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Finding Genes for Bipolar Disorder in the Functional Genomics Era: From Convergent Functional Genomics to Phenomics and Back

Published online by Cambridge University Press:  07 November 2014

Abstract

Psychiatric genetics, while promising to unravel the mechanisms of psychiatric disorders, has proven to be a challenging field. Psychiatric disorders, like other common genetic traits, are complex and heterogeneous. Psychiatric genetics has also suffered from a lack of quantifiable, biology-based phenotypes. However, the field is currently at an opportune moment. The work of various investigators is on the verge of paying rich dividends. Efforts at positional cloning are being greatly accelerated by the fruits of the Human Genome Project. New tools of functional genomics, such as expression profiling and proteomics, are being applied to animal models. These two methods can complement each other in an approach we have termed convergent functional genomics. Lastly, improvements in the measurement of biologically distinct endophenotypes—or phenomics—will lead to a better understanding of the mapping of genes to phenotypes in both animal and human systems.

Type
Feature Article
Copyright
Copyright © Cambridge University Press 2002

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References

REFERENCES

1.Tsuang, MT, Faraone, SV. The Genetics of Mood Disorders. Baltimore, Md: Johns Hopkins University Press; 1990.Google Scholar
2.Prathikanti, S, McMahon, FJ. Genome scans for susceptibility genes in bipolar affective disorder. Ann Med. 2001;33:257262.CrossRefGoogle ScholarPubMed
3.Craddock, N, Jones, I. Molecular genetics of bipolar disorder. Br J Psychiatry. 2001;178(suppl):128133.CrossRefGoogle ScholarPubMed
4.Kelsoe, JR. Recent progress in the search for genes for bipolar disorder. Current Psychiatry Reports. 1999;1:135140.CrossRefGoogle ScholarPubMed
5.Berrettini, WