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Abstract

There has been substantial evidence for more than three decades that the major psychiatric illnesses such as schizophrenia, bipolar disorder, autism, and alcoholism have a strong genetic basis. During the past 15 years considerable effort has been expended in trying to establish the genetic loci associated with susceptibility to these and other mental disorders using principally linkage analysis. Despite this, only a handful of specific genes have been identified, and it is now generally recognized that further advances along these lines will require the analysis of literally hundreds of affected individuals and their families. Fortunately, the emergence in the past three years of a number of new approaches and more effective tools has given new hope to those engaged in the search for the underlying genetic and environmental factors involved in causing these illnesses, which collectively are among the most serious in all societies. Chief among these new tools is the availability of the entire human genome sequence and the prospect that within the next several years the entire complement of human genes will be known and the functions of most of their protein products elucidated. In the meantime the search for susceptibility loci is being facilitated by the availability of single nucleotide polymorphisms (SNPs) and by the beginning of haplotype mapping, which tracks the distribution of clusters of SNPs that segregate as a group. Together with high throughput DNA sequencing, microarrays for whole genome scanning, advances in proteomics, and the development of more sophisticated computer programs for analyzing sequence and association data, these advances hold promise of greatly accelerating the search for the genetic basis of most mental illnesses while, at the same time, providing molecular targets for the development of new and more effective therapies.

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2002-03-01
2024-06-18
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Literature Cited

  1. Aita VM, Liu J, Knowles JA, Terwilliger JD, Baltazar R. et al. 1999. A comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective disorder locus.. Am. J. Hum. Genet. 64:210–17 [Google Scholar]
  2. Amir RE, Zoghbi HY. 2000. Rett syndrome: methyl-CpG-binding protein 2 mutations and phenotype-genotype correlations.. Am. J. Med. Genet. 97:147–52 [Google Scholar]
  3. Antonarakis SE, Blouin JL, Curran M. 1996. Linkage and sib-pair analysis reveal a potential schizophrenia susceptibility gene on chromosome 13q32.. Am. J. Hum. Genet. 59:A210 [Google Scholar]
  4. Antonarakis SE, Blouin JL, Pulver AE, Wolyniec P, Lasseter VK. et al. 1995. Schizophrenia susceptibility and chromosome 6p24-22.. Nat. Genet. 11:235–36 [Google Scholar]
  5. Ashley-Koch A, Wolpert CM, Menold MM, Zaeem L, Basu S. et al. 1999. Genetic studies of autistic disorder and chromosome 7.. Genomics 61:227–36 [Google Scholar]
  6. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E. et al. 1995. Autism as a strongly genetic disorder: evidence from a British twin study.. Psychol. Med. 25:63–77 [Google Scholar]
  7. Barden N, Morissette J. 1999. Chromosome 13 workshop report.. Am. J. Med. Genet. 88:260–62 [Google Scholar]
  8. Baron M. 1977. Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness.. Occurrence in the family of a lithium carbonate-responsive schizo-affective pro band Arch. Gen. Psychiatry 34:721–25 [Google Scholar]
  9. Baron M. 2001. Genetics of schizophrenia and the new millennium: progress and pitfalls.. Am. J. Hum. Genet. 68:299–312 [Google Scholar]
  10. Baron M, Freimer NF, Risch N, Lerer B, Alexander JR. et al. 1993. Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.. Nat. Genet. 3:49–55 [Google Scholar]
