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Current Problems of Complex Disease Genes Mapping

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Genomic Architecture of Schizophrenia Across Diverse Genetic Isolates

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Abstract

Complex or multifactorial diseases are controlled by many factors, including both genes and the environment. Complex diseases are typically common, accounting for more than 90 % of human diseases, and are the (leading) causes of disability and premature death. The identification of susceptibility genes for complex diseases therefore has theoretical and practical importance, as they may facilitate the development of effective methods for diagnosis, treatment, and prevention.

The technologies and strategies used to detect genetic factors that influence the development of complex diseases have limitations (Scheuner et al., American Journal of Medical Genetics Part C: Seminars in Medical Genetics 125C:50–65, 2004). Genetic heterogeneity causes different genes to influence the development of similar clinical symptoms in clinically homogeneous patients. Factors such as changes in habitat and migration subdivide gene pools in populations containing mutant genes involved in the pathogenesis of complex diseases. The role of these factors in forming a specific gene pool within a local population is often difficult to determine, and therefore, they are referred to as random or stochastic. Onset and incidence of complex diseases, as well as the evolutionary features of specific populations, are affected when genetic and environmental factors interact. Additionally, ethnic and social heterogeneity within such outbred populations increases the effects of penetrance and phenocopies of complex diseases due to the diversity and dynamics of environmental factors. These interrelated factors make it difficult to obtain reliable results in mapping genes of complex diseases, and therefore, careful selection of populations to map these genes is required. However, the characteristics of gene pools of such populations are very seldom analyzed. When identifying genomic regions linked or associated with the mental illness, these difficulties often lead to results that are not always supported by researchers working with the same disease in other different human populations, which have a different gene pool and ethno-social environment. A study of a population’s gene pool developed during its particular demographic history is important because such gene pool defines a certain genetic architecture of complex traits (including diseases) among its members. Genetic isolates of indigenous ethnic groups provide exceptional opportunities for identifying genes of complex diseases. These communities are established by a small number of founders and have a stable total volume for hundreds of generations in an unchanging environment. Pioneering studies of Bulayeva et al. (1976–2011) of population genetics in indigenous ethnic groups of Dagestan and in neighboring regions revealed remote highland genetic isolates of different ethnicities with predominant aggregation of certain complex diseases.

The unique ethnic diversity and antiquity of the 26 indigenous populations are reflected in the features of the gene pool and the disease patterns in populations of these groups. Therefore, Dagestan is one of most effective regions in the world for gene mapping of complex diseases, including schizophrenia. Several studies identified genetic markers of schizophrenia spectrum disorders in a number of chromosomal regions. These results, however, are rarely reproduced by researchers working with different populations. In this regard, the main objective of our study was mapping genes of the same complex disease, diagnosed and genotyped by standardized methods, in ethnically and demographically subdivided genetic isolates.

In genetic isolates with distinct demographics and ethnicities, diagnosing and genotyping complex diseases using unified methods will establish mechanisms that determine intra- and interpopulation spectra of genomic linkages involved in the pathogenesis of the studied disease.

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References

  • Alda, M., Dvorakova, M., et al. (1989). Genetic aspects in chronic schizophrenia. Morbidity risks and contributory factors. Schizophrenia Research, 2, 339–344.

    Article  CAS  PubMed  Google Scholar 

  • Asherson, P., Walsh, C., Williams, J., Sargeant, M., Taylor, C., Clements, A., Gill, M., Owen, M., & McGuffin, P. (1994). Imprinting and anticipation. Are they relevant to genetic studies of schizophrenia? British Journal of Psychiatry, 164(5), 619–624.

    Article  CAS  PubMed  Google Scholar 

  • Asherson, P., Mant, R., Williams, N., Cardno, A., Jones, L., Murphy, K., Collier, D. A., Nanko, S., Craddock, N., Morris, S., Muir, W., Blackwood, B., McGuffin, P., & Owen, M. J. (1998). A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder. Molecular Psychiatry, 3(4), 310–320.

    Article  CAS  PubMed  Google Scholar 

  • Bennett, C., Crawford, F., et al. (1995). Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer’s disease but is not causative. AJMG (Neuropsychiatric Genetics), 60, 1–6.

    Article  CAS  Google Scholar 

  • Bertolino, A., Knable, M. B., Saunders, R. C., Callicott, J. H., Kolachana, B., Mattay, V. S., Bachevalier, J., Frank, J. A., Egan, M., & Weinberger, D. R. (1999). The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia. Biological Psychiatry, 45(6), 660–667.

    Article  CAS  PubMed  Google Scholar 

  • Blackwood, S. K., MacHale, S. M., Power, M. J., Goodwin, G. M., & Lawrie, S. M. (1998). Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. Journal of Neurology, Neurosurgery and Psychiatry, 65, 541–546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blackwood, D., Fordyce, A., & Walker, M., et al. (2001). Schizophrenia and affective disorders—Cosegregation with a translocation at chromosome 1q42. That directly disrupts brain-expressed genes: Clinical and P300 findings in a family. American Journal of Human Genetics, (69), 428–433.

    Google Scholar 

  • Blakely, R. D. (2001). Dopamine’s reversal of fortune. Science, 293, 2407–2408.

