The Role of Molecular Genetics in Psychiatry: Unraveling the Etiology for Schizophrenia

  • Lynn E. Delisi
  • Michael Lovett
Part of the International Perspectives Series: Psychiatry, Psychology, and Neuroscience book series


This chapter reviews the evidence for a genetic basis to schizophrenia. It also discusses attempts that have been made to discover some biological correlate that might be used as a marker for the disease, from the peripheral biochemical measurements to the protein and chromosomal marker studies, and finally the more recent application of systematic molecular genetic techniques to the study of this problem. This latter approach, which is the first step in what is now called “reverse genetics,” promises to yield great insights into the genetics, etiology, pathogenesis, and diagnostic boundaries of this disease.


Human Leukocyte Antigen Tyrosine Hydroxylase Schizophrenic Patient Fragile Site Pseudoautosomal Region 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kraepelin E: Lehrbuich der Psychiatrie, Diefendorf AR (trans). New York, MacMillan Company, 1907.Google Scholar
  2. 2.
    Gottesman II, Shields J: Schizophrenia: The Epigenetic Puzzle. New York, Cambridge University Press, 1982.Google Scholar
  3. 3.
    Rosenthal D: Familial concordance by sex with respect to schizophrenia. Psychol Bull 1962;59:401–421.PubMedCrossRefGoogle Scholar
  4. 4.
    Tsuang MT, Winokur G, Crowe RR: Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizophrenia, mania, depression, and surgical conditions. Br J Psych 1980;137:497–504.CrossRefGoogle Scholar
  5. 5.
    Guze SB, Cloninger CR, Martin RL, et al: A follow-up and family study of schizophrenia. Arch Gen Psychiatry 1983;40:1273–1276.PubMedGoogle Scholar
  6. 6.
    Baron M, Gruen R, Rainer JD, et al: A family study of schizophrenia and normal control probands: implications for the spectrum concept of schizophrenia. Am J Psychiatry 1985;142:447–454.PubMedGoogle Scholar
  7. 7.
    Gershon ES, DeLisi LE, Maxwell ME, et al: A controlled family study of psychosis. Arch Gen Psychiatry 1988;45:328–337.PubMedGoogle Scholar
  8. 8.
    Kendler KS: Overview: a current perspective on twin studies of schizophrenia. Am J Psychiatry 1983;140:1413–1425.PubMedGoogle Scholar
  9. 9.
    Carter CL, Chung CS: Segregation analysis of schizophrenia under a mixed genetic model. Human Heredity 1980;30:350–356.PubMedCrossRefGoogle Scholar
  10. 10.
    Rao DC, Morton NE, Gottesman II, et al: Path analysis of quantitative data on pairs of relatives: application to schizophrenia. Human Heredity 1981;31:325–333.PubMedCrossRefGoogle Scholar
  11. 11.
    McGue M, Gottesman II, Rao DC: The transmission of schizophrenia under a multifactorial threshold model. Am J Human Genetics 1983;35:1161–1178.Google Scholar
  12. 12.
    McGue M, Gottesman II, Rao, DC: Resolving genetic models for the transmission of schizophrenia. Genetic Epidemiol 1985;2:99–110.CrossRefGoogle Scholar
  13. 13.
    Risch N, Baron M: Segregation analysis of schizophrenia and related disorders. Am J Human Genetics 1984;36:1039–1059.Google Scholar
  14. 14.
    Rosenthal D, Wender PH, Kety SS, et al: The adopted away offspring of schizophrenics. Am J Psychiatry 1971;128:397–411.Google Scholar
  15. 15.
    Kety SS, Rosenthal D, Wender PH, et al: Mental illness in the biologic and adoptive families of adopted individuals who become schizophrenic: a preliminary report based on psychiatric interviews, in Fieve RR, Rosenthal D, Brill H (eds): Genetic Research in Psychiatry. Johns Hopkins University Press, Baltimore, 1975, pp 147–165.Google Scholar
  16. 16.