  11. Baron M, Risch N, Hamburger R, Mandel B, Kushner S. et al. 1987. Genetic linkage between X-chromosome markers and bipolar affective illness.. Nature 326:289–92 [Google Scholar]
  12. Bass MP, Menold MM, Wolpert CM, Donnelly SL, Ravan SA. et al. 1999. Genetic studies in autistic disorder and chromosome 15.. Neurogenetics 2:219–26 [Google Scholar]
  13. Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S. et al. 1994. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.. Proc. Natl. Acad. Sci. USA 91:5918–21 [Google Scholar]
  14. Berrettini WH, Goldin LR, Gelernter J, Gejman PV, Gershon ES, Detera-Wadleigh S. 1990. X-chromosome markers and manic-depressive illness.. Rejection of linkage to Xq28 in nine bipolar pedigrees Arch. Gen. Psychiatry 47:366–73 [Google Scholar]
  15. Bird TD, Wijsman EM, Nochlin D, Leehey M, Sumi SM. et al. 1997. Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD.. Neurology 48:949–54 [Google Scholar]
  16. Blackwood DH, He L, Morris SW, McLean A, Whitton C. et al. 1996. A locus for bipolar affective disorder on chromosome 4p.. Nat. Genet. 12:427–30 [Google Scholar]
  17. Blazer DG, Kessler RC, McGonagle KA, Swartz MS. 1994. The prevalence and distribution of major depression in a national community sample: The National Comorbidity Survey.. Am. J. Psychiatry 151:979–86 [Google Scholar]
  18. Blouin JL, Dombroski BA, Nath SK, Lasseter VK, Wolyniec PS. et al. 1998. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.. Nat. Genet. 20:70–73 [Google Scholar]
  19. Bolton P, Macdonald H, Pickles A, Rios P, Goode S. et al. 1994. A case-control family history study of autism.. J. Child Psychol. Psychiatry 35:877–900 [Google Scholar]
  20. Brzustowicz LM, Hodgkinson KA, Chow EW, Honer WG, Bassett AS. 2000. Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22.. Science 288:678–82 [Google Scholar]
  21. Brzustowicz LM, Honer WG, Chow EW, Little D, Hogan J. et al. 1999. Linkage of familial schizophrenia to chromosome 13q32.. Am. J. Hum. Genet. 65:1096–103 [Google Scholar]
  22. Busatto GF, Costa DC, Ell PJ, Pilowsky LS, David AS, Kerwin RW. 1994. Regional cerebral blood flow (rCBF) in schizophrenia during verbal memory activation: a 99mTc-HMPAO single photon emission tomography (SPET) study.. Psychol. Med. 24:463–72 [Google Scholar]
  23. Callicott JH, Mattay VS, Bertolino A, Finn K, Coppola R. et al. 1999. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI.. Cereb. Cortex 9:20–26 [Google Scholar]
  24. Cannon TD, Kaprio J, Lonnqvist J, Huttunen M, Koskenvuo M. 1998. The genetic epidemiology of schizophrenia in a Finnish twin cohort.. A population-based modeling study Arch. Gen. Psychiatry 55:67–74 [Google Scholar]
  25. Cao Q, Martinez M, Zhang J, Sanders AR, Badner JA. et al. 1997. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees.. Genomics 43:1–8 [Google Scholar]
  26. Cardno AG, Gottesman II. 2000. Twin studies of schizophrenia: from bow-and-arrow concordances to Star Wars Mx and functional genomics.. Am. J. Med. Genet. 97:12–17 [Google Scholar]
  27. Cardno AG, Holmans PA, Rees MI, Jones LA, McCarthy GM. et al. 2001. A genome-wide linkage study of age at onset in schizophrenia.. Am. J. Med. Genet. 105:439–45 [Google Scholar]
  28. Choi DW. 2000. Hearing before the Appropriations Subcommittee of the House Committee on Labor, Health and Human Services, 106th Cong, 2nd sess.. http://www.sfn.org/news
  29. Barrett S, Beck JC, Bernier R, Bisson E. Collaborative Linkage Study of Autism, et al. 1999. An autosomal genomic screen for autism.. Am. J. Med. Genet. 88:609–15 [Google Scholar]
  30. Collins FS, McKusick VA. 2001. Implications of the Human Genome Project for medical science.. JAMA 285:540–44 [Google Scholar]