    Article  CAS  PubMed  Google Scholar 

  • Blouin, J. L., Dombroski, B. A., et al. (1998). Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21. Nature Genetics, 20, 70–73.

    Article  CAS  PubMed  Google Scholar 

  • Boehnke, M. (2000). A look at linkage disequilibrium. Nature Genetics, 25, 246–247.

    Article  CAS  PubMed  Google Scholar 

  • Bolin, S. R., Stoffregen, W. C., Nayar, G. P. S., & Hamel, A. L. (2001). Postweaning multisystemic wasting syndrome induced after experimental inoculation of cesarean-derived, colostrum-deprived piglets with type 2 porcine circovirus. Journal of Veterinary Diagnostic Investigation, 13, 185–194.

    Article  CAS  PubMed  Google Scholar 

  • Boutros, N., Zouridakis, G., et al. (1993). The P50 component of the auditory evoked potential and subtypes of schizophrenia. Psychiatry Research, 47, 243–254.

    Article  CAS  PubMed  Google Scholar 

  • Bray, N., & Owen, M. (2001). Searching for schizophrenia genes. Trends in Molecular Medicine, 7(4), 169–174.

    Article  CAS  PubMed  Google Scholar 

  • Brzustowicz, L. M., Hodgkinson, K., et al. (2000). Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science, 288, 678–682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brzustowicz, L. M., Honer, W. G., Chow, E. W., et al. (1999). Linkage of familial schizophrenia to chromosome 13q32. The American Journal of Human Genetics, 65(4), 1096–1103.

    Article  CAS  PubMed  Google Scholar 

  • Buetow, K. H., Ludwigsen, S., Scherpbier-Heddema, T., et al. (1994). Human genetic map. Genome maps V. Wall chart. Science, 265(5181), 2055–2070.

    Article  CAS  PubMed  Google Scholar 

  • Bulayeva, K. B., Leal, S. M., Pavlova, T. A., et al. (2005). Mapping genes of complex psychiatric diseases in Daghestan genetic isolates. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 132(1), 76–84.

    Article  Google Scholar 

  • Bulayeva, K. B., Pavlova, T. A., Kurbanov, R. M., & Bulayev, O. A. (2002). Mapping genes of complex disease in genetic isolates of Dagestan. Journal of Genetics (Russia), 38(11), 1539–1548.

    Google Scholar 

  • Cardino, A. G., Bowen, T., et al. (1999). CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia. Society of Biological Psychiatry, 45(12), 1592–1596.

    Article  Google Scholar 

  • Cardno, A. G., Murphy, K. C., et al. (1996). Expanded CAG/CTG repeats in schizophrenia a study of clinical correlates. British Journal of Psychiatry, 169, 766–771.

    Article  CAS  PubMed  Google Scholar 

  • Carlsson, A. (1988). The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology, 1(3), 179–203.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C. H., Liu, M. Y., Wei, F. C., Koong, F. J., Hwu, H. G., & Hsiao, K. J. (1997). Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia. American Journal of Medical Genetics, 74(1), 40–43.

    Article  CAS  PubMed  Google Scholar 

  • Cichon, S., Nothen, M. M., Erdmann, J., & Propping, P. (1994). Detection of four polymorphic sites in the human dopamine D1 receptor gene (DRD1). Human Molecular Genetics, 3, 209.

    Article  CAS  PubMed  Google Scholar 

  • Clementz, B. A., Geyer, M. A., et al. (1998). Poor p50 suppression among schizophrenia patients and their first-degree biological relatives. American Journal of Psychiatry, 155, 1691–1694.

    Article  CAS  PubMed  Google Scholar 

  • Cloninger, C. R., Kaufman, C. A., et al. (1998). A genome-wide search for schizophrenia susceptibility loci: The NIMH genetics initiative and Millennium consortium. American Journal of Medical Genetics (Neuropsychiatric Genetics), 81, 275–281.

    Article  CAS  Google Scholar 

  • Cohen, B. M., Ennulat, D. J., et al. (1999). Polymorphisms of the dopamine D4 receptor and response to antipsychotic drugs. Psychopharmacology, 141, 6–10.

    Article  CAS  PubMed  Google Scholar 

  • Conneally, P. M. (1991). Association between the D2 dopamine receptor gene and alcoholism. A continuing controversy. Archives of General Psychiatry, 48(8), 757–759.

    Article  CAS  PubMed  Google Scholar 

  • Cravchik, A., & Goldman, D. (2000). Neurochemical individuality: Genetic diversity among human dopamine and serotonin receptors and transporters. Archives of General Psychiatry, 57, 1105–1114.

    Article  CAS  PubMed  Google Scholar 

  • Crocq, M. A., Mant, R., Asherson, P., Williams, J., Hode, Y., Mayerova, A., Collier, D., Lannfelt, L., Sokoloff, P., Schwartz, J. C., et al. (1992). Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. Journal of Medical Genetics, 29(12), 858–860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crowe, R. R., Wang, Z., Noyes, R., Jr., Albrecht, B. E., Darlison, M. G., Bailey, M. E., Johnson, K. J., & Zoëga, T. (1997). Candidate gene study of eight GABAA receptor subunits in panic disorder. American Journal of Psychiatry, 154(8), 1096–1100.

