Hostname: page-component-848d4c4894-nr4z6 Total loading time: 0 Render date: 2024-05-17T14:12:37.727Z Has data issue: false hasContentIssue false
  • English
  • Français

Major Psychosis and Chromosome 22: Genetics Meets Epigenetics

Published online by Cambridge University Press:  07 November 2014

Arturas Petronis ,
Violeta Popendikyte ,
Peixiang Kan  and
Tsukasa Sasaki
Get access Rights & Permissions [Opens in a new window]

Abstract

Elucidation of genetic factors in schizophrenia and bipolar disorder remains a challenging task to psychiatric researchers. As a rule, data from genetic linkage and association studies are quite controversial. In this article, we further explore the possibility that in addition to DNA sequence variation, a putative epigenetic dysregulation of brain genes plays an important role in the etiopathogenesis of major psychosis. We provide an epigenetic interpretation of unclear genetic findings specifically pertaining to chromosome 22 in schizophrenia and bipolar disorder. It is suggested that epigenetic strategies, when applied in conjunction with traditional genetic ones, may significantly expedite the uncovering of the molecular causes of major psychosis.

Type
Feature Article
Information
CNS Spectrums , Volume 7 , Issue 3 , March 2002 , pp. 209 - 214
Copyright
Copyright © Cambridge University Press 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Reiss, D, Plomin, R, Hetherington, EM. Genetics and psychiatry: an unheralded window on the environment. Am J Psychiatry. 1991;148:283–291.Google ScholarPubMed
2.Henikoff, S, Matzke, MA. Exploring and explaining epigenetic effects. Trends Genet 1997;13:293–295.CrossRefGoogle ScholarPubMed
3.Monk, M. Variation in epigenetic inheritance. Trends Genet 1990;6:110–114.CrossRefGoogle ScholarPubMed
4.Holliday, R. DNA methylation in eukaryotes: 20 years on. In: Russo, V, Martienssen, R, Riggs, A, eds. Epigenetic Mechanisms of Gene Regulation. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1996:5–27.Google Scholar
5.Wigler, M, Levy, D, Perucho, M. The somatic replication of DNA methylation. Cell. 1981;24:33–40.CrossRefGoogle ScholarPubMed
6.Petronis, A. Human morbid genetics revisited: relevance of epigenetics. Trends Genet. 2001;17:142–146.CrossRefGoogle ScholarPubMed
7.Petronis, A, Paterson, AD, Kennedy, JL. Schizophrenia: an epigenetic puzzle? Schizophr Bull. 1999;25:639–655.CrossRefGoogle ScholarPubMed
8.Petronis, A. The genes for major psychosis: aberrant sequence or regulation? Neuropsychopharmacology. 2000;23:1–12.CrossRefGoogle ScholarPubMed
9.Schwab, SG, Wildenauer, DB. Chromosome 22 workshop report. Am J Med Genet. 1999;88:276–278.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
10.Yamamoto, K, Bloom, D, La, S, et al.Polymorphism in the cell division cycle 45 like gene and schizophrenia. Am J Med Genet. 2001;105:214–215.CrossRefGoogle ScholarPubMed
11.Saito, T, Guan, F, Papolos, DF, Rajouria, N, Fann, CS, Lachman, HM. Polymorphism in SNAP29 gene promoter region associated with schizophrenia. Mol Psychiatry. 2001;6:193–201.CrossRefGoogle ScholarPubMed
12.Hung, CC, Chen, YH, Tsai, MT, Chen, CH. Systematic search for mutations in the human tissue inhibitor of metalloproteinases-3 (TIMP-3) gene on chromosome 22 and association study with schizophrenia. Am J Med Genet. 2001;105:275–278.CrossRefGoogle ScholarPubMed
13.Parsian, A, Suarez, BK, Isenberg, K, et al.No evidence for a schizophrenia susceptibility gene in the vicinity of IL2RB on chromosome 22. Am J Med Genet. 1997;74:361–364.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