  31. Cook-Deegan R. 1994. The Gene Wars. New York: Norton [Google Scholar]
  32. Cook EH Jr, Courchesne RY, Cox NJ, Lord C, Gonen D. et al. 1998. Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.. Am. J. Hum. Genet. 62:1077–83 [Google Scholar]
  33. Coon H, Holik J, Hoff M, Reimherr F, Wender P. et al. 1994a. Analysis of chromosome 22 markers in nine schizophrenia pedigrees.. Am. J. Med. Genet. 54:72–79 [Google Scholar]
  34. Coon H, Jensen S, Holik J, Hoff M, Myles-Worsley M. et al. 1994b. Genomic scan for genes predisposing to schizophrenia.. Am. J. Med. Genet. 54:59–71 [Google Scholar]
  35. Cowan WM, Kandel ER. 2001. Prospects for neurology and psychiatry.. JAMA 285:594–600 [Google Scholar]
  36. Dann J, DeLisi LE, Devoto M, Laval S, Nancarrow DJ. et al. 1997. A linkage study of schizophrenia to markers within Xp11 near the MAOB gene.. Psychiatry Res. 70:131–43 [Google Scholar]
  37. Davies K. 2001. Cracking the Genome. New York: Free Press [Google Scholar]
  38. Del Zompo M, Bocchetta A, Goldin LR, Corsini GU. 1984. Linkage between X-chromosome markers and manic-depressive illness.. Two Sardinian pedigrees Acta Psychiatr. Scand. 70:282–87 [Google Scholar]
  39. DeLisi LE, Devoto M, Lofthouse R, Poulter M, Smith A. et al. 1994a. Search for linkage to schizophrenia on the X and Y chromosomes.. Am. J. Med. Genet. 54:113–21 [Google Scholar]
  40. DeLisi LE, Friedrich U, Wahlstrom J, Boccio-Smith A, Forsman A. et al. 1994b. Schizophrenia and sex chromosome anomalies.. Schizophr. Bull. 20:495–505 [Google Scholar]
  41. Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin LR. et al. 1999. A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2.. Proc. Natl. Acad. Sci. USA 96:5604–9 [Google Scholar]
  42. Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR. et al. 1996. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q.. Am. J. Hum. Genet. 58:1279–85 [Google Scholar]
  43. Detera-Wadleigh SD, Badner JA, Yoshikawa T, Sanders AR, Goldin LR. et al. 1997. Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q.. Am. J. Med. Genet. 74:254–62 [Google Scholar]
  44. Detera-Wadleigh SD, Hsieh WT, Berrettini WH, Goldin LR, Rollins DY. et al. 1994. Genetic linkage mapping for a susceptibility locus to bipolar illness: chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter.. Am. J. Med. Genet. 54:206–18 [Google Scholar]
  45. Edenberg HJ, Foroud T, Conneally PM, Sorbel JJ, Carr K. et al. 1997. Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.. Am. J. Med. Genet. 74:238–46 [Google Scholar]
  46. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM. et al. 2001. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.. Proc. Natl. Acad. Sci. USA 98:6917–22 [Google Scholar]
  47. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK. et al. 1987. Bipolar affective disorders linked to DNA markers on chromosome 11.. Nature 325:783–87 [Google Scholar]
  48. Evans KL, Muir WJ, Blackwood DH, Porteous DJ. 2001. Nuts and bolts of psychiatric genetics: building on the human genome project.. Trends Genet. 17:35–40 [Google Scholar]
  49. Ewald H, Degn B, Mors O, Kruse TA. 1998a. Significant linkage between bipolar affective disorder and chromosome 12q24.. Psychiatr. Genet. 8:131–40 [Google Scholar]
  50. Ewald H, Degn B, Mors O, Kruse TA. 1998b. Support for the possible locus on chromosome 4p16 for bipolar affective disorder.. Mol. Psychiatry 3:442–48 [Google Scholar]
  51. Ewald H, Mors O, Flint T, Koed K, Eiberg H, Kruse TA. 1995. A possible locus for manic depressive illness on chromosome 16p13.. Psychiatr. Genet. 5:71–81 [Google Scholar]
  52. Faraone SV, Matise T, Svrakic D, Pepple J, Malaspina D. et al. 1998. Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.. Am. J. Med. Genet. 81:290–95 [Google Scholar]