    Tienari P, Sorri A, Lahti I, et al: The Finnish adoptive family study of schizophrenia. Yale J Biol Med 1985;58:227–237.PubMedGoogle Scholar
  17. 17.
    Crow TJ, Done DJ: Age of onset of schizophrenia in siblings: a test of the contagion hypothesis. Psych Res 1986;18:107–117.CrossRefGoogle Scholar
  18. 18.
    Crow TJ: The continuum of psychosis and its implication for the structure of the gene. Br J Psychiatry 1986;149:419–428.PubMedCrossRefGoogle Scholar
  19. 19.
    Goldin IR, Kidd KK, Matthysse S, et al: The power of pedigree segregation analysis for traits with incomplete penetrance, in Gershon ES, Matthysse S, Ciaranello RD, Breakefield XO (eds): Genetic Strategies in Psychobiology and Psychiatry. Pacific Grove, CA, Boxwood Press, 1981, pp 305–317.Google Scholar
  20. 20.
    Goldwin IR, Cox NJ, Pauls DL, et al: The detection of major loci by segregation and linkage analysis: a stimulation study. Genetic Epidemiol 1984; 1:285–296.CrossRefGoogle Scholar
  21. 21.
    DeLisi LE, Goldin LR, Gershon ES: Studies of biological factors associated with the inheritance of schizophrenia: a selective review. J Psychiatric Res 1987;21:507–513.CrossRefGoogle Scholar
  22. 22.
    Erlenmeyer-Kimling L: Biological markers for the liability to schizophrenia, in Helmchen H, Henn FA (eds): Biological Perspectives in Schizophrenia: Dahlem Workshop Reports LS 40. Cambridge, Wiley and Sons, 1987, pp 33–56.Google Scholar
  23. 23.
    DeLisi LE, Wise CD, Bridge TP, et al: Monoamine oxidase and schizophrenia, in Usdin E, Hamin I (eds): Biological Markers in Psychiatry and Neurology. Oxford, Pergamon Press, 1982, pp 89–96.Google Scholar
  24. 24.
    Nies A, Robinson DS, Lamborn KR, et al: Genetic control of platelet and plasma monoamine oxidase activity. Arch Gen Psychol. 1971;28:834–838.Google Scholar
  25. 25.
    Wyatt RJ, Murphy DL, Belmaker R, et al: Reduced monoamine oxidase in platelets: a possible marker for vulnerability to schizophrenia. Science 1973;179:916–918.PubMedCrossRefGoogle Scholar
  26. 26.
    Reveley MA, Reveley AM, Clifford CA, et al: Genetics of platelet MAO activity in discordant schizophrenic and normal twins. Br J Psychiatry 1983;142:89–93.CrossRefGoogle Scholar
  27. 27.
    DeLisi LE, Wise CD, Bridge TP, et al: A probable neuroleptic effect on platelet monoamine oxidase activity. Psychiatry Res 1981;4:95–107.CrossRefGoogle Scholar
  28. 28.
    Owen F, Bourne RC, Crow TJ, et al: Platelet monoamine oxidase activity in acute schizophrenia: relationship to symptomatology and neuroleptic medication. Br J Psychiatry 1981;139:16–22.PubMedCrossRefGoogle Scholar
  29. 29.
    Weinshilbaum RM, Schrott HG, Raymond FA, et al: Inheritance of very low serum dopamine-beta-hydroxlase activity. Am J Human Genetics 1975; 27:573–585.Google Scholar
  30. 30.
    Weinshilbaum RM, Raymond FA: Inheritance of low erythrocyte catechol- O-methyltransferase activity in man. Am J Human Genetics 1977;29:125–135.Google Scholar
  31. 31.
    Sedvall GC, Wode-Helgodt B: Aberrant monoamine metabolite levels in CSF and family history of schizophrenia. Arch Gen Psychiatry 1980;37:1113–1116.PubMedGoogle Scholar
  32. 32.
