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From genomics to proteomics: new directions in molecular neuropsychiatry

Published online by Cambridge University Press:  24 June 2014

Amy F. Eisener ,
Carlos N. Pato ,
Mantosh Dewan  and
Michele T. Pato
Amy F. Eisener
Affiliation:
Center for Psychiatric and Molecular Genetics, Department of Psychiatry, SUNY Upstate Medical University, Syracuse
Carlos N. Pato
Affiliation:
Center for Psychiatric and Molecular Genetics, Department of Psychiatry, SUNY Upstate Medical University, Syracuse Veterans Administration, Medical center Syracuse Center for Neuroscience, Universidade de Coimbra, Portugal
Mantosh Dewan
Affiliation:
Center for Psychiatric and Molecular Genetics, Department of Psychiatry, SUNY Upstate Medical University, Syracuse
Michele T. Pato*
Affiliation:
Center for Psychiatric and Molecular Genetics, Department of Psychiatry, SUNY Upstate Medical University, Syracuse Veterans Administration, Medical center Syracuse Center for Neuroscience, Universidade de Coimbra, Portugal
*
Michele T. Pato MD, Center for Psychiatric and Molecular Genetics, Department of Psychiatry, SUNY Upstate Medical University, 750 East Adams St, Syracuse, NY 13210, USA. Tel: (315) 464-3206; Fax: (315) 464-3255; E-mail: [email protected]
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Abstract

Neuropsychiatry, like many other biomedical sciences, has been revolutionized by the advances in genomic technologies over the years. The advent of PCR (polymerase chain reaction) and the sequencing of the human genome have provided invaluable insights into the molecular genetics of the various psychiatric disorders through the study of candidate genes and linkage analyses. However, biological phenotype is dictated by protein expression, which has been shown to stray from the genetic blueprint designated by the genome. Consequently, the field of proteomics has recently emerged as a powerful means of exploring protein structure, function, and expression patterns. The ability to study disease at the gene and protein levels presents a tremendous opportunity for neuropsychiatric research, particularly in terms of the potential for developing therapeutic agents for novel protein targets.

Keywords

drug discoverygenomicsmolecular geneticspostgenomicsprotein analysisproteomics
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 15 , Issue 6 , December 2003 , pp. 388 - 397
Copyright
Copyright © 2003 Blackwell Munksgaard