    Article  CAS  PubMed  Google Scholar 

  • Davis, K. L., Kahn, R. S., et al. (1991). Dopamine in schizophrenia: A review and reconceptualization. American Journal of Psychiatry, 148(11), 1474–1486.

    Article  CAS  PubMed  Google Scholar 

  • De Luca, A., Pasini, A., Amati, F., Botta, A., Spalletta, G., Alimenti, S., Caccamo, F., Conti, E., Trakalo, J., Macciardi, F., Dallapiccola, B., & Novelli, G. (2001). Association study of a promoter polymorphism of UFD1L gene with schizophrenia. American Journal of Medical Genetics, 105(6), 529–533.

    Article  PubMed  Google Scholar 

  • Devlin, B., Bacanu, S. A., Roeder, K., Reimherr, F., Wender, P., Galke, B., Novasad, D., Chu, A., TCuenco, K., Tiobek, S., Otto, C., & Byerley, W. (2002). Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from the oceanic nation of Palau. Molecular Psychiatry, 7(7), 689–694.

    Article  CAS  PubMed  Google Scholar 

  • Devon, R. S., Evans, K. L., Maule, J. C., Christie, S., Anderson, S., Brown, J., Shibasaki, Y., Porteous, D. J., & Brookes, A. J. (1997). Novel transcribed sequences neighbouring a translocation breakpoint associated with schizophrenia. American Journal of Medical Genetics, 74(1), 82–90.

    Article  CAS  PubMed  Google Scholar 

  • Devon, R. S., & Porteous, D. J. (1997). Physical mapping of a glutamate receptor gene in relation to a balanced translocation associated with schizophrenia in a large Scottish family. Psychiatric Genetics, 7(4), 165–169.

    Article  CAS  PubMed  Google Scholar 

  • Ebstein, R. P., Segman, R., et al. (1997). 5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: Interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms. American Journal of Medical Genetics, 74(1), 65–72.

    Article  CAS  PubMed  Google Scholar 

  • Ekelund, J., Lichtermann, D., Järvelin, M. R., & Peltonen, L. (1999). Association between novelty-seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample. American Journal of Psychiatry, 156(9), 1453–1455.

    CAS  PubMed  Google Scholar 

  • Erdman, J., Shimron-Abarbanell, D., Rietschel, M., et al. (1996). Systematic screening for mutations in the human serotonin 2A (5HT2A) receptor gene identification of two naturally occurring receptor variants and association analysis in schizophrenia. Human Genetics, 97(5), 614–619.

    Article  Google Scholar 

  • Falconer, D. S. (1960). Introduction to quantitative genetics (p. 365). London: Longman Group Ltd.

    Google Scholar 

  • Fallin, D., Reading, S., et al. (1997). No interaction between the APOE and the alpha-1-antichymotrypsin genes on risk for Alzheimer’s disease. American Journal of Medical Genetics, 74, 192–194.

    Article  CAS  PubMed  Google Scholar 

  • Fan, J. B., Tang, J. X., Gu, N. F., et al. (2002). A family-based and case-control association study of the NOTCH4 gene and schizophrenia. Molecular Psychiatry, 7, 100–103.

    Article  CAS  PubMed  Google Scholar 

  • Faraone, S. V., Doyle, A. E., Mick, E., & Biederman, J. (2001). Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. American Journal of Psychiatry, 158(7), 1052–1057.

    Article  CAS  PubMed  Google Scholar 

  • Faraone, S. V., Matise, T., Svrakic, D., Pepple, J., Malaspina, D., Suarez, B., Hampe, C., Zambuto, C. T., Schmitt, K., Meyer, J., Markel, P., Lee, H., Harkavy Friedman, J., Kaufmann, C., Cloninger, C. R., & Tsuang, M. T. (1998). Genome scan of European-American schizophrenia pedigrees: Results of the NIMH Genetics Initiative and Millennium Consortium. American Journal of Medical Genetics, 81(4), 290–295.

    Article  CAS  PubMed  Google Scholar 

  • Faraone, S. V., Meyer, J., et al. (1999). Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion. American Journal of Medical Genetics, 88, 607–608.

    Article  CAS  PubMed  Google Scholar 

  • Freedman, R., Coon, H., Myles-Worsley, M., Orr-Urtreger, A., Olincy, A., Davis, A., Polymeropoulos, M., Holik, J., Hopkins, J., Hoff, M., Rosenthal, J., Waldo, M. C., Reimherr, F., Wender, P., Yaw, J., Young, D. A., Breese, C. R., Adams, C., Patterson, D., Adler, L. E., Kruglyak, L., Leonard, S., & Byerley, W. (1997). Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences of the United States of America, 94(2), 587–592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freedman, R., Leonard, S., Olincy, A., et al. (2001). Evidence for the multigenic inheritance of schizophrenia. American Journal of Medical Genetics, 105(8), 794–800.

    Article  CAS  PubMed  Google Scholar 

  • Garbutt, J. C., & van Kammen, D. P. (1983). The interaction between GABA and dopamine: Implications for schizophrenia. Schizophrenia Bulletin, 9(3), 336–353.

    Article  CAS  PubMed  Google Scholar 

  • Gejman, P. V., Ram, A., Gelernter, J., Friedman, E., Cao, Q., Pickar, D., Blum, K., Noble, E. P., Kranzler, H. R., O’Malley, S., et al. (1994). No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. JAMA, 271(3), 204–208.