    Sedvall GC, Fyro B, Gullberg B, et al: Relationships in healthy volunteers between concentrations of monoamine metabolites in cerebrospinal fluid and family history of psychiatric morbidity. Br J Psychiatry 1980;136:366–374.PubMedCrossRefGoogle Scholar
  33. 33.
    Oxenstierna G, Edman G, Iselius L, et al: Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals—a genetic study. J Psychiatr Res 1986;20:19–29.PubMedCrossRefGoogle Scholar
  34. 34.
    Kornhuber J, Riederer P, Reynolds GP, et al: 3H-spiperone binding sites in postmortem brains from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms. J Neural Transmission 1989;75:1–10.CrossRefGoogle Scholar
  35. 35.
    Wong DF, Wagner HN, Tune LE, et al: Positron emission tomography reveals elevated brain D-2 dopamine receptors in schizophrenia. Science 1986;234:1558–1563.PubMedCrossRefGoogle Scholar
  36. 36.
    Farde L, Wiesel F-A, Hall H, et al: No D2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 1987;44:671–672.PubMedGoogle Scholar
  37. 37.
    Bondy B, Ackenheil M: 3H-spiperone binding sites in lymphocytes as possible vulnerability marker in schizophrenia. J Psychiatr Res 1987;21:521–529.PubMedCrossRefGoogle Scholar
  38. 38.
    Reveley AM, Reveley MA, Clifford CA, et al: Cerebral ventricular size in twins discordant for schizophrenia. Lancet 1982; i:540–541.CrossRefGoogle Scholar
  39. 39.
    DeLisi LE, Goldin LR, Hamovit JR, et al: A family study of the association of increased ventricular size with schizophrenia. Arch Gen Psychiatry 1986;43:148–153.Google Scholar
  40. 40.
    Reveley AM, Reveley MA, Murray RM: Cerebral ventricular enlargement in nongenetic schizophrenia: a controlled twin study. Br J Psych 1984;144:89–93.CrossRefGoogle Scholar
  41. 41.
    Lipton RB, Levy DL, Holzman PS, et al: Eye movement dysfunctions in psychiatric patients: a review. Schizophrenia Bulletin 1983;9:13–22.PubMedGoogle Scholar
  42. 42.
    Holzman PS: Eye movement dysfunction and psychosis. Int Rev Neurobiol 1985;27:179–205.PubMedCrossRefGoogle Scholar
  43. 43.
    Holzman PS, Proctor LR, Levy DL, et al: Eye-tracking dysfunctions in schizophrenic patients and their relatives. Arch Gen Psychiatry 1974;31:143–151.PubMedGoogle Scholar
  44. 44.
    Holzman PS, Kringlen E, Levy DL, et al: Deviant eye tracking in twins discordant for psychosis: a replication. Arch Gen Psychiatry 1980,32:627–631.Google Scholar
  45. 45.
    Matthysse S, Holzman PS, Lange K: The genetic transmission of schizophrenia: application of Mendelian latent structure analysis to eye-tracking dysfunction in schizophrenia and affective disorder. J Psychiatric Res 1986;20:57–67.CrossRefGoogle Scholar
  46. 46.
    Turner WD: Genetic markers for schizotaxia. Biol Psychol. 1979;14:177–205.Google Scholar
  47. 47.
    McGuffin P, Festenstein H, Murray R: A family study of HLA antigens and other genetic markers in schizophrenia. Psychological Medicine 1983;13:31–43.PubMedCrossRefGoogle Scholar
  48. 48.
    Goldin LR, DeLisi LE, Gershon ES: The relation of HLA to schizophrenia in 10 nuclear families. Psychiatry Res 1987;20:69–77.PubMedCrossRefGoogle Scholar
  49. 49.
    McGuffin P, Sturt E: Genetic markers in schizophrenia. Human Heredity 1986;36:65–88.Google Scholar
  50. 50.
    Goldin LR, Gershon ES: Association and linkage studies of genetic marker loci in major psychiatric disorders. Psychiatric Devel 1983;4:387–418.Google Scholar
  51. 51.