  53. Fava M, Kendler KS. 2000. Major depressive disorder.. Neuron 28:335–41 [Google Scholar]
  54. Fisher SE, Vargha-Khadem F, Watkins KE, Monaco AP, Pembrey ME. 1998. Localisation of a gene implicated in a severe speech and language disorder.. Nat. Genet. 18:168–70 [Google Scholar]
  55. Folstein S, Rutter M. 1977. Infantile autism: a genetic study of 21 twin pairs.. J. Child Psychol. Psychiatry 18:297–321 [Google Scholar]
  56. Freimer NB, Reus VI, Escamilla MA, McInnes LA, Spesny M. et al. 1996. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.. Nat. Genet. 12:436–41 [Google Scholar]
  57. Friddle C, Koskela R, Ranade K, Hebert J, Cargill M. et al. 2000. Full-genome scan for linkage in 50 families segregating the bipolar affective disease phenotype.. Am. J. Hum. Genet. 66:205–15 [Google Scholar]
  58. Fuster JM. 2000. Prefrontal neurons in networks of executive memory.. Brain Res. Bull. 52:331–36 [Google Scholar]
  59. Gejman PV, Detera-Wadleigh S, Martinez MM, Berrettini WH, Goldin LR. et al. 1990. Manic depressive illness not linked to factor IX region in an independent series of pedigrees.. Genomics 8:648–55 [Google Scholar]
  60. Goldman-Rakic PS. 1994. Working memory dysfunction in schizophrenia.. J. Neuropsychiatry Clin. Neurosci. 6:348–57 [Google Scholar]
  61. Gottesman II. 1991. Schizophrenia Genesis: The Origins of Madness. New York: Freeman [Google Scholar]
  62. Hallmayer J, Hebert JM, Spiker D, Lotspeich L, McMahon WM. et al. 1996. Autism and the X chromosome.. Multipoint sib-pair analysis Arch. Gen. Psychiatry 53:985–89 [Google Scholar]
  63. Harrison PJ. 1999. The neuropathology of schizophrenia.. A critical review of the data and their interpretation Brain 122(Pt 4):593–624 [Google Scholar]
  64. Hauser ER, Boehnke M, Guo SW, Risch N. 1996. Affected-sib-pair interval mapping and exclusion for complex genetic traits: sampling considerations.. Genet. Epidemiol. 13:117–37 [Google Scholar]
  65. Hovatta I, Varilo T, Suvisaari J, Terwilliger JD, Ollikainen V. et al. 1999. A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci.. Am. J. Hum. Genet. 65:1114–24 [Google Scholar]
  66. Hyman SE. 1999. The neurobiology of mental disorders. In The Harvard Guide to Psychiatry, ed. AM Nicholi 134–54 Cambridge, MA: Harvard Univ. Press [Google Scholar]
  67. Hyman SE. 2000. Mental illness: genetically complex disorders of neural circuitry and neural communication.. Neuron 28:321–23 [Google Scholar]
  68. International Molecular Genetic Study of Autism Consortium. 1998. A full genome screen for autism with evidence for linkage to a region on chromosome 7q.. Hum. Mol. Genet. 7:571–78 [Google Scholar]
  69. International Molecular Genetic Study of Autism Consortium. 2001. A genome wide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p.. Am. J. Hum. Genet. 69:570–81 [Google Scholar]
  70. Jensen J, Coon H, Hoff M, Rosenthal J, Reimherr F. et al. 1998. Search for a schizophrenia susceptibility gene on chromosome 13.. Psychiatr. Genet. 8:239–43 [Google Scholar]
  71. Kallman FJ. 1938. The Genetics of Schizophrenia. Locust Valley, NY: J. J. Augustin [Google Scholar]
  72. Kalsi G, Chen CH, Smyth C. 1996. Genetic analysis in an Icelandic/British sample fails to exclude the putative chromosome 13q14.1-q32 schizophrenia susceptibility locus.. Am. J. Hum. Genet. 59:A388 [Google Scholar]
  73. Karayiorgou M, Gogos JA, Galke BL, Wolyniec PS, Nestadt G. et al. 1998. Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility.. Biol. Psychiatry 43:425–31 [Google Scholar]
  74. Kelsoe JR, Ginns EI, Egeland JA, Gerhard DS, Goldstein AM. et al. 1989. Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish.. Nature 342:238–43 [Google Scholar]
