The Molecular Genetics of Bipolar Disease

  • Wade H. Berrettini
Part of the The Depressive Illness Series book series (DISS, volume 3)


The development of molecular genetic techniques and relatively complete linkage maps of the human genome has led to the discovery of causative genes for inherited diseases of uncertain pathophysiology, including cystic fibrosis (Riordan et al., 1990), retinoblastoma (Friend et al., 1986), and familial osteoarthritis (Alla-Kokko et al., 1990). The chromosomal locations of genes for numerous other inherited diseases of unknown biochemical etiology have been defined, although the precise genes have not been discovered yet (for review see Human Gene Mapping 10, 1989).


Color Blindness Affective Illness Bipolar Disease Original Pedigree Affection Status Model 
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  1. Ala-Kokko L, Baldwin CT, Moskowitz RW, Prockop DJ: Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis chrondrodysplasia. Proc Nat Acad Sci (USA) 1990; 87: 6565–6568.Google Scholar
  2. Baron M: Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness. Arch Gen Psychiat 1977; 34: 721–725.PubMedCrossRefGoogle Scholar
  3. Baron M, Risch N, Hamburger R, Mandel B, Kushner S, Newman M, Drumer D, Belmaker RH: Genetic linkage between X-chromosome markers and bipolar effective illness. Nature 1987; 326: 289–292.PubMedCrossRefGoogle Scholar
  4. Bell MV, Bloomfield J, McKinley M, Patterson MN, Darlison MG, Barnard EA, Davies KE: Physical linkage of a GABA receptor subunit gene to the DXS374 locus in human Xq28. Am J Human Genet 1989; 45: 883–888.Google Scholar
  5. Berrettini WH, Goldin LR, Gelernter J, Gejman PV, Gershon ES, Detera-Wadleigh S: X-chromosome markers and manic-depressive illness: Rejection of linkage to Xq28 in nine bipolar pedigrees. Arch Gen Psychiat 1990; 47: 366–373.PubMedCrossRefGoogle Scholar
  6. Berrettini WH: Is investment in molecular genetics worthwhile? Biol Psychiat 1991; 30 (3): 213–215.PubMedCrossRefGoogle Scholar
  7. Berrettini WH, Detera-Wadleigh SD, Goldin LR, Martinez M, Hsieh W-T, Hoehe M, Choi H, Muniec D, Coffman D, Ferraro TN, Guroff JJ, Kazuba D, Harris N, Kron E, Nurnberger Jr JI, Alexander R, Gershon ES: Genomic screening for genes predisposing to bipolar disease. Psychiat Gen 1991; 2: 41–56.Google Scholar
  8. Byerley W, Mellon C: Mapping genes for manic-depression and schizophrenia with DNA markers. Trends Neurol Sci 1989; 12: 46–48.CrossRefGoogle Scholar
  9. Clerget-Carpoux F, Bonaiti-Pellie C, Hochez J: Effects of misspecifying genetic parameters in lod score analysis. Biometrics 1986; 42: 393–399.CrossRefGoogle Scholar
  10. Cox N, Reich R, Rice T, Elston R, Schober J, Keats B: Segregation and linkage analyses of bipolar and major depressive illnesses in multigenerational pedigrees. J Psychiat Res 1989; 23: 109–123.PubMedCrossRefGoogle Scholar
  11. Del Zompo M, Bochetta A, Goldin LR: Linkage between X-chromosome markers and manic-depressive illness: Two Sardinian pedigrees. Acta Psychiat Scand 1984; 70: 282–287.PubMedCrossRefGoogle Scholar
  12. Del Zompo M, Pedditzi M, Ruiu S, Goldin LR, Berrettini WH, Boccheta A:. Association and linkage studies of affective disorders. In: Racagni G, Brunello N, Fukuda T (Eds.), Biological Psychiatry (Vol. 2). Proceedings of the 5th World Congress of Biological Psychiatry, Florence, June 9–14, 1991. New York, Elsevier Science Publishing Co., 1991, pp 449–451.Google Scholar
  13. Detera-Wadleigh SD, Berrettini WH, Goldin LR, Boorman D, Anderson S, Gershon ES: Close linkage of c-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees. Nature 1987; 325: 806–808.PubMedCrossRefGoogle Scholar
  14. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE: Bipolar affective disorder linked to DNA markers on chromosome 11. Nature 1987; 325: 783–787.PubMedCrossRefGoogle Scholar
  15. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323: 643–646.PubMedCrossRefGoogle Scholar
  16. Gejman PV, Detera-Wadleigh S, Martinez MM, Berrettini WH, Goldin LR, Gelernter J, Hsieh WT, Gershon ES: Manic-depressive illness not linked to Factor IX in an independent series of pedigrees. Genomics 1990; 8: 648–655.PubMedCrossRefGoogle Scholar