    Article  CAS  PubMed  Google Scholar 

  • Gill, M., McGuffin, P., et al. (1993). A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11. Psychological Medicine, 23(1), 27–44.

    Article  CAS  PubMed  Google Scholar 

  • Glatt, S. J., Wang, R. S., Yeh, Y. C., Tsuang, M. T., & Faraone, S. V. (2005). Five NOTCH4 polymorphisms show weak evidence for association with schizophrenia: Evidence from meta-analyses. Schizophrenia Research, 73(2–3), 281–290.

    Article  PubMed  Google Scholar 

  • Gottesman, I. I. (1991). Schizophrenia genesis: The origins of madness (p. 296). WH Freeman/Times Books/Henry Holt & Co.

    Google Scholar 

  • Gottesman, I. I., & Shields, J. (1972). Schizophrenia and genetics, a Twin study vantage point. New York, London: Academic Press.

    Google Scholar 

  • Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160(4), 636–645.

    Article  PubMed  Google Scholar 

  • Grandy, D. K., Zhou, Q. Y., Allen, L., Litt, R., Magenis, R. E., Civelli, O., & Litt, M. (1990). A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and identifies an EcoRIRFLP. American Journal of Human Genetics, 47(5), 828–834.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gur, R. E., Cowell, P. E., et al. (2000). Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Archives of General Psychiatry, 57, 761–768.

    Article  CAS  PubMed  Google Scholar 

  • Gurling, H. M., Kalsi, G., Brynjolfson, J., et al. (2001). Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. The American Journal of Human Genetics, 68(3), 661–673.

    Article  CAS  PubMed  Google Scholar 

  • Hastbacka, J., de la Chapelle, A., & Mahtani, M. M. (1994). The diastrophic dysplasia gene encodes a novel sulfate transporter: Positional cloning by fine-structure linkage disequilibrium mapping. Cell, 78(6), 1073–1087.

    Article  CAS  PubMed  Google Scholar 

  • Hawi, Z., Myakishev, M. V., Straub, R. E., O’Neill, A., Kendler, K. S., Walsh, D., & Gill, M. (1997). No association or linkage between the 5-HT2a/T102C polymorphism and schizophrenia in Irish families. American Journal of Medical Genetics, 74(4), 370–373.

    Article  CAS  PubMed  Google Scholar 

  • Heils, A., Teufel, A., Petri, S., Stober, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66, 2621–2624.

    Article  CAS  PubMed  Google Scholar 

  • Herken, H., & Erdal, M. E. (2001). Catechol-O-methyltransferase gene polymorphism in schizophrenia: Evidence for association between symptomatology and prognosis. Journal of Psychiatric Genetics, 11(2), 105–109.

    Article  CAS  PubMed  Google Scholar 

  • Hill, S. Y., Locke, J., Zezza, N., Kaplan, B., Neiswanger, K., Steinhauer, S. R., Wipprecht, G., & Xu, J. (1998). Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism. Biological Psychiatry, 43(1), 40–51.

    Article  CAS  PubMed  Google Scholar 

  • Hovatta, L., Varilo, T., Suvisaari, J., Terwilliger, J., et al. (1999). A genomewide screen for schizophrenia genes in an isolated finnish subpopulation, suggesting multiple susceptibility loci. The American Journal of Human Genetics, 65(4), 1114–1124.

    Article  CAS  PubMed  Google Scholar 

  • Hranilovic, D., Schwab, S. G., Jernej, B., Knapp, M., Lerer, B., Albus, M., et al. (2000). Serotonin transporter gene and schizophrenia: Evidence for association/linkage disequilibrium in families with affected siblings. Molecular Psychiatry, 5, 91–95. doi:10.1038/sj.mp.4000599.

    Article  CAS  PubMed  Google Scholar 

  • Illarioshkin, S. N., Ivanova-Smolenskaya, I. A., et al. (1996). Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy. Brain, 119, 1895–1909.

    Article  PubMed  Google Scholar 

  • Imai, Y., Gates, M. A., Melby, A. E., Kimelman, D., Schier, A. F., & Talbot, W. S. (2001). The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish. Development, 128(12), 2407–2420.

    CAS  PubMed  Google Scholar 

  • Jacobsen, L. K., Staley, J. K., et al. (2000). Prediction of dopamine transporter binding availability by genotype: A preliminary report. American Journal of Psychiatry, 157(10), 1700–1703.

    Article  CAS  PubMed  Google Scholar 

  • Jaskiw, G. E., & Weinberger, D. R. (1992). Dopamine and schizophrenia—A cortically corrective perspective. The Neurosciences, 4, 179–188.

    Google Scholar 

  • Jönsson, E., Lannfelt, L., Sokoloff, P., Schwartz, J. C., & Sedvall, G. (1993). Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. Acta Psychiatrica Scandinavica, 87(5), 345–349.

    Article  PubMed  Google Scholar 

  • Jorde, L. B. (2000). Linkage disequilibrium and the search for complex disease genes. Genome Research, 10(10), 1435–1444.

