. Brit. J. Psychiat. 160, 112–114 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Davies, K.E., Mandel, J-L, Monaco, A.P., Nussbaum, R.L. & Willard, H.F. Report of the committee on the sic constitution of the X chromosome. Cytogenet. Cell Genet. 58, 853–966 (1991).

    Article  Google Scholar 

  14. Egeland, J.A. et al. Bipolar affective disorder linked to DNA markers on chromosome 11. Nature 325, 783–787 (1987).

    Article  CAS  PubMed  Google Scholar 

  15. Kelsoe, J.R. et al. Reevaluation of the linkage relationship between chromosome 11 p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature 342, 238–243 (1989).

    Article  CAS  PubMed  Google Scholar 

  16. Baron, M., Endicott, J. & Ott, J. Genetic linkage in mental illness: Limitations and prospects. Brit. J. Psychiat. 157, 645–655 (1990).

    Article  CAS  PubMed  Google Scholar 

  17. Feldman, E. Bipolar pedigrees. Arch. gen. Psychiat. 48, 671 (1991).

    Article  Google Scholar 

  18. Hebebrand, J. A critical appraisal of X-linked bipolar illness. Br. J. Psychiat. 160, 7–11 (1992).

    Article  CAS  Google Scholar 

  19. Winokur, G. & Crowe, R.R. Bipolar pedigrees. Arch. gen. Psychiat. 48, 671 (1991).

    Article  Google Scholar 

  20. Baron, M. Bipolar pedigrees. Arch. gen. Psychiat. 48, 671–673 (1991).

    Article  Google Scholar 

  21. Buckle, V.J. et al. Chromosomal localization of GABA receptor subunit genes: relationship to human genetic disease. Neuron 3, 645–654 (1989).

    Article  Google Scholar 

  22. Bell, M.V. et al. Physical linkage of a QABA receptor subunit gene to the DXS374 locus in human Xq28. Am. J. hum. Genet. 45, 883–888 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kurdi-Haidar, B. et al. Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East. Am. J. hum. Genet. 47, 1013–1019 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Risch, N. A note on multiple testing procedures in linkage analysis. Am. J. hum. Genet. 48, 1058–1064 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Poustka, A. et al. Physical map of human Xq27-qter: Localizing the region of the fragile X mutation. Proc. natn. Acad. Sci U.S.A. 88, 8302–8306, 1991.

    Article  CAS  Google Scholar 

  26. Risch, N. & Giuffra, L. Model misspecification and multipoint linkage analysis. Hum. Hered. 42, 77–92 (1992).

    Article  CAS  PubMed  Google Scholar 

  27. Ott, J. Analysis of Human Genetic Linkage, revised edn (Johns Hopkins University Press, Baltimore, 1991).

  28. Hodge, S.E. & Greenberg, D.E. Sensitivity of lod scores to changes in diagnostic status. Am. J. hum. Genet. 50, 1053–1066 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Endicott, J. & Spitzer, R.L. A diagnostic interview: the schedule for Affective Disorders and Schizophrenia. Archs. gen. Psychiat. 35, 837–862 (1978).

    Article  CAS  Google Scholar 

  30. Andreasen, N.C., Endicott, J., Spitzer, R.L. & Winokur, G. The family history method using diagnostic criteria: reliability and validity. Archs. gen. Psychiat. 34, 1229–1235 (1977).

    Article  CAS  Google Scholar 

  31. Spitzer, R.L., Endicott, J. & Robins, E. Research diagnostic criteria: rationale and reliability. Archs. gen Psychiat. 35, 773–779 (1978).

    Article  CAS  Google Scholar 

  32. Anderson, M.A. & Gusella, J.F. Use of cyclosporin A in establishing Epstein-Barr virus - tranformed human lymphoblastoid cell lines. In Vitro 20, 856–858 (1984).

    Article  CAS  PubMed  Google Scholar 

  33. Gilliam, T.C. et al. Isolation of polymorphic DNA fragments from human chromosome 4. Nucl. Acids Res. 15, 1445–1458 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Feinberg, A.P. & Vogelstein, B. A technique for radiolabeling restriction endonuclease fragments to high specific activity. Analytic Biochem. 137, 266–267 (1984).

    Article  CAS  Google Scholar 

  35. Bernstein, R.E. Rapid screening dye test for detection of glucose-6-phosphate dehydrogenase deficiency in red cells. Nature 194, 192 (1962).

    Article  CAS  PubMed  Google Scholar 

  36. Lange, K., Weeks, D. & Boehnke, M. Programs for pedigree analysis: MENDEL, FISHER, and d GENE. Genet. Epidemiol. 5, 471–472 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Weeks, D.E., Ott, J., Lathrop, G.M. SLINK: a general simulation program for linkage analysis. Am. J. hum. Genet. 47, A204 (1990).

    Google Scholar 

  38. Feil, R., Aubourg, R., Heilig, R. & Mandel, J.-L. A 195-kb cosmid walk encompassing the human Xq28 color vision pigment genes. Genomics 6, 367–373 (1990).

    Article  CAS  PubMed  Google Scholar 

  39. Hicks, A.A., Johnson, K.J., Barnard, E.A. & Darlison, M.G. Dinucleotide repeat polymorphism in the human X-linked GABA receptor alpha 3-subunit gene. Nucl. Acids Res. 19, 4016 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Author notes

  1. Nelson F. Freimer & Amy Peterson

    Present address: Langley Porter Psychiatric Institute and Department of Psychiatry, University of California at San Francisco, San Francisco, California, 94143, USA

Authors and Affiliations

  1. New York State Psychiatric Institute and Departments of Psychiatry and Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York, 10032, USA

    Miron Baron, Nelson F. Freimer, Richard E. Straub, Susha Asokan, Kamna Das, Amy Peterson, Jean Endicott, Jurg Ott & T. Conrad Gilliam

  2. Departments of Epidemiology and Public Health and of Genetics, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Neil Risch

  3. Department of Psychiatry, Hadassah–Hebrew University Medical Center, Jerusalem, 91120, Israel

    Bernard Lerer & Joyce R. Alexander

  4. Center for Human Genetics, Boston University Medical Center, Boston, Massachusetts, 02118, USA

    Jean Amos

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Baron, M., Freimer, N., Risch, N. et al. Diminished support for linkage between manic depressive illness and X–chromosome markers in three Israeli pedigrees. Nat Genet 3, 49–55 (1993). https://doi.org/10.1038/ng0193-49

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