    Book JA, Wetterberg L, Modrzewska K: Schizophrenia in a north Swedish geographical isolate, 1900–1917. Epidemiology, genetics, and biochemistry. Clin Genetics 1978;14:373–394.CrossRefGoogle Scholar
  52. 52.
    Ruddick C, Granzen G, Hanson A, et al: G serum groups in schizophrenia. Human Heredity 1985;35:11–14.CrossRefGoogle Scholar
  53. 53.
    Ruddick C, Beckman L, Franzen G, et al: C3 and C6 complement types in schizophrenia. Human Heredity 1985;35:255–258.CrossRefGoogle Scholar
  54. 54.
    Cowie V, Coppen A, Norman P: Nuclear sex and body build in schizophrenia. Br Med J 1960;ii:431–433.CrossRefGoogle Scholar
  55. 55.
    Tedeschi L, Freeman D: Sex chromosomes in male schizophrenics. Arch Gen Psychiatry 1962;6:17–19.Google Scholar
  56. 56.
    Raphael T, Shaw MW: Chromosome studies in schizophrenia. JAMA 1963;183:1022–1028.PubMedGoogle Scholar
  57. 57.
    Nielsen J, Fisher M: Sex chromatin and sex chromosome abnormalities in male hypogonadal mental patients. Br J Psychiatry 1965;111:641–647.PubMedCrossRefGoogle Scholar
  58. 58.
    Asaka A, Tsuboit T, Inove E, et al: Schizophrenic psychosis in triple-X females. Folia Psychiatr Neurol Jap 1967;21:271–81.Google Scholar
  59. 59.
    Judd LL, Brandkamp WW: Chromosome analyses of adult schizophrenics. Arch Gen Psychiatry 1967;16:316–324.PubMedGoogle Scholar
  60. 60.
    Anders JM, Jagiello G, Polani PE, et al: Chromosome findings in chronic psychotic patients. Br J Psychiatry 1968;114:1167–1174.PubMedCrossRefGoogle Scholar
  61. 61.
    MacLean, N, Court-Brown WM, Jacobs PA, et al: A survey of sex chromatin abnormalities in mental hospitals. J. Medical Genetics 1968;5:165–172.CrossRefGoogle Scholar
  62. 62.
    Kaplan AR: Chromosomal mosaicisms and occasional acentric chromosomal fragments in schizophrenic patients. Biological Psychiatry 1970;2:89–94.PubMedGoogle Scholar
  63. 63.
    Vartanian ME, Gendelis VM: The role of chromosomal aberrations in the clinical polymorphism of schizophrenia. Int J Ment Health 1972;1:93–106.Google Scholar
  64. 64.
    Dasgupta J, Dasgupta D, Balasubrahmanyan M: XXY syndrome XY/XO mosaicism and acentric chromosomal fragments in male schizophrenics. Indian J Med Res 1973;61:62–70.PubMedGoogle Scholar
  65. 65.
    Trixler M, Kosztolani G, Mehes K: Sex chromosome aberration screening among male psychiatric patients. Arch Psychiat Nervenkr 1976;221:273–282.PubMedCrossRefGoogle Scholar
  66. 66.
    Axelsson R, Wahlstrom J: Chromosome aberrations in patients with paranoid psychosis. Hereditas 1984;100:19–31.Google Scholar
  67. 67.
    DeLisi LE, Reiss AL, White BJ, et al: Cytogenetic studies of males with schizophrenia: screening for the fragile X chromosome and other chromosomal abnormalities. Schizophrenia Res 1988;1:277–281.CrossRefGoogle Scholar
  68. 68.
    Hamerton JL, Canning N, Ray M, et al: A cytogentic survey of 14,069 newborn infants I. Incidence of chromosomal abnormalities. Clin Genetics 1975;8:223–243.CrossRefGoogle Scholar
  69. 69.
    Ratcliffe SG, Murray L, Teague P: Edinburgh study of growth and development of children with sex chromosome abnormalities III. Birth Defects 1986;22:73–118.PubMedGoogle Scholar
  70. 70.