  17. Gershon ES, Targum SD, Matthysee S, Bunney Jr, WE: Color blindness not closely linked to bipolar illness. Arch Gen Psychiat 1979; 36: 1423–1430.PubMedCrossRefGoogle Scholar
  18. Gershon ES, Hamovit J, Guroff JJ, Dibble E, Leckman JF, Sceery W, Targum SD, Nurnberger Jr, JI, Goldin LR, Bunney Jr, WE: A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control probands. Arch Gen Psychiat 1982; 39: 1157–1162.PubMedCrossRefGoogle Scholar
  19. Gershon ES, Merrill CR, Goldin LR, DeLisi LE, Berrettini WH, Nurnberger Jr, JI: The role of molecular genetics in psychiatry. Biol Psychiat 1987; 22: 1388–1405.PubMedCrossRefGoogle Scholar
  20. Gershon ES, Berrettini WH, Nurnberger Jr, JI, Goldin LR: Genetic studies of affective illness. In: Mann JJ (Ed.), Models of Depressive Disorders, New York: Plenum Press, 1989; 109–142.CrossRefGoogle Scholar
  21. Gershon ES: Marker genotyping errors in old data on X-linkage in bipolar illness. Biol Psychiat 1991; 29: 721–729.PubMedCrossRefGoogle Scholar
  22. Gill M, McKeon P, Humphries P: Linkage analysis of manic-depression in an Irish family using Hpras 1 and INS DNA markers. J Med Genet 1988; 25: 634–637.PubMedCrossRefGoogle Scholar
  23. Goate AM, Haynes AR, Owen MJ: Predisposing locus for AD on chromosome 21. Lancet 1989; is 352–355.Google Scholar
  24. Goldstein AM, Weeks DE, Cortessis V, Haile RW: Comparison of the affected pedigree member and lod score methods. In: Elston RC, Spence A, Hodge SE, MacCluer J (Eds.), Multipoint Mapping and Linkage Based Upon Affected Pedigree Members: Genetic Analysis Workshop 6, New York: Alan R. Liss, 1989, 135–140.Google Scholar
  25. Hodgkinson S, Sherrington R, Gurling HMD, Marchbanks RM, Reeders ST, Mallet J, Petursson H, Brynjolfsson J: Molecular evidence for heterogeneity in manic-depression. Nature 1987; 325: 805–807.PubMedCrossRefGoogle Scholar
  26. Human Gene Mapping 10: Tenth international workshop on human gene mapping (1989). Cytogenet Cell Genetics 1989; 51: 1–1147.CrossRefGoogle Scholar
  27. Kelsoe JR, Ginns EI, Egeland JA, Gerhard DS, Goldstein AM, Bale SJ, Pauls DL, Long RT, Kidd KK, Conte G, Housman DE, Paul SM: Reevaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature 1990; 342: 238–243.CrossRefGoogle Scholar
  28. Knowleton RG, Katzenstein PL, Moskowitz RW, Weaver EJ, Malemud CJ, Path-ria MN, Jimenez SA, Prockop DJ: Genetic linkage of a polymorphism in the type II procollagen gene (COL2A1) to primary osteoarthritis associated with mild chondrodysplasia. New Engl J Med 1990; 322: 525–530.Google Scholar
  29. Kunkel LM, Hejtmancik JF, Kaskey CT: Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 1986; 322: 73–77.PubMedCrossRefGoogle Scholar
  30. Lander ES: Mapping complex genetic traits in humans. In: Davies KE (Ed.), Genome Analysis: A Practice Approach. Washington, D.C.: IRL Press, 1988; 171–189.Google Scholar
  31. Martinez MM, Goldin LR: Power of the linkage test for a heterogeneous disorder due to two independent inherited causes. Genet Epidemiol 1990; 7: 219–230.PubMedCrossRefGoogle Scholar
  32. Mendlewicz J, Fleiss JL: Linkage studies with X-chromosome markers in bipolar (manic-depressive) and unipolar (depressive) illness. Biol Psychiat 1974; 9: 261–294.PubMedGoogle Scholar
  33. Mendlewicz J, Linkowski P, Guroff JJ, Van Praag HM: Color blindness linkage to manic-depressive illness. Arch Gen Psychiat 1979; 36: 1442–1447.PubMedCrossRefGoogle Scholar
  34. Mendlewicz J, Linkowski P, Wilmotte J: Linkage between glucose-6-phosphate dehydrogenase deficiency and manic-depressive psychosis. Brit J Psychiat 1980; 137: 337–342.PubMedCrossRefGoogle Scholar
  35. Mendlewicz J, Simon P, Sevy S, Charon F, Brocas H, Legros S, Vassart G: Polymorphic DNA marker on X-chromosome and manic-depression. Lancet 1987; 1: 1230–1232.PubMedCrossRefGoogle Scholar
  36. Morton NE: Sequential tests for the detection of linkage. Am J Human Genet 1955; 7: 277–318.Google Scholar
  37. Nathans J, Plantanida TP, Eddy RL, Shows TB, Hogness DS: Molecular genetics of inherited variation in color vision. Science 1986; 232: 203–210.PubMedCrossRefGoogle Scholar