    Article  CAS  PubMed  Google Scholar 

  • Kalsi, G., Mankoo, B., Curtis, D., Sherrington, R., Melmer, G., Brynjolfsson, J., Sigmundsson, T., Read, T., Murphy, P., Petursson, H., & Gurling, H. (1999). New DNA markers with increased informativeness show diminished support for a chromosome 5q11-13 schizophrenia susceptibility locus and exclude linkage in two new cohorts of British and Icelandic families. Annals of Human Genetics, 63(Pt 3), 235–247.

    Article  CAS  PubMed  Google Scholar 

  • Kapur, S., & Remington, G. (1996). Serotonin-Dopamine interaction and its relevance to schizophrenia. American Journal of Psychiatry, 153(4), 466–476.

    Article  CAS  PubMed  Google Scholar 

  • Kapur, A., & Seeman, A. (2001). Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics? A new hypothesis. American Journal of Psychiatry, 158(3), 360–369.

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann, C. A., Suarez, B., et al. (1998). The NIMH genetics initiative Millennium schizophrenia consortium: Linkage analysis of African-American pedigrees. The Journal of Medical Genetics (Neuropsychiatric Genetics), 81, 282–289.

    Article  CAS  Google Scholar 

  • Kebabian, J. W., Beaulieu, M., & Itoh, Y. (1984). Pharmacological and biochemical evidence for the existence of two categories of dopamine receptor. The Canadian Journal of Neurological Sciences, 1, 114–117.

    Article  Google Scholar 

  • Kendler, K. S., MacLean, C. J., O’Neill, F. A., et al. (1996). Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish study of high-density schizophrenia families. American Journal of Psychiatry, 153, 1534–1540.

    Article  CAS  PubMed  Google Scholar 

  • Kendler, K. S., Myers, J. M., et al. (2000). Clinical features of schizophrenia and linkage to chromosomes 5q, 6p, 8p, and 10p in the Irish study of high-density schizophrenia families. American Journal of Psychiatry, 157(3), 402–408.

    Article  CAS  PubMed  Google Scholar 

  • King, N., Bassett, A. S., Honer, W. G., et al. (1997). Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families. American Journal of Medical Genetics, 74, 472–474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knight, J. (1983). Dopamine-receptor-stimulating autoantibodies: A possible cause of schizophrenia. The Lancet (Nov. 13, 1982), 1073–1075.

    Google Scholar 

  • Koishi, S., Yamazaki, K., Yamamoto, K., Koishi, S., Enseki, Y., Nakamura, Y., Oya, A., Yasueda, M., Asakura, A., Aoki, Y., Atsumi, M., Inomata, J., Inoko, H., & Matsumoto, H. (2004). Notch4 gene polymorphisms are not associated with autism in Japanese population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 125B(1), 61–62.

    Article  Google Scholar 

  • Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402(6762), 656–660.

    Article  CAS  PubMed  Google Scholar 

  • Kosower, N. S., Gerad, L., Goldstein, M., et al. (1995). Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia. American Journal of Medical Genetics, 60, 133–138.

    Article  CAS  PubMed  Google Scholar 

  • Kouzmenko, A. P., Scaffidi, A., Pereira, A. M., Hayes, W. L., Copolov, D. L., & Dean, B. (1999). No correlation between A(-1438)G polymorphism in 5-HT2A receptor gene promoter and thedensity of frontal cortical 5-HT2A receptors in schizophrenia. Human Heredity, 49(2), 103–105.

    Article  CAS  PubMed  Google Scholar 

  • Kruglyak, L. (1999). Genetic isolates: Separate but equal? Proceedings of the National Academy of Sciences of the United States of America, 96(4), 1170–1172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kukull, W. A., & Martin, G. M. (1998). Editorials: APOE polymorphisms and late-onset Alzheimer disease. Journal of the American Medical Association, 279(10), 788–789.

    Article  CAS  PubMed  Google Scholar 

  • Lawrie, S. M., Whalley, H. C., Abukmeil, S. S., et al. (2001). Brain structure, genetic liability and psychotic symptoms in subjects at high risk of developing schizophrenia. Biological Psychiatry, 49, 811–823.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. F., Lu, R. B., Ko, H. C., et al. (1999). No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcoholism: Clinical and Experimental Research, 23(4), 592–599.

    Article  CAS  Google Scholar 

  • Levinson, D. F. (2003). Molecular genetics of schizophrenia: Review of the recent literature. Current Opinion in Psychiatry, 16, 157–170.

    Article  Google Scholar 

  • Levinson, D. F., Holmans, P. A., et al. (2002). No major schizophrenia locus detected on chromosome 1q in a large multicenter sample. Science, 296, 739–741.

    Article  CAS  PubMed  Google Scholar 

  • Levinson, D. F., Mahtani, M. M., et al. (1998). Genome scan of schizophrenia. American Journal of Psychiatry, 155(6), 741–750.

    CAS  PubMed  Google Scholar 

  • Lin, C., Hsiao, C., & Chen, W. (1999). Development of sustained attention assessed using the continuous performance test among children 6–15 years of age. Journal of Abnormal Child Psychology, 27, 403–412.