  75. Kelsoe JR, Spence MA, Loetscher E, Foguet M, Sadovnick AD. et al. 2001. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22.. Proc. Natl. Acad. Sci. USA 98:585–90 [Google Scholar]
  76. Kendler KS, Gruenberg AM. 1984. An independent analysis of the Danish Adoption Study of Schizophrenia.. VI. The relationship between psychiatric disorders as defined by DSM-III in the relatives and adoptees Arch. Gen. Psychiatry 41:555–64 [Google Scholar]
  77. Kendler KS, MacLean CJ, O'Neill FA, Burke J, Murphy B. et al. 1996. Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.. Am. J. Psychiatry 153:1534–40 [Google Scholar]
  78. Kendler KS, Tsuang MT, Hays P. 1987. Age at onset in schizophrenia.. A familial perspective Arch. Gen. Psychiatry 44:881–90 [Google Scholar]
  79. Kety SS, Rosenthal D, Wender PH, Schulsinger F, Jacobsen B. 1976. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic.. Behav. Genet. 6:219–25 [Google Scholar]
  80. Knowles JA, Rao PA, Cox-Matise T, Loth JE, de Jesus GM. et al. 1998. No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees.. Am. J. Hum. Genet. 62:916–24 [Google Scholar]
  81. Kruglyak L, Daly MJ, Reeve-Daly MP, Lander ES. 1996. Parametric and nonparametric linkage analysis: a unified multipoint approach.. Am. J. Hum. Genet. 58:1347–63 [Google Scholar]
  82. Lachman HM, Kelsoe JR, Remick RA, Sadovnick AD, Rapaport MH. et al. 1997. Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22.. Am. J. Med. Genet. 74:121–28 [Google Scholar]
  83. Lamb JA, Moore J, Bailey A, Monaco AP. 2000. Autism: recent molecular genetic advances.. Hum. Mol. Genet. 9:861–68 [Google Scholar]
  84. Lander E, Kruglyak L. 1995. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.. Nat. Genet. 11:241–47 [Google Scholar]
  85. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC. et al. 2001. Initial sequencing and analysis of the human genome.. Nature 409:860–921 [Google Scholar]
  86. Lasseter VK, Pulver AE, Wolyniec PS, Nestadt G, Meyers D. et al. 1995. Follow-up report of potential linkage for schizophrenia on chromosome 22q: part 3.. Am. J. Med. Genet. 60:172–73 [Google Scholar]
  87. Leonard S, Gault J, Moore T, Hopkins J, Robinson M. et al. 1998. Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative.. Am. J. Med. Genet. 81:308–12 [Google Scholar]
  88. Levinson DF, Mahtani MM, Nancarrow DJ, Brown DM, Kruglyak L. et al. 1998. Genome scan of schizophrenia.. Am. J. Psychiatry 155:741–50 [Google Scholar]
  89. Lijam N, Paylor R, McDonald MP, Crawley JN, Deng CX. et al. 1997. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1.. Cell 90:895–905 [Google Scholar]
  90. Lin MW, Curtis D, Williams N, Arranz M, Nanko S. et al. 1995. Suggestive evidence for linkage of schizophrenia to markers on chromosome 13q14.1-q32.. Psychiatr. Genet. 5:117–26 [Google Scholar]
  91. Lin JP, Bale SJ. 1997. Parental transmission and D18S37 allele sharing in bipolar affective disorder.. Genet. Epidemiol. 14:665–68 [Google Scholar]
  92. Lin MW, Sham P, Hwu HG, Collier D, Murray R, Powell JF. 1997. Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations.. Hum. Genet. 99:417–20 [Google Scholar]
  93. Liu J, Nyholt DR, Magnussen P, Parano E, Pavone P. et al. 2001. A genomewide screen for autism susceptibility loci.. Am. J. Hum. Genet. 69:327–40 [Google Scholar]
  94. Martinez M, Goldin LR, Cao Q, Zhang J, Sanders AR. et al. 1999. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q.. Am. J. Med. Genet. 88:337–43 [Google Scholar]
  95. McInnes LA, Escamilla MA, Service SK, Reus VI, Leon P. et al. 1996. A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.. Proc. Natl. Acad. Sci. USA 93:13060–65 [Google Scholar]
  96. McMahon FJ, Hopkins PJ, Xu J, McInnis MG, Shaw S. et al. 1997. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series.. Am. J. Hum. Genet. 61:1397–404 [Google Scholar]