  38. Neiswanger K, Slaugenhaupt SA, Sughes HB, Frank E, Frankel DR, McCarty MJ, Charkravarti A, Zubenko GS, Kupfer DJ, Kaplan BB: Evidence against close linkage of unipolar affective illness to human chromosome llp markers HRAS1 and INS and chromosome Xq marker DXS52. Biol Psychiat 1990; 28: 63–72.PubMedCrossRefGoogle Scholar
  39. Oberle I, Drayna D, Camerino G, White R, Mandel JL: The telomeric region of the human X-chromosome long arm: Presence of a highly polymorphic DNA marker and analysis of recombination frequency. Proc Nat Acad Sci USA 1985; 82: 2824–2828.PubMedCrossRefGoogle Scholar
  40. O’Malley KL, Rotwein P: Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11. Nucleic Acids Res 1988; 16: 4437–4446.PubMedGoogle Scholar
  41. Ott J: Analysis of Human Genetic Linkage. Baltimore: John Hopkins University Press, 1985.Google Scholar
  42. Ott J: Invited editorial: Cutting the Gordian knot in the linkage analysis of complex human traits. Am J Human Genet 1990; 46: 219–221.Google Scholar
  43. Patterson M, Kenwrick S, Thibodeau S, Faulk K, Mattel MG, Mattel JF, Davies KE: Mapping of DNA markers close to the fragile site on the human X-chromosome at Xq27.3. Nucleic Acids Res 1987; 15: 2639–2651.PubMedCrossRefGoogle Scholar
  44. Ploughman LM, Boehnke M: Estimating the power of a proposed linkage study for a complex genetic trait. Am J Human Genet 1989; 44: 453–451.Google Scholar
  45. Rice J: The estimation of diagnostic sensitivity using stability data: An application to major depressive disorder. J Psychiat Res 1987; 21: 337–345.PubMedCrossRefGoogle Scholar
  46. Riordan JR, Rommens JM, Kerem BS, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Playsic N, Chou JL, Drumm ML, Iannuzzi MC, Collins FS, Tsue LC: Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 1990; 245: 1066–1073.CrossRefGoogle Scholar
  47. Risch N, Baron M, Mendlewicz J: Assessing X-linked inheritance in bipolar-related major affective disorder. J Psychiat Res 1986; 20: 275–288.PubMedCrossRefGoogle Scholar
  48. Risch N, Baron M: X-linkage and genetic heterogeneity in bipolar related major affective illness: Re-analysis of linkage date. Ann Human Genet 1982; 46: 153–166.CrossRefGoogle Scholar
  49. Risch N: Genetic linkage and complex diseases with special reference to psychiatric disorders. Genet Epidemiol 1990; 7: 3–16.PubMedCrossRefGoogle Scholar
  50. Rosanoff AJ, Handy L, Plesset IR: The etiology of manic-depressive syndromes with special references to their occurrence in twins. Am J Psychiat 1935; 91: 725–740.Google Scholar
  51. Smith M, Wasmuth J, McPherson JD, Wagner C, Grandy D, Civelli O, Potkin S, Litt M: Cosegregation of an 11q22.3–9p22 translocation with affective disorder: Proximity of the dopamine D2 receptor gene relative to the translocation breakpoint. Am J Human Genet 1989; 45(suppl): abstract 864.Google Scholar
  52. St. George-Hyslop PH, Tanzi HE, Polinsky RJ, Haines JI, Nee T, Watkins PC, Myers RH, Feldman RG, Pollen D, Drachman D, Growden J, Bruni A, Foncin J-F, Salmon D, Frommett P, Amaducci L, Sorbi S, Piacentini S, Stewart GD, Hobbs WJ, Conneally PM, Gusella JF: The genetic defect causing familial Alzheimer’s disease maps on chromosome 21. Science 1987; 235: 885.CrossRefGoogle Scholar
  53. Suarez BK: The affected sib-pair IBD distribution for HLA linked disease susceptibility loci. Tissue Antigens 1978; 12: 87–93.PubMedCrossRefGoogle Scholar
  54. Van Broeckhoven C, Van Hul W, Backhovens H, Van Camp G, Wehnert A, Stinissen P, Raeymaekers P, De Winter G, Gheuens J, Martin JJ, Vandenberghs A: The familial Alzheimer disease gene is located close to the centromere of chromosome 21. Am J Human Genet 1988; 43: a205.Google Scholar
  55. Winokur G, Clayton PJ, Reich T: Manic-Depressive Illness, St. Louis: C.V. Mosby Co., 1969, 112–125.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Wade H. Berrettini
    • 1
  1. 1.Department of Psychiatry and Human BehaviorJefferson Medical CollegePhiladelphiaUSA

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