14.Deckert, J, Nothen, MM, Rietschel, M, et al.Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia. J Neural Transm. 1996;103:1447–1455.CrossRefGoogle ScholarPubMed
15.Hayakawa, T, Ishiguro, H, Toru, M, Hamaguchi, H, Arinami, T. Systematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in schizophrenics. Psychiatr Genet. 1998;8:33–36.CrossRefGoogle ScholarPubMed
16.Toyooka, K, Muratake, T, Tanaka, T, et al.14-3-3 protein eta chain gene (YWHAH) polymorphism and its genetic association with schizophrenia. Am J Med Genet. 1999;88:164–167.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
17.Saito, T, Papolos, DF, Chernak, D, Rapaport, MH, Kelsoe, JR, Lachman, HM. Analysis of GNAZ gene polymorphism in bipolar affective disorder. Am J Med Genet. 1999;88:324–328.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
18.Ohtsuki, T, Ichiki, R, Toru, M, Arinami, T. Mutational analysis of the synapsin III gene on chromosome 22q12-q13 in schizophrenia. Psychiatry Res. 2000;94:1–7.CrossRefGoogle ScholarPubMed
19.Stober, G, Meyer, J, Nanda, I, et al.Linkage and family-based association study of schizophrenia and the synapsin III locus that maps to chromosome 22q13. Am J Med Genet. 2000;96:392–397.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
20.Palmatier, MA, Kang, AM, Kidd, KK. Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biol Psychiatry. 1999;46:557–567.CrossRefGoogle ScholarPubMed
21.Li, T, Sham, PC, Vallada, H, et al.Preferential transmission of the high activity allele of COMT in schizophrenia. Psychiatr Genet. 1996;6:131–133.CrossRefGoogle ScholarPubMed
22.Egan, MF, Goldberg, TE, Kolachana, BS, et al.Effect of COMT Va1108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001;98:6917–6922.CrossRefGoogle ScholarPubMed
23.Ohmori, O, Shinkai, T, Kojima, H, et al.Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics. Neurosci Lett. 1998;243:109–112.CrossRefGoogle ScholarPubMed
24.Herken, H, Erdal, ME. Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and prognosis. Psychiatr Genet. 2001;11:105–109.CrossRefGoogle ScholarPubMed
25.Nolan, KA, Volavka, J, Czobor, P, et al.Suicidal behavior in patients with schizophrenia is related to COMT polymorphism. Psychiatr Genet. 2000;10:117–124.CrossRefGoogle ScholarPubMed
26.Kotler, M, Barak, P, Cohen, H, et al.Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol-O-methyltransferase (COMT) activity. Am J Med Genet. 1999;88:628–633.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
27.Karayiorgou, M, Altemus, M, Galke, BL, et al.Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci U S A. 1997;94:4572–4575.CrossRefGoogle ScholarPubMed
28.Karayiorgou, M, Sobin, C, Blundell, ML, et al.Family-based association studies support a sexually dimorphic effect of COMT and MAOA on genetic susceptibility to obsessive-compulsive disorder. Biol Psychiatry. 1999;45:1178–1189.CrossRefGoogle ScholarPubMed
29.Schindler, KM, Richter, MA, Kennedy, JL, Pato, MT, Pato, CN. Association between homozygosity at the COMT gene locus and obsessive compulsive disorder. Am J Med Genet. 2000;96:721–724.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
30.Petronis, A, Kennedy, JL. Unstable genes-unstable mind? Am J Psychiatry. 1995;152:164–172.Google ScholarPubMed
31.Margolis, RL, McInnis, MG, Rosenblatt, A, Ross, CA. Trinucleotide repeat expansion and neuropsychiatric disease. Arch Gen Psychiatry. 1999;56:1019–1031.CrossRefGoogle ScholarPubMed
32.Saleem, Q, Dash, D, Gandhi, C, et al.Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder. Mol Psychiatry. 2001;6:694–700.CrossRefGoogle ScholarPubMed