    Money J, Hirsch SR: Chromosome anomalies, mental deficiency, and schizophrenia. Arch Gen Psychol 1963;8:54–63.Google Scholar
  71. 71.
    Polani PE: Abnormal sex chromosomes and mental disorder. Nature 1969;223:680–686.PubMedCrossRefGoogle Scholar
  72. 72.
    Forssman H: The mental implications of sex chromosome aberrations. Br J Psychiatry 1970;117:353–63.PubMedCrossRefGoogle Scholar
  73. 73.
    Turner G, Gill R, Daniel A: Marker X chromosomes, mental retardation, and macroorchidism. N Engl J Med 1978;299:1472.PubMedGoogle Scholar
  74. 74.
    Rogers RC, Simensen RJ: Fragile X syndrome: a common etiology of mental retardation. Am J Mental Defic 1987;91(5):445–449.Google Scholar
  75. 75.
    Webb TP, Thake Al, Bundey SE, et al: A cytogenetic survey of a mentally retarded school age population with special reference to fragile sites. J Mental Defic Res 1987; 31 (part 1):61–71.Google Scholar
  76. 76.
    Martin JB, Bell J: A pedigree of mental defect showing sex linkage. J Neurol Psychiatry 1943;6:154–157.PubMedCrossRefGoogle Scholar
  77. 77.
    Brown WT, Jenkins EC, Cohen IL, et al: Fragile X and autism: a multicenter survey. Am J Med Genetics 1986;23:341–52.CrossRefGoogle Scholar
  78. 78.
    Reiss AL, Feinstein C, Toomey KE, et al: Psychiatric disability associated with the fragile X chromosome. Am J Med Genetics 1986;23:393–402.CrossRefGoogle Scholar
  79. 79.
    Reiss AL, Hagerman RJ, Vinogradov S, et al: Psychiatric disability in female carriers of the fragile X chromosome. Arch Gen Psychiatry 1988;45:25–30.PubMedGoogle Scholar
  80. 80.
    Crow TJ: Pseudoautosomal locus for psychoses? Lancet 1987;ii: 1532.CrossRefGoogle Scholar
  81. 81.
    Crow TJ: Sex chromosomes and psychosis: the case for a pseudoautosomal locus. Br J Psychiatry 1988;153:675–683.PubMedCrossRefGoogle Scholar
  82. 82.
    Crow TJ, DeLisi LE, Johnstone EC: Clues to the nature and location of the psychosis gene: is schizophrenia due to an anomaly of the cerebral dominance gene located in the pseudoautosomal region of the sex chromosomes? in Wetterberg L (ed): Genetics of Neuropsychiatric Diseases. Wenner-Gren Center International Symposium No. 51. New York, McMillan Press, 1989.Google Scholar
  83. 83.
    Rouyer F, Simmler M-C, Johnsson C, et al: A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes. Nature 1986;319:291–295.PubMedCrossRefGoogle Scholar
  84. 84.
    Rouyer, F, Simmler M-C, Vergnaud G, et al: The pseudoautosomal region of the human sex chromosomes. Cold Spring Harbor Symposia on Quantitative Biology 1986;LI:221–228.Google Scholar
  85. 85.
    Page DC, Bieker K, Brown LG, et al: Linkage, physical mapping, and DNA sequence analysis of pseudoautosomal loci on the human X and Y chromosomes. Genomics 1987;1:243–256.PubMedCrossRefGoogle Scholar
  86. 86.
    DeLisi LE, Goldin LR, Maxwell ME, et al: Clinical features of illness in siblings with schizophrenia or schizoaffective disorder. Arch General Psychiatry 1987;44:891–896.Google Scholar
  87. 87.
    Schulz B: Zur Erbpathologie der schizophrenic. Zeitschrift Gesammie Neu- rologie und Psychiatrie 1932;143:175–293.CrossRefGoogle Scholar
  88. 88.
    Zehnder M: Uber Krankheitsbild und Krankheitsverlauf bei schizophrenen Geschwistern. Monatschrift fur Psychiatrie und Neurologie 1941; 103:231–277.CrossRefGoogle Scholar
  89. 89.