    Article  CAS  PubMed  Google Scholar 

  • Litt, M., al-Dhalimy, M., Zhou, Q., Grandy, D., & Civelli, O. (1991). A TaqI RFLP at the DRD1 locus. Nucleic Acids Research, 19(11), 3161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, W. M., Mei, R., Di, X., Ryder, T. B., Hubbell, E., Dee, S., Webster, T. A., Harrington, C. A., Ho, M. H., Baid, J., & Smeekens, S. P. (2002). Analysis of high-density expression microarrays with signed-rank call algorithms. Bioinformatics, 18(12), 1593–1599.

    Article  CAS  PubMed  Google Scholar 

  • Liu, L. L., Wei, J., Zhang, X., Li, X. Y., Shen, Y., Liu, S. Z., Ju, G. Z., Shi, J. P., Yu, Y. Q., Xu, Q., & Hemmings, G. P. (2004). Lack of a genetic association between the TNXB locus and schizophrenia in a Chinese population. Neuroscience Letters, 355(1–2), 149–151.

    CAS  PubMed  Google Scholar 

  • Mant, R., Williams, J., Asherson, P., Parfitt, E., McGuffin, P., & Owen, M. J. (1994). Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. American Journal of Medical Genetics, 54(1), 21–26.

    Article  CAS  PubMed  Google Scholar 

  • Maziade, M., Martinez, M., Rodrigue, C., Gauthier, B., Tremblay, G., Fournier, C., Bissonnette, L., Simard, C., Roy, M. A., Rouillard, E., & Mérette, C. (1997). Childhood/early adolescence-onset and adult-onset schizophrenia. Heterogeneity at the dopamine D3 receptor gene. The British Journal of Psychiatry, 170, 27–30.

    Article  CAS  PubMed  Google Scholar 

  • Maziade, M., Raymond, V., Cliche, D., Fournier, J. P., Caron, C., Garneau, Y., Nicole, L., Marcotte, P., Couture, C., Simard, C., et al. (1995). Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia. American Journal of Medical Genetics, 60(6), 522–528.

    Article  CAS  PubMed  Google Scholar 

  • McGinnis, R. E., Fox, H., Yates, P., et al. (2001). Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland. Nature Genetics, 28, 128–129.

    Article  CAS  PubMed  Google Scholar 

  • McGlashan, T. H., & Hoffman, R. E. (2000). Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Archives of General Psychiatry, 57(7), 637–648.

    Article  CAS  PubMed  Google Scholar 

  • McGuffin, P., & Owen, M. (1991). The molecular genetics of schizophrenia: An overview and forward view. European Archives of Psychiatry and Clinical Neuroscience, 240(3), 169–173.

    Article  CAS  PubMed  Google Scholar 

  • McNeil, T. F., Cantor-Graae, E., et al. (1993). Prenatal cerebral development in individuals at genetic risk for psychosis: Head size at birth in offspring of women with schizophrenia. Schizophrenia Research, 10(1), 1–5.

    Article  CAS  PubMed  Google Scholar 

  • Millar, J. K., Wilson-Annan, J. C., Anderson, S., et al. (2000). Disruption of two novel genes by a translocation co-segregating with schizophrenia. Human Molecular Genetics, 9, 1415–1423.

    Article  CAS  PubMed  Google Scholar 

  • Moises, H. W., Gelernter, J., et al. (1991). No linkage between D2 dopamine receptor gene region and schizophrenia. Archives of General Psychiatry, 48(7), 643–647.

    Article  CAS  PubMed  Google Scholar 

  • Moises, H. W., Yang, L., Krisbjanarson, H., et al. (1995). An international two-stage genome-wide search for schizophrenia susceptibility genes. Nature Genetics, 11, 321–324.

    Article  CAS  PubMed  Google Scholar 

  • Mulcrone, J., Whatley, S. A., Marchbanks, R., et al. (1995). Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees. American Journal of Medical Genetics, 60, 103–108.

    Article  CAS  PubMed  Google Scholar 

  • Nanko, S., Gill, M., Owen, M., Takazawa, N., Moridaira, J., & Kazamatsuri, H. (1992). Linkage study of schizophrenia with markers on chromosome 11 in two Japanese pedigrees. The Japanese Journal of Psychiatry and Neurology, 46(1), 155–159.

    CAS  PubMed  Google Scholar 

  • Nanko, S., Sasaki, T., Fukuda, R., Hattori, M., Dai, X. Y., Kazamatsuri, H., Kuwata, S., Juji, T., & Gill, M. (1993). A study of the association between schizophrenia and the dopamine D3 receptor gene. Human Genetics, 92(4), 336–338.

    Article  CAS  PubMed  Google Scholar 

  • Naylor, L., Dean, B., Pereira, A., Mackinnon, A., Kouzmenko, A., & Copolov, D. (1998). No association between the serotonin transporter-linked promoter region polymorphism and either schizophrenia or density of the serotonin transporter in human hippocampus. Molecular Medicine, 4(10), 671–674.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nimgaonkar, V. L., Zhang, X. R., Caldwell, J. G., Ganguli, R., & Chakravarti, A. (1993). Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: Probable effects of family history of schizophrenia? American Journal of Medical Genetics, 48(4), 214–217.

    Article  CAS  PubMed  Google Scholar 

  • Nimgaonkar, V. L., Zhang, X. R., Brar, J. S., DeLeo, M., & Ganguli, R. (1996, Spring). 5-HT2 receptor gene locus: Association with schizophrenia or treatment response not detected. Psychiatric Genetics, 6(1), 23–27.