  97. Mendlewicz J, Linkowski P, Guroff JJ, Van Praag HM. 1979. Color blindness linkage to bipolar manic-depressive illness.. New evidence Arch. Gen. Psychiatry 36:1442–47 [Google Scholar]
  98. Mendlewicz J, Linkowski P, Wilmotte J. 1980. Linkage between glucose-6-phosphate dehydrogenase deficiency and manic-depressive psychosis.. Br. J. Psychiatry 137:337–42 [Google Scholar]
  99. Mendlewicz J, Simon P, Sevy S, Charon F, Brocas H. et al. 1987. Polymorphic DNA marker on X chromosome and manic depression.. Lancet 1:1230–32 [Google Scholar]
  100. Michaud CM, Murray CJ, Bloom BR. 2001. Burden of disease-implications for future research.. JAMA 285:535–39 [Google Scholar]
  101. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS. et al. 2000. Disruption of two novel genes by a translocation co-segregating with schizophrenia.. Hum. Mol. Genet. 9:1415–23 [Google Scholar]
  102. Mirnics K, Middleton FA, Marquez A, Lewis DA, Levitt P. 2000. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex.. Neuron 28:53–67 [Google Scholar]
  103. Moises HW, Yang L, Kristbjarnarson H, Wiese C, Byerley W. et al. 1995. An international two-stage genome-wide search for schizophrenia susceptibility genes.. Nat. Genet. 11:321–24 [Google Scholar]
  104. Morissette J, Villeneuve A, Bordeleau L, Rochette D, Laberge C. et al. 1999. Genome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in Quebec points to a locus of major effect on chromosome 12q23-q24.. Am. J. Med. Genet. 88:567–87 [Google Scholar]
  105. Murphy KC, Jones LA, Owen MJ. 1999. High rates of schizophrenia in adults with velo-cardio-facial syndrome.. Arch. Gen. Psychiatry 56:940–45 [Google Scholar]
  106. Murray CJL, Lopez AD. 1996. The Global Burden of Disease. Cambridge, MA: Harvard Univ. Press [Google Scholar]
  107. Nothen MM, Cichon S, Rohleder H, Hemmer S, Franzek E. et al. 1999. Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families.. Mol. Psychiatry 4:76–84 [Google Scholar]
  108. Nurnberger JI Jr, DePaulo JR, Gershon ES, Reich T, Blehar MC. et al. 1997. Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a preliminary report.. Am. J. Med. Genet. 74:227–37 [Google Scholar]
  109. Ostrander EA, Stanford JL. 2000. Genetics of prostate cancer: too many loci, too few genes.. Am. J. Hum. Genet. 67:1367–75 [Google Scholar]
  110. Pekkarinen P, Terwilliger J, Bredbacka PE, Lonnqvist J, Peltonen L. 1995. Evidence of a predisposing locus to bipolar disorder on Xq24-q27.1 in an extended Finnish pedigree.. Genome Res. 5:105–15 [Google Scholar]
  111. Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M. et al. 1999. Genome-wide scan for autism susceptibility genes.. Paris Autism Res. Int. Sibpair Study Hum. Mol. Genet. 8:805–12 [Google Scholar]
  112. Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A. et al. 1995. Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error: a twin and family history study of autism.. Am. J. Hum. Genet. 57:717–26 [Google Scholar]
  113. Polymeropoulos MH, Coon H, Byerley W, Gershon ES, Goldin L. et al. 1994. Search for a schizophrenia susceptibility locus on human chromosome 22.. Am. J. Med. Genet. 54:93–99 [Google Scholar]
  114. Price DL, Wong PC, Markowska AL, Lee MK, Thinakaren G. et al. 2000. The value of transgenic models for the study of neurodegenerative diseases.. Ann. NY Acad. Sci. 920:179–91 [Google Scholar]
  115. Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L. et al. 1994. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: part 1.. Am. J. Med. Genet. 54:36–43 [Google Scholar]
  116. Pulver AE, Mulle J, Nestadt G, Swartz KL, Blouin JL. et al. 2000. Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes.. Mol. Psychiatry 5:650–53 [Google Scholar]