    Penrose LS: Survey of cases of familiar mental illness. Digest Neurology Psychiatry 1945;13:644.Google Scholar
  90. 90.
    Tsuang MT: A study of pairs of sibs both hospitalized for mental disorder. Br J Psychiatry 1967;113:283–300.PubMedCrossRefGoogle Scholar
  91. 91.
    Rudduck C, Franzen G: Brief report: a new heritable fragile site on human chromosome 3. Hereditas 1983;98:297–299.PubMedCrossRefGoogle Scholar
  92. 92.
    Chodirker BN, Chudley AE, Ray M, et al: Fragile 19pl3 in a family with mental illness. Clinical Genetics 1987;31:1–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Sperber MA: Schizophrenia and organic brain syndrome with trisomy 8 (group C trisomy 8 [47, XX,8 + ]). Biol Psychiatry 1975;10:27–43.PubMedGoogle Scholar
  94. 94.
    Bassett AS, McGillivray BC, Jones BD, et al: Partial trisomy chromosome 5 cosegregating with schizophrenia. Lancet 1988;i:799–801.CrossRefGoogle Scholar
  95. 95.
    Genest, P, Dumas L, Genest FB: Translocation chromosomique t (2; 18) (q21;q23) chez un individual schizophrene et sa fille. L’Union Me die ale Du Canada TOME 1976;105:1617–1681.Google Scholar
  96. 96.
    White RL: DNA in medicine: human genetics. Lancet 1984;ii: 1257–1262.CrossRefGoogle Scholar
  97. 97.
    Gershon ES, Merrill CR, Goldin LR, et al: The role of molecular genetics in psychiatry. Biol Psychiatry 1987;22:1388–1405.PubMedCrossRefGoogle Scholar
  98. 98.
    Baron M, Rainer JD: Molecular genetics and human disease: implications for modern psychiatric research and practice. Br J Psychol 1988;152:741–753.CrossRefGoogle Scholar
  99. 99.
    Maniatis T, Fritsch EF, Sambrook J: Molecular Cloning: A Laboratory Manual. New York, Cold Spring Harbor Laboratory, 1982.Google Scholar
  100. 100.
    Gusella JF, Wexler NS, Conneally PM, et al: A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 1983;306:234–238.PubMedCrossRefGoogle Scholar
  101. 101.
    Egeland JR, Gerrhard DS, Pauls DL, et al: Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 1987;325:783–787.PubMedCrossRefGoogle Scholar
  102. 102.
    Mendlewicz J, Sevy S, Brocas H, et al: Polymorphic DNA marker on X chromosome and manic depression. Lancet 1987;i: 1230–1232.CrossRefGoogle Scholar
  103. 103.
    Tanzi RE, Gusella FF, Watkins PC, et al: Amyloid beta-protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 1987;235:880–884.PubMedCrossRefGoogle Scholar
  104. 104.
    Feder J, Gurling HMD, Darby J, et al: DNA restriction fragment analysis of the proopiomelanocortin gene in schizophrenia and bipolar disorders. Am J Human Genetics 1985;37:286–294.Google Scholar
  105. 105.
    Detera-Wadleigh, S, DeLisi LE, Berrettini WH, et al: DNA polymorphisms in schizophrenia and affective disorders, in Shagass C, et al. (eds): Proceedings of the IVth World Congress of Biological Psychiatry. New York, Elsevier Publishing Co., 1986.Google Scholar
  106. 106.
    Detera-Wadleigh SD, deMiguel C, Berrettini WH, et al: Neuropeptide gene polymorphisms in affective disorder and schizophrenia. J Psychiatric Res 1987; 21 (4): 581–587.CrossRefGoogle Scholar
  107. 107.
    Sherrington R, Brynjolfsson J, Petersson, H, et al: Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 1988;336:164–167.PubMedCrossRefGoogle Scholar
  108. 108.
    Kennedy JL, Gluffrat LA, Moises HW, et al: Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. Nature 1988;336:167–170.PubMedCrossRefGoogle Scholar
  109. 109.