33.Karayiorgou, M, Morris, MA, Morrow, B, et al.Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proc Natl Acad Sci U S A. 1995;92:7612–7616.CrossRefGoogle ScholarPubMed
34.Arnold, PD, Siegel-Bartelt, J, Cytrynbaum, C, Teshima, I, Schachar, R. Velo-cardio-facial syndrome: implications of microdeletion 22q11 for schizophrenia and mood disorders. Am J Med Genet. 2001;105:354–362.CrossRefGoogle ScholarPubMed
35.Papolos, DF, Faedda, GL, Veit, S, et al.Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? Am J Psychiatry. 1996;153:1541–1547.Google ScholarPubMed
36.Bassett, AS, Chow, EW. 22q11 deletion syndrome: a genetic subtype of schizophrenia. Biol Psychiatry. 1999;46:882–891.CrossRefGoogle ScholarPubMed
37.Gothelf, D, Frisch, A, Munitz, H, et al.Velocardiofacial manifestations and microdeletions in schizophrenic inpatients. Am J Med Genet. 1997;72:455–461.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
38.Eliez, S, Blasey, CM, Schmitt, EJ, White, CD, Hu, D, Reiss, AL. Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia? Am J Psychiatry. 2001;158:447–453.CrossRefGoogle ScholarPubMed
39.Chow, EW, Mikulis, DJ, Zipursky, RB, Scutt, LE, Weksberg, R, Bassett, AS. Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia. Biol Psychiatry. 1999;46:1436–1442.CrossRefGoogle ScholarPubMed
40.Chow, EW, Bassett, AS, Weksberg, R. Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics. Am J Med Genet. 1994;54:107–112.CrossRefGoogle ScholarPubMed
41.Usiskin, SI, Nicolson, R, Krasnewich, DM, et al.Velocardiofacial syndrome in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry. 1999;38:1536–1543.CrossRefGoogle ScholarPubMed
42.Carlson, C, Papolos, D, Pandita, RK, et al.Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders. Am J Hum Genet. 1997;60:851–859.Google ScholarPubMed
43.Klar, AJ. Propagating epigenetic states through meiosis: where Mendel's gene is more than a DNA moiety. Trends Genet. 1998;14:299–301.CrossRefGoogle ScholarPubMed
44.Cavalli, G, Paro, R. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell. 1998;93:505–518.CrossRefGoogle ScholarPubMed
45.Allen, ND, Norris, ML, Surani, MA. Epigenetic control of transgene expression and imprinting by genotype-specific modifiers. Cell. 1990;61:853–861.CrossRefGoogle ScholarPubMed
46.Silva, A, White, R. Inheritance of allelic blueprints for methylation patterns. Cell. 1988;54:145–152.CrossRefGoogle ScholarPubMed
47.Morgan, HD, Sutherland, HG, Martin, DI, Whitelaw, E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23:314–318.CrossRefGoogle ScholarPubMed
48.Jablonka, E, Lamb, M. Epigenetic Inheritance and Evolution. Oxford, England: Oxford University Press; 1995.CrossRefGoogle Scholar
49.Vallada, H, Collier, D. Genetics of schizophrenia—new findings. In: Gattaz, WF, Hafner, H, eds. Search for the Causes of Schizophrenia. Berlin/New York: Springer-Verlag; 1998:1–9.Google Scholar
50.Kelsoe, JR, Spence, MA, Loetscher, E, et al.A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22. Proc Natl Acad Sci U S A. 2001;98:585–590.CrossRefGoogle ScholarPubMed
51.Dib, C, Faure, S, Fizames, C, et al.A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996;380:152–154.CrossRefGoogle Scholar
52.DeLisi, L, Shaw, S, Crow, T. A genome-wide scan in 301 families with sibling-pairs diagnosed with schizophrenia of schizoaffective disorder suggests linkage to chromosomes 2pcen and 10p14. Am J Med Genet. 2001;105:561–578.Google Scholar
53.Eliez, S, Antonarakis, SE, Morris, MA, Dahoun, SP, Reiss, AL. Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study. Arch Gen Psychiatry. 2001;58:64–68.CrossRefGoogle ScholarPubMed