    Google Scholar 

  • Norton, N., Kirov, G., Zammit, S., Jones, G., Jones, S., Owen, R., Krawczak, M., Williams, N. M., O’Donovan, M. C., & Owen, M. J. (2002). Schizophrenia and functional polymorphisms in the MAOA and COMT genes: No evidence for association or epistasis. American Journal of Medical Genetics, 114(5), 491–496.

    Article  PubMed  Google Scholar 

  • Nothen, M. M., Cichon, S., et al. (1993). Excess of homozygosis at the dopamine D3 receptor gene in schizophrenia not confirmed. Journal of Medical Genetics, 30(8), 708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nöthen, M. M., Erdmann, J., Shimron-Abarbanell, D., & Propping, P. (1994). Identification of genetic variation in the human serotonin 1D beta receptor gene. Biochemical and Biophysics Research Communications, 205(2), 1194–1200.

    Article  Google Scholar 

  • Oliveira, J. R., et al. (1998). The short variant of the polymorphism within the promoter region of the serotonin transporter gene is a risk factor for late onset Alzheimer’s disease. Molecular Psychiatry, 3, 438–441.

    Article  CAS  PubMed  Google Scholar 

  • Owen, M. J., Cardno, A. G., & O’Donovan, M. C. (2000). Psychiatric genetics: Back to the future. Molecular Psychiatry, 5(1), 22–31.

    Article  CAS  PubMed  Google Scholar 

  • Paunio, T., Ekelund, J., Hovatta, I., et al. (2000). Genome wide scan of an extended Finnish schizophrenia study sample. American Journal of Medical Genetics, 96, 460.

    Article  Google Scholar 

  • Peltonen, L. (2000). Positional cloning of disease genes: Advantages of genetic isolates. Human Heredity, 50(1), 66–75.

    Article  CAS  PubMed  Google Scholar 

  • Prasad, S., Deshpande, S. N., Bhatia, T., Wood, J., Nimgaonkar, V. L., & Thelma, B. K. (1999). Association study of schizophrenia among Indian families. American Journal of Medical Genetics, 88(4), 298–300.

    Article  CAS  PubMed  Google Scholar 

  • Prasad, S., Semwal, P., Deshpande, S., et al. (2002). Molecular genetics of schizophrenia: Past, present and future. Journal of Biosciences, 27, 35–52.

    Article  CAS  PubMed  Google Scholar 

  • Pulver, A. E., Lasseter, V. K., Kasch, L., et al. (1995). Schizophrenia a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. American Journal of Medical Genetics, 60, 252–260.

    Article  CAS  PubMed  Google Scholar 

  • Puzyrev, V. P., & Stepanov, V. A. (1997). Pathological anatomy of human genome (p. 223). Novosibirsk: Nauka. RAS Siberian company.

    Google Scholar 

  • Rao, D., Jonsson, E. G., Paus, S., Ganguli, R., Nothen, M., & Nimgaonkar, V. L. (1998). Schizophrenia and the serotonin transporter gene [In process citation]. Psychiatric Genetics, 8, 207–212.

    Article  CAS  PubMed  Google Scholar 

  • Reich, D. E., Cargill, M., Bolk, S., et al. (2001). Linkage disequilibrium in the human genome. Nature, 411(6834), 199–204.

    Article  CAS  PubMed  Google Scholar 

  • Saito, T., Guan, F., Papolos, D. F., Rajouria, N., Fann, C. S., & Lachman, H. M. (2001). Polymorphism in SNAP29 gene promoter region associated with schizophrenia. Journal of Molecular Psychiatry, 6(2), 193–201.

    Article  CAS  Google Scholar 

  • Schwab, S. G., Eckstein, G. N., Hallmayer, J., 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. Molecular Psychiatry, 2, 156–160.

    Article  CAS  PubMed  Google Scholar 

  • Schwab, S. G., Hallmayer, J., Albus, M., Lerer, B., Eckstein, G. N., Borrmann, M., Segman, R. H., Hanses, C., Freymann, J., Yakir, A., Trixler, M., Falkai, P., Rietschel, M., Maier, W., & Wildenauer, D. B. (2000). A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: Support for loci on chromosome 10p and 6. Molecular Psychiatry, 5(6), 638–649.

    Article  CAS  PubMed  Google Scholar 

  • Shaikh, S., Collier, D., Arranz, M., Ball, D., Gill, M., & Kerwin, R. (1994). DRD2 Ser311/Cys311 polymorphism in schizophrenia. Lancet, 343(8904), 1045–1046.

    CAS  PubMed  Google Scholar 

  • Shayevitz, C., Cohen, O. S., Faraone, S. V., & Glatt, S. J. (2012). A re-review of the association between the NOTCH4 locus and schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 159(5), 477–483. doi:10.1002/ajmg.b.32050. Epub 2012 Apr 9.

    Article  CAS  Google Scholar 

  • Sherrington, R., Brynjolfsson, J., Petursson, H., Potter, M., Dudleston, K., Barraclough, B., Wasmuth, J., Dobbs, M., & Gurling, H. (1988). Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature, 336(6195), 164–167.