    Gershon ES: Presented at the 27th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, Dec 12–16, 1988.Google Scholar
  110. 110.
    Crow TJ: Two syndromes of schizophrenia as one pole of the continuum of psychosis: a concept of the nature of the pathogen and its genetic locus, in Henn FA, DeLisi LE (eds): Neurochemistry and Neuropharmacology of Schizophrenia. Amsterdam, Elsevier, 1987, pp 17–48.Google Scholar
  111. 111.
    DeLisi LE, Wyatt RJ: Endogenous hallucinogens and other behavior modifying factors in schizophrenia, in Henn FA, DeLisi LE (eds): Neurochemistry and Neuropharmacology of Schizophrenia. Amsterdam, Elsevier, 1987, pp 377–390.Google Scholar
  112. 112.
    Stahl SM, Wets K: Indoleamines and schizophrenia, in Henn FA, DeLisi LE (eds): Neurochemistry and Neuropharmacology of Schizophrenia. Amsterdam, Elsevier, 1987, pp 257–296.Google Scholar
  113. 113.
    DeLisi LE, Wyatt RJ: Neurochemical aspects of schizophrenia, in Lajtha JR (ed): Handbook of Neurochemistry, New York, Plenum Publishing Co, 1985, vol 10, pp 553–587.Google Scholar
  114. 114.
    Bach AWJ, Lan NC, Johnson DL, et al: cDNA cloning of human liver mo- noamie oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 1988;85:4934–4938.PubMedCrossRefGoogle Scholar
  115. 115.
    Ozelius L, Hsu Y-PP, Bruns G, et al: Human monoamine oxidase gene (MAOA): chromosome position (Xp21-pll) and DNA polymorphism, in Genomics 198 Biochemical Basis of Neuropharmacology, ed 4. New York, Oxford University Press, 1982, pp 295–320.Google Scholar
  116. 116.
    Woo SLC, Lidsky AS, Guttler F, et al: Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature 1983;306,151–155.PubMedCrossRefGoogle Scholar
  117. 117.
    Woo SLC, DiLella AG, Marvit J, et al: Molecular basis of phenylketonuria and potential somatic gene therapy. Cold Spring Harbor Symposia on Quantitative Biology 1986;LI,395–401.Google Scholar
  118. 118.
    Cooper JR, Bloom FE, Roth RH: Neuroactive peptides, chap 10, in The Biochemical Basis of Neuropharmacology, ed 4. New York, Oxford University Press, 1982, pp 295–320.Google Scholar
  119. 119.
    Roberts GW, Ferrier IN, Lee Y, et al: Peptides, the limbic lobe and schizophrenia. Brain Research 1983;288:199–211.PubMedCrossRefGoogle Scholar
  120. 120.
    Crow TJ, Deakin JFW: Neurotransmitters, behavior, and metal disorder, in Shephard M (ed): Handbook of Psychiatry. Cambridge, Cambridge University Press, 1985, vol. 5, pp 137–182.Google Scholar
  121. 121.
    Crow TJ: A reevaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene. Br J Psychiatry 1984;145:243–253.PubMedCrossRefGoogle Scholar
  122. 122.
    Jeffreys AJ, Wilson V, Thein SL: Hypervariable “minisatellite” regions in human DNA. Nature 1985;314:67–73.PubMedCrossRefGoogle Scholar
  123. 123.
    Nakamura Y, Leppert M, O’Connell P, et al: Variable number of tandem repeat (VNIR) markers for human gene mapping. Science 1987;235:1616–1622.PubMedCrossRefGoogle Scholar
  124. 124.
    Church G, Kieffer-Higginss: Multiple DNA sequencing. Science 1988,240: 185–188.Google Scholar
  125. 125.
    Bird AP: CpG-rich islands and the function of DNA methylation. Nature 1986;321:209–213.PubMedCrossRefGoogle Scholar
  126. 126.