  117. Repetto GM, White LM, Bader PJ, Johnson D, Knoll JH. 1998. Interstitial duplications of chromosome region 15q11q13: clinical and molecular characterization.. Am. J. Med. Genet. 79:82–89 [Google Scholar]
  118. Riley BP, McGuffin P. 2000. Linkage and associated studies of schizophrenia.. Am. J. Med. Genet. 97:23–44 [Google Scholar]
  119. Risch N, Botstein D. 1996. A manic depressive history.. Nat. Genet. 12:351–53 [Google Scholar]
  120. Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D. et al. 1999. A genomic screen of autism: evidence for a multilocus etiology.. Am. J. Hum. Genet. 65:493–507 [Google Scholar]
  121. Robins E, Guze SB. 1970. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia.. Am. J. Psychiatry 126:983–87 [Google Scholar]
  122. Robins LN, Regier DA. 1991. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York: Free Press [Google Scholar]
  123. Sanders AR, Detera-Wadleigh SD, Gershon ES. 1999. Molecular genetics of mood disorders. In Neurobiology of Mental Illness 299–316 New York: Oxford Univ. Press [Google Scholar]
  124. Sasaki T, Billett E, Petronis A, Ying D, Parsons T. et al. 1996. Psychosis and genes with trinucleotide repeat polymorphism.. Hum. Genet. 97:244–46 [Google Scholar]
  125. Schwab SG, Albus M, Hallmayer J, Honig S, Borrmann M. et al. 1995. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.. Nat. Genet. 11:325–27 [Google Scholar]
  126. Schwab SG, Eckstein GN, Hallmayer J, Lerer B, Albus M. et al. 1997. Evidence suggestive of a locus on chromosome 5q31 contributing to susceptibility for schizophrenia in German and Israeli families by multipoint affected sib-pair linkage analysis.. Mol. Psychiatry 2:156–60 [Google Scholar]
  127. Schwab SG, Hallmayer J, Albus M, Lerer B, Eckstein GN. et al. 2000. A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6.. Mol. Psychiatry 5:638–49 [Google Scholar]
  128. Schwab SG, Hallmayer J, Albus M, Lerer B, Hanses C. et al. 1998a. Further evidence for a susceptibility locus on chromosome 10p14-p11 in 72 families with schizophrenia by nonparametric linkage analysis.. Am. J. Med. Genet. 81:302–7 [Google Scholar]
  129. Schwab SG, Hallmayer J, Lerer B, Albus M, Borrmann M. et al. 1998b. Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.. Am. J. Hum. Genet. 63:1139–52 [Google Scholar]
  130. Shahbazian MD, Zoghbi HY. 2001. Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations.. Curr. Opin. Neurol. 14:171–76 [Google Scholar]
  131. Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ. et al. 1998. A genome-wide search for schizophrenia susceptibility genes.. Am. J. Med. Genet. 81:364–76 [Google Scholar]
  132. Siddiqui MR, Meisner S, Tosh K, Balakrishnan K, Ghei S. et al. 2001. A major susceptibility locus for leprosy in India maps to chromosome 10p13.. Nat. Genet. 27:439–41 [Google Scholar]
  133. Silverman JM, Greenberg DA, Altstiel LD, Siever LJ, Mohs RC. et al. 1996. Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree.. Am. J. Med. Genet. 67:162–71 [Google Scholar]
  134. Sobell JL, Lind TJ, Hebrink DD, Heston LL, Sommer SS. 1997. Screening the monoamine oxidase B gene in 100 male patients with schizophrenia: a cluster of polymorphisms in African-Americans but lack of functionally significant sequence changes.. Am. J. Med. Genet. 74:44–49 [Google Scholar]
  135. Spurlock G, Williams J, McGuffin P, Aschauer HN, Lenzinger E. et al. 1998. European multicentre association study of schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms.. Am. J. Med. Genet. 81:24–28 [Google Scholar]
  136. Stine OC, McMahon FJ, Chen L, Xu J, Meyers DA. et al. 1997. Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.. Am. J. Med. Genet. 74:263–69 [Google Scholar]