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References

Gottesman, II, Shields, J.Schizophrenia, the epigenetic puzzle. Cambridge: Cambridge University Press, 1982. Google Scholar
Pato, CN, Lander, ES, Schultz, SC.Prospects for the genetic analysis of schizophrenia. Schizophr Bull 1989;15: 365–372.CrossRefGoogle ScholarPubMed
Tsuang, MT, Faraone, SV. The genetics of mood disorders. Baltimore: Johns Hopkins University Press, 1990. Google Scholar
Faraone, SV, Kremen, WS, Tsuang, MT.Genetic transmission of major affective disorders: quantitative models and linkage analyses. Psychol Bull 1990;108: 109–127.CrossRefGoogle ScholarPubMed
Kennedy, JL, Pato, MT, Bauer, A, Carvalho, C, Pato, CN.Genetics of schizophrenia current findings and issues. CNS Spectrums 1999;4: 17–21. CrossRefGoogle Scholar
Pato, CN, Azevedo, MH, Pato, MTet al. Selection of homogeneous populations for genetic study. The Portuguese Genetics of Psychosis Project. Am J Med General (Neuropsychiatric Genet) 1997;74: 286–288. 3.0.CO;2-O>CrossRefGoogle Scholar
Schindler, KM, Dalla Torre, C, Bauer, Aet al. Identification of a highly homogeneous population for genetic study of psychiatric disorders. CNS Spectrums 1999;4: 22–24. CrossRefGoogle Scholar
Falk, CT, Rubinstein, P.Haplotype relative-risk: an easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet 1987;51: 227–233.CrossRefGoogle ScholarPubMed
Risch, NJ.Searching for genetic determinants in the new millennium. Nature 2000;405: 847–856.CrossRefGoogle ScholarPubMed
Spielman, RS, McGinnis, R, Ewens, WJ.Transmission test for linkage disequilibrium. the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993;56: 777–787. Google Scholar
Spielman, RS, Ewens, WJ.The TDT and other family-based test for linkage disequilibrium and association. Am J Hum Genet 1996;59: 983–989.Google Scholar
Rabinowitz, D, Laird, NM.A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered 2000;50: 211–223.CrossRefGoogle ScholarPubMed
Lake, SL, Blacker, D, Laird, NM.Family–based tests of association in the presence of linkage. Am J Hum Genet 2000;67: 1515–1525.CrossRefGoogle ScholarPubMed
Arinami, T, Gao, M, Hamaguchi, H, Toru, M.A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum Mol Genet 1997;6: 577–582.CrossRefGoogle ScholarPubMed
Jonsson, EG, Nothen, MM, Neidt, Het al. Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia. Schizophr Res 1999;40: 31–36.CrossRefGoogle Scholar
Ohara, K, Hagai, M, Tami, K, Nakamura, Y, Ino, A, Ohara, K.Functional polymorphism of −141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia. Psychiatr Res 1998;81: 117–123. CrossRefGoogle Scholar
Breen, G, Brown, J, Maude, S, Et Al., –141C del/ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population. Am J Med Genet 1999;88: 407–410.3.0.CO;2-3>CrossRefGoogle Scholar
Li, T, Arranz, M, Aitchison, KJet al. Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia. Schizophr Res 1998;32: 87–92.Google Scholar
Tallerico, T, Ulpian, C, Liu, IS.Dopamine D2 receptor promoter polymorphism: no association with schizophrenia. Psychiatr Res 1999;85: 215–219. CrossRefGoogle ScholarPubMed
Stober, G, Jatzke, AH, Jungkunz, Get al. Insertion/deletion variant (−141 C Ins/Del) in the 5′regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. J Neural Transm 1998;105: 101–109.Google Scholar
Arranz, MJ, Munro, J, Li, T, Collier, DA, Kirov, G, Kerwin, RW.A polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and drug response: association studies. Schizophr Res 1998; 29: 127. Google Scholar
Schindler, KM, Pato, MT, Dourado, Aet al. Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population. Molecular Psychiatry, 2002;7: 1002–1005.CrossRefGoogle Scholar
Freedman, R, Coon, H, Myles-Worsley, Met al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997;94: 587–592.CrossRefGoogle ScholarPubMed
Faraone, SV, Matise, T, Svrakic, Det al. Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium. Am J Med Genet 1998;81: 290–295.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
Xu, J, Pato, MT, Dalla Torre, Cet al. Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. Am J Med Genet 2001;105: 669–674.CrossRefGoogle ScholarPubMed
Pulver, AE, Karayiorgou, M, Lasseter, VKet al. Follow-up of a report of a potential linkage for schizophrenia on chromosome 22q12-q13. 1: Part 2. Am J Medical Genet 1994;54: 44–50. CrossRefGoogle ScholarPubMed
Wong, AHC, Macciardi, F, Klepman, Tet al. Identification of candidate genes for psychosis in rat models and possible association between schizophrenia and the 14–3−3_ gene. Molecular Psychiatry, 2003;8: 156–166. CrossRefGoogle Scholar
Badner, JA, Gershon, ES.Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002;7: 405–411.CrossRefGoogle Scholar