    Smith CL, Econome JG, Schutt A, et al: A physical map of the Escherichia coli K12 genome. Science 1987;236:1448–1453.PubMedCrossRefGoogle Scholar
  127. 127.
    Lawrence SK, Smith CL, Srivastava R, et al: Megabase scale mapping of the HLA gene complex by pulsed field gel electrophoresis. Science 1987;235:1387–1390.CrossRefGoogle Scholar
  128. 128.
    Smith CL, Cantor CR: Approaches to physical mapping of the human genome. Cold Spring Harbor Symp Quart Biol 1986;51:115–122.Google Scholar
  129. 129.
    Smith CL, Cantor CR: Preparation and manipulation of large DNA molecules: advances and applications. TIBS 1987; 12(8):284–287.Google Scholar
  130. 130.
    Church GM, Gilbert W: Genomic sequencing: preliminary communication. Proc. Natl Acad Sci USA 1984;81:1991–1995.PubMedCrossRefGoogle Scholar
  131. 131.
    Scharf SJ, Horn GT, Erlich HA: Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science 1986;233:1076–1078.PubMedCrossRefGoogle Scholar
  132. 132.
    Engelke DR, Hoener PA, Collins FS: Direct sequencing of enzymatically amplified human genomic DNA. Proc Natl Acad Sci USA 1988;85:544–548.PubMedCrossRefGoogle Scholar
  133. 133.
    Morton NE: The detection and estimation of linkage between the genes for elliptocytosis and RH blood type. Am J Human Genetics 1956;8:80–96.Google Scholar
  134. 134.
    Ott J: Analysis of Human Genetic Linkage. Baltimore and London, Johns Hopkins University Press, 1985.Google Scholar
  135. 135.
    Ott J: Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage. Am J Human Genetics 1974;26:588–597.Google Scholar
  136. 136.
    Lathrop GM, Lalouel JM, Julier C, et al: Strategies for multilocus linkage analysis in humans. PNAS 1984;81:3443–3446.PubMedCrossRefGoogle Scholar
  137. 137.
    Gershon ES, Goldin IR: The outlook for linkage research in psychiatric disorders. J Psychiatric Res 1987;21:541–550.CrossRefGoogle Scholar
  138. 138.
    Penrose LS: The detection of autosomal linkage in data which consists of pairs of brothers and sisters of unspecificied parentage. Ann Eugenics 1935;6:133–138.CrossRefGoogle Scholar
  139. 139.
    Penrose LS: The general purpose sib-pair linkage test. Ann Eugenics 1953;18:120–124.CrossRefGoogle Scholar
  140. 140.
    Thomson G, Bodmer WF: The genetic analysis of HLA and disease associations, in Dausset J, Svejgaard A (eds): HLA and Disease. Baltimore, Williams and Wilkins, 1987, pp 84–93.Google Scholar
  141. 141.
    Suarez BIK: The affected sib-pair IBD distribution for HLA linked disease susceptibility loci. Tissue Antigens 1978;12:87–93.PubMedCrossRefGoogle Scholar
  142. 142.
    Green JR, Woodrow JC: Sibling method for detecting HLA-linked genes in disease. Tissue Antigens 1977;9:31–35.PubMedCrossRefGoogle Scholar
  143. 143.
    Clerget-Darpoux F, Govaerts A, Feingold N: HLA and susceptibility to multiple sclerosis. Tissue Antigens 1984;24:160–169.PubMedCrossRefGoogle Scholar
  144. 144.
    Collins FS, Weissman SM: Directional cloning of DNA fragments at a large distance from an initial probe: a circulization method. Proc Natl Acad Sci USA 1984;81:6812–6816.PubMedCrossRefGoogle Scholar
  145. 145.
    Poustka A, Lehrach H: Jumping libraries and linking libraries. The next generation of molecular tools in mammalian genetics. Trends Genet 1986;2:174–179.Google Scholar
  146. 146.
    Burke DT, Carle GF, Olson MV: Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 1987;236:806–812.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • Lynn E. Delisi
  • Michael Lovett

There are no affiliations available

Personalised recommendations