  137. Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M. et al. 1995. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect.. Am. J. Hum. Genet. 57:1384–94 [Google Scholar]
  138. Stober G, Saar K, Ruschendorf F, Meyer J, Nurnberg G. et al. 2000. Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15.. Am. J. Hum. Genet. 67:1201–7 [Google Scholar]
  139. Straub RE, Lehner T, Luo Y, Loth JE, Shao W. et al. 1994. A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.. Nat. Genet. 8:291–96 [Google Scholar]
  140. Straub RE, MacLean CJ, Martin RB, Ma Y, Myakishev MV. et al. 1998. A schizophrenia locus may be located in region 10p15-p11.. Am. J. Med. Genet. 81:296–301 [Google Scholar]
  141. Straub RE, MacLean CJ, O'Neill FA, Burke J, Murphy B. et al. 1995. A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity.. Nat. Genet. 11:287–93 [Google Scholar]
  142. Straub RE, MacLean CJ, O'Neill FA, Walsh D, Kendler KS. 1997. Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families.. Mol. Psychiatry 2:148–55 [Google Scholar]
  143. Straub RE, Speer MC, Luo Y, Rojas K, Overhauser J. et al. 1993. A microsatellite genetic linkage map of human chromosome 18.. Genomics 15:48–56 [Google Scholar]
  144. Sullivan PF, Neale MC, Kendler KS. 2000. Genetic epidemiology of major depression: review and meta-analysis.. Am. J. Psychiatry 157:1552–62 [Google Scholar]
  145. Tsuang MT, Faraone SV. 1990. The Genetics of Mood Disorders. Baltimore, MD: Johns Hopkins Univ. Press [Google Scholar]
  146. US Dep. Health Hum. Serv. 1999. Mental Health: A Report of the Surgeon General. Rockville, MD: US Dep. Health Hum. Serv., NIH [Google Scholar]
  147. Veenstra-Vander Weele J, Gonen D, Leventhal BL, Cook EH Jr. 1999. Mutation screening of the UBE3A/E6-AP gene in autistic disorder.. Mol. Psychiatry 4:64–67 [Google Scholar]
  148. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ. et al. 2001. The sequence of the human genome.. Science 291:1304–51 [Google Scholar]
  149. Vincent JB, Herbrick JA, Gurling HM, Bolton PF, Roberts W, Scherer SW. 2000. Identification of a novel gene on chromosome 7q31 that is interrupted by a translocation breakpoint in an autistic individual.. Am. J. Hum. Genet. 67:510–14 [Google Scholar]
  150. Wassink TH, Piven J, Vieland VJ, Huang J, Swiderski RE. et al. 2001. Evidence supporting WNT2 as an autism susceptibility gene.. Am. J. Med. Genet. 105:406–13 [Google Scholar]
  151. Waterston R, Sulston JE. 1998. The Human Genome Project: reaching the finish line.. Science 282:53–54 [Google Scholar]
  152. Watson JD. 1990. The human genome project: past, present, and future.. Science 248:44–49 [Google Scholar]
  153. Weber JL, Myers EW. 1997. Human whole-genome shotgun sequencing.. Genome Res. 7:401–9 [Google Scholar]
  154. Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS. et al. 2001. Prefrontal neurons and the genetics of schizophrenia.. Biol. Psychiatry 50:825–44 [Google Scholar]
  155. Williams J, McGuffin P, Nothen M, Owen MJ. 1997. Meta-analysis of association between the 5-HT2a receptor T102C polymorphism and schizophrenia.. Eur. Multicent. Assoc. Study Schizophr. (EMASS) Group Lancet 349:1221 [Google Scholar]
  156. Williams J, Spurlock G, McGuffin P, Mallet J, Nothen MM. et al. 1996. Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene.. Eur. Multicent. Assoc. Study Schizophr. (EMASS) Group Lancet 347:1294–96 [Google Scholar]
  157. Wills C. 1991. The Science Behind the Human Genome Project. New York: Basic Books [Google Scholar]
  158. Winokur G, Clayton PJ, Reich T. 1969. Manic-Depressive Illness 112–25 St. Louis: CV Mosby
  159. Zoghbi HY, Orr HT. 2000. Glutamine repeats and neurodegeneration.. Annu. Rev. Neurosci. 23:217–47 [Google Scholar]
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