Pato, CN, Macedo, A, Ambrosio, Aet al. Detection of expansion regions in Portuguese bipolar families. Am J Med Genet 2000;96: 854–857.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Vincent, JB, Yuan, QP, Schalling, Met al. Long repeat tracts at SCA8 in major psychosis. Am J Med Genet 2000;96: 873–876.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Blouin, JL, Dombroski, BA, Nath, SKet al. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21. Nat Genet 1998;20: 70–73.Google ScholarPubMed
Brzustowicz, LM, Hodgkinson, KA, Chow, EWC, Honer, WG, Bassett, A.Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21-q22. Science 2000;288: 678–682.CrossRefGoogle Scholar
Cao, Q, Martinez, M, Zhang, Jet al. Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 1997;43: 1–8.CrossRefGoogle Scholar
Diehl, SR, Wang, S, Detera-Wadleigh, Set al. Evidence suggesting possible SCA1 gene involvement in schizophrenia. Am J Hum Genet 1994;55S: 867. Google Scholar
Dann, J, Delisi, LE, Devoto, Met al. A linkage study of schizophrenia to markers within Xp11 near the MAOB gene. Psychiatr Res 1997;70: 131–143. CrossRefGoogle ScholarPubMed
Gill, M, Vallada, H, Collier, Det al. A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22). Am J Med Genet 1996;67: 40–45.3.0.CO;2-W>CrossRefGoogle Scholar
Kaufmann, CA, Suarez, B, Malaspina, Det al. Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees. Am J Med Genet 1998;81: 282–289.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Kendler, KS, MacLean, CJ, O'Neill, FAet al. Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families. Am J Psychiatry 1996;153: 1534–1540.Google ScholarPubMed
Levinson, DF, Mahtani, MM, Nancarrow, DJet al. Genome scan of schizophrenia. Am J Psychiatry 1998;155: 741–750.Google ScholarPubMed
Lin, MW, Sham, P, Hwu, HG, Collier, D, Murray, R, Powell, JF.Suggestive evidence for linkage of schizophrenia to markers on chromosome 13 in Caucasian but not Oriental populations. Hum Genet 1997;99: 417–420.CrossRefGoogle Scholar
Lindholm, E, Ekholm, B, Balciuniene, Jet al. Linkage analysis of a large Swedish kindred provides further support for a susceptibility locus for schizophrenia on chromosome 6p23. Am J Med Genet 1999;88: 369–377.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Martinez, M, Goldin, LR, Cao, Qet al. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J Med Genet 1999;88: 337–343.3.0.CO;2-A>CrossRefGoogle ScholarPubMed
Maziade, M, Raymond, V, Cliché, Det al. Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia. Am J Med Genet 1995;60: 522–528.CrossRefGoogle ScholarPubMed
Moises, HW, Yang, L, Kristbjarnarson, Het al. An international two-stage genome-wide search for schizophrenia susceptibility genes. Nat Genet 1995;11: 321–324.CrossRefGoogle ScholarPubMed
Pulver, AE, Lasseter, VK, Kasch, Let al. Schizophrenia: a genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes. Am J Med Genet 1995;60: 252–260.CrossRefGoogle ScholarPubMed
Schwab, SG, Eckstein, GN, Hallmayer, Jet al. 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 1997;2: 156–160.CrossRefGoogle ScholarPubMed
Schwab, SG, Hallmayer, J, Albus, Met al. Further evidence for a susceptibility locus on chromosome 10p14–11 in 72 families with schizophrenia by nonparametric linkage analysis. Am J Med Genet 1998;81: 302–307.3.0.CO;2-V>CrossRefGoogle Scholar
Schizophrenia Linkage Collaborative Groupfor Chromosomes 3, 6, and 8. Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study. Am J Medical Genet 1996;67: 580–594. 3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Straub, RE, MacLean, CJ, O'Neill, FAet al. A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity. Nature Genet 1995;11: 287–293.CrossRefGoogle ScholarPubMed
Straub, RE, MacLean, CJ, O'Neill, FA, Walsh, D, Kendler, KS.Support for a possible schizophrenia vulnerability locus in region 5q22–31 in Irish families. Mol Psychiatry 1997;2: 148–155.CrossRefGoogle ScholarPubMed
Straub, RE, MacLean, CJ, Martin, RBet al. A schizophrenia locus may be located in region 10p15-p11. Am J Med Genet 1998;81: 296–301.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Wildenauer, DB, Schwab, SG, Hallmayer, Jet al. Genome scan for autosomal genes conferring risk to schizophrenia in a German/Israeli sample [Abstract]. Am J Med Genet 1998;51: 454. Google Scholar
Williams, NM, Rees, ML, Holmans, Pet al. A two-stage genome scan for schizophrenia susceptibility genes in 196 affected subbing pairs. Hum Mol Genet 1999;8: 1729–1739.CrossRefGoogle Scholar
Edgar, PF, Douglas, JE, Cooper, GJS, Dean, B, Kydd, R, Faull, RL M.Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia. Mol Psychiatry 2000;5: 85–90.CrossRefGoogle Scholar
Johnston-Wilson, NL, Sims, CD, Hofmann, J-Pet al. Disease-specific alteration in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Mol Psychiatry 2000;5: 142–149.CrossRefGoogle Scholar
Manji, HK, Zarate, CA.Molecular and cellular mechanisms underlying mood stabilization in bipolar disorder. implications for the development of improved therapeutics. Mol Psychiatry 2002;7: S1–S7.CrossRefGoogle ScholarPubMed
Gygi, SP, Rochon, Y, Franza, BR, Aebersold, R.Correlation between Protein and mRNA Abundance in Yeast. Mol Cell Biol 1999;19: 1720–1730.CrossRefGoogle Scholar
Blackstock, WP, Weir, MP.Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 1999;17: 121–127.CrossRefGoogle ScholarPubMed
Oliver, SG, Van Der Aart, QJ, Agostoni-Carbone, MLet al. The complete DNA sequence of yeast chromosome III. Nature 1992;357: 38–46.CrossRefGoogle ScholarPubMed
Wasinger, VC, Cordwell, SJ, Cerpa-Poljak, Aet al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis 1995;16: 1090–1094.CrossRefGoogle ScholarPubMed
Pandey, A, Mann, M.Proteomics to study genes and genomes. Nature 2000;405: 837–846.Google ScholarPubMed
Reynolds, T.For proteomics research, a new race has begun. J Natl Cancer Inst 2002;94: 552–554.CrossRefGoogle ScholarPubMed
Ng, JH, Ilag, LL.Functional proteomics: separating the substance from the hype. Drug Discovery Today 2002;7: 504–505.CrossRefGoogle ScholarPubMed
Dongre, AR, Opiteck, G, Cosand, WL, Hefta, SA.Proteomics in the post-genome age. Biopolymers 2001;60: 206–211.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Graves, PR & Haystead, TA J.Molecular biologist's guide to proteomics. Microbiol Mol Biol Rev 2002;66: 39–63.CrossRefGoogle ScholarPubMed
Corbett, JM, Dunn, MJ, Posch, A, Gorg, A.Positional reproducibility of protein spots in two-dimensional polyacrylamide electrophoresis using immobilized pH gradient isoelectric focusing in the first dimension – an interlaboratory comparison. Electrophoresis 1994;15: 1205–1211.CrossRefGoogle Scholar
Righetti, PG & Drysdale, JW.Small-scale fractionation of proteins and nucleic acids by isoelectric focusing in polyacrylamide gels. Ann NY Acad Sci 1973;209: 163–186.CrossRefGoogle ScholarPubMed
Witzmann, FA & Li, J.Cutting-edge technology. II. Proteomics: core technologies and applications in physiology. Am J Gastrointestinal Liver Physiol 2002;282: G735–G741. CrossRefGoogle ScholarPubMed
Wilkins, MR, Sanchez, JC, Gooley, AAet al. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol General Eng Rev 1995;13: 19–50. CrossRefGoogle ScholarPubMed
Celis, JE, Olsen, E.A qualitative and quantitative protein database approach identifies individual and groups of functionally related proteins that are differentially regulated in simian virus 40 (SV40) transformed human keratinocytes: an overview of the functional changes associated with the transformed phenotype. Electrophoresis 1994;15: 309–344.CrossRefGoogle ScholarPubMed
Panisko, EA, Conrads, TP, Goshe, MB, Veenstra, TD.The postgenomic age: characterization of proteomes. Exp Hematol 2002;30: 97–107.CrossRefGoogle ScholarPubMed
Pasinetti, GM, Ho, L.From cDNA microarrays to high-throughput proteomics. Implications in the search for preventative initiatives to slow the clinical progression of Alzheimer's disease dementia. Rest Neurol Neurosci 2001;18: 137–142. Google Scholar
Fung, ET, Wright, GL Jr, , Dalmasso, EA.Proteomic strategies for biomarker identification: progress and challenges. Curr Opin Mol Ther 2000;2: 643–650.Google ScholarPubMed
Schweitzer, B, Kingsmore, SF.Measuring proteins on microarrays. Curr Opin Biotechnol 2002;13: 14–19.CrossRefGoogle ScholarPubMed
Henzel, WJ, Billeci, TM, Stults, JT, Wong, SC.Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc Natl Acad Sci USA 1993;90: 5011–5015.CrossRefGoogle ScholarPubMed
Liebler, DC.Proteomic approaches to characterize protein modifications. new tools to study the effects of environmental exposures. Environ Health Persp 2002;110(Suppl. 1):3–9. CrossRefGoogle ScholarPubMed
Jeffery, CJ, Moonlighting proteins. Trends in Biochemical Sciences, ;24 (1) 1999, 8–11.CrossRefGoogle ScholarPubMed
Yanagida, M.Functional proteomics;current achievements. J Chromatogr B 2002;771: 89–106. CrossRefGoogle ScholarPubMed
Rigaut, G, Shevchenko, A, Rutz, B, Wilm, M, Mann, M, Seraphin, B.A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 1999;17: 1030–1032.CrossRefGoogle ScholarPubMed
Jay, DG.Selective destruction of protein function by chromophore-assisted laser inactivation. Proc Natl Acad Sci USA 1988;85: 5454–5458.CrossRefGoogle ScholarPubMed
Rubenwolf, S, Niewohner, J, Meyer, Eet al. Functional proteomics using chromophore-assisted laser inactivation. Proteomics 2002;2: 241–246.3.0.CO;2-7>CrossRefGoogle ScholarPubMed