    Article  CAS  PubMed  Google Scholar 

  • Sidenberg, D. G., Bassett, A. S., Demchyshyn, L., et al. (1993). New polymorphism for the human serotonin 1D receptor variant (5-HT1D beta) not linked to schizophrenia in five Canadian pedigrees. Human Heredity, 43(5), 315–318.

    Article  CAS  PubMed  Google Scholar 

  • Silverman, J. M., Greenberg, D. A., Altstiel, L. D., Siever, L. J., Mohs, R. C., Smith, C. J., Zhou, G., Hollander, T. E., Yang, X. P., Kedache, M., Li, G., Zaccario, M. L., & Davis, K. L. (1996). Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree. American Journal of Medical Genetics, 67(2), 162–171.

    Article  CAS  PubMed  Google Scholar 

  • Sklar, F. H., Fitz, H. C., Wu, Y., Van Zee, R., & McVoy, C. (2001). The design of ecological landscape models for everglades restoration. Ecological Economics, 37(3), 379–401.

    Article  Google Scholar 

  • Sobell, J., Sigurdson, D. C., Heston, L., & Sommer, S. (1994). S311C D2DR variant: No association with schizophrenia. Lancet, 344(8922), 621–622.

    Article  CAS  PubMed  Google Scholar 

  • Spurlock, G., Williams, J., McGuffin, P., Aschauer, H. N., Lenzinger, E., Fuchs, K., Sieghart, W. C., Meszaros, K., Fathi, N., Laurent, C., Mallet, J., Macciardi, F., Pedrini, S., Gill, M., Hawi, Z., Gibson, S., Jazin, E. E., Yang, H. T., Adolfsson, R., Pato, C. N., Dourado, A. M., & Owen, M. J. (1998). European Multicentre Association Study of Schizophrenia: A study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms. American Journal of Medical Genetics, 81(1), 24–28.

    Article  CAS  PubMed  Google Scholar 

  • St Clair, D., Blackwood, D., Muir, W., et al. (1990). Association within a family of a balanced autosomal translocation with major mental illness. Lancet, 336, 13–16.

    Article  CAS  PubMed  Google Scholar 

  • Straub, R. E., Jiang, Y., MacLean, C. J., et al. (2002). Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse disbinding gene, is associated with schizophrenia. The American Journal of Human Genetics, 71, 337–348.

    Article  CAS  PubMed  Google Scholar 

  • Straub, R. E., MacLean, C. J., O’Neill, F. A., et al. (1997). Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families. Molecular Psychiatry, 2(N2), 148–155.

    Article  CAS  PubMed  Google Scholar 

  • Terwilliger, J. D., & Ott, J. (1994). Handbook of human genetic linkage. Baltimore, MA: JHU Press.

    Google Scholar 

  • Trubnikov, V. I., & Gindilis, V. M. (1981). Table method of the component expansion of phenotypic variance based on correlations between relatives [Article in Russian]. Genetika, 17(6), 1107–1116.

    CAS  PubMed  Google Scholar 

  • Verga, M., Macciardi, F., Pedrini, S., Cohen, S., & Smeraldi, E. (1997). No association of the Ser/Cys311 DRD2 molecular variant with schizophrenia using a classical case control study and the haplotype relative risk. Schizophrenia Research, 25(2), 117–121.

    Article  CAS  PubMed  Google Scholar 

  • Wang, Z. W., Black, D., Andreasen, N. C., & Crowe, R. R. (1993). A linkage study of chromosome 11q in schizophrenia. Archives of General Psychiatry, 50(3), 212–216.

    Article  CAS  PubMed  Google Scholar 

  • Waterwort, D. M., Bassett, A. S., & Brzustowicz, L. M. (2002). Recent advances in the genetics of schizophrenia. Cellular and Molecular Life Sciences, 59(2), 331–348.

    Article  CAS  PubMed  Google Scholar 

  • Wei, J., & Hemmimgs, G. P. (2000). The NOTCH4 locus is associated with susceptibility to schizophrenia. Nature Genetics, 25(4), 376–377.

    Article  CAS  PubMed  Google Scholar 

  • Williams, J., Spurlock, G., McGuffin, P., Mallet, J., Nöthen, M. M., Gill, M., Aschauer, H., Nylander, P. O., Macciardi, F., & Owen, M. J. (1996). Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group. Lancet, 347(9011), 1294–1296.

    Article  CAS  PubMed  Google Scholar 

  • Zavattari, P., Lampis, R., & Mulargia, A. (2000). Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia. Human Molecular Genetics, 9(20), 2967–2972.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. N.I.Vavilov Inst. of General Genet, Russian Academy of Sciences, Moscow, Russia

    Kazima Bulayeva

  2. N.I.Vavilov Inst. of General Geneti, Russian Academy of Sciences, Moscow, Russia

    Oleg Bulayev

  3. Dept. Psychiatry and Behavioral Sci, SUNY Upstate Medical University, Syracuse, New York, USA

    Stephen Glatt

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Bulayeva, K., Bulayev, O., Glatt, S. (2016). Current Problems of Complex Disease Genes Mapping. In: Genomic Architecture of Schizophrenia Across Diverse Genetic Isolates. Springer, Cham. https://doi.org/10.1007/978-3-319-31964-3_1

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