54.Wolffe, AP, Matzke, MA. Epigenetics: regulation through repression. Science. 1999;286:481–486.CrossRefGoogle ScholarPubMed
55.Nicholls, RD. The impact of genomic imprinting for neurobehavioral and developmental disorders. J Clin Invest. 2000;105:413–418.CrossRefGoogle ScholarPubMed
56.Ferguson-Smith, AC, Surani, MA. Imprinting and the epigenetic asymmetry between parental genomes. Science. 2001;293:1086–1089.CrossRefGoogle ScholarPubMed
57.Paulsen, M, El-Maarri, O, Engemann, S, et al.Sequence conservation and variability of imprinting in the beckwith-wiedemann syndrome gene cluster in human and mouse. Hum Mol Genet. 2000;9:1829–1841.CrossRefGoogle ScholarPubMed
58.Popendikyte, V, Laurinavicius, A, Paterson, AD, Macciardi, F, Kennedy, JL, Petronis, A. DNA methylation at the putative promoter region of the human dopamine D2 receptor gene. Neuroreport. 1999;10:1249–1255.CrossRefGoogle ScholarPubMed
59.De Luca, A, Pasini, A, Amati, F, et al.Association study of a promoter polymorphism of UFD1L gene with schizophrenia. Am J Med Genet. 2001;105:529–533.CrossRefGoogle ScholarPubMed
60.Wong, A, Macciardi, F, Buckle, C, et al. Possible association between schizophrenia and the 14-3-3 eta gene [abstract]. Annual Meeting of the Society of Neuroscience; 2001; San Diego, CA. Abstract 571.11.Google Scholar
61.Vawter, MP, Barrett, T, Cheadle, C, et al.Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res Bull. 2001;55:641–650.CrossRefGoogle ScholarPubMed
62.Hagerman, R. Clinical and diagnostic aspects of fragile X syndrome. In: Wells, R, Warren, S, eds. Genetic Instabilities and Hereditary Neurological Diseases. San Diego, CA: Academic Press; 1998:15–25.Google Scholar
63.Steinbach, P, Glaser, D, Vogel, W, Wolf, M, Schwemmle, S. The DMPK gene of severely affected myotonic dystrophy patients is hypermethylated proximal to the largely expanded CTG repeat. Am J Hum Genet. 1998;62:278–285.CrossRefGoogle Scholar
64.Filippova, GN, Thienes, CP, Penn, BH, et al.CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet. 2001;28:335–343.CrossRefGoogle Scholar
65.Petronis, A, Vincent, JB, Surh, LC, Ashizawa, T, Kennedy, JL. Polyglutamine-containing proteins in schizophrenia: an effect of lymphoblastoid cells? Mol Psychiatry. 2000;5:234–236.CrossRefGoogle ScholarPubMed
66.Kugoh, H, Mitsuya, K, Meguro, M, Shigenami, K, Schulz, TC, Oshimura, M. Mouse A9 cells containing single human chromosomes for analysis of genomic imprinting. DNA Res. 1999;6:165–172.CrossRefGoogle ScholarPubMed
67.Meguro, M, Mitsuya, K, Sui, H, et al.Evidence for uniparental, paternal expression of the human GABAA receptor subunit genes, using microcell-mediated chromosome transfer. Hum Mol Genet. 1997;6:2127–2133.CrossRefGoogle ScholarPubMed
68.Gabriel, JM, Higgins, MJ, Gebuhr, TC, Shows, TB, Saitoh, S, Nicholls, RD. A model system to study genomic imprinting of human genes. Proc Natl Acad Sci U S A. 1998;95:14857–14862.CrossRefGoogle Scholar
69.Emmert-Buck, MR, Bonner, RF, Smith, PD, et al.Laser capture microdissection. Science. 1996;274:998–1001.CrossRefGoogle ScholarPubMed
70.Frommer, M, McDonald, LE, Millar, DS, et al.A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A. 1992;89:1827–1831.CrossRefGoogle ScholarPubMed
71. Affymetrix company web site [list]. Available at: http://www.affymetrix.com. Accessed December, 15 2001.Google Scholar
72.Gitan, R, Shi, H, Yan, P, Huang, T. Methylation-specific oligonucleotide microarray: a new potential for high throughput methylation analysis. Genome Res. In press.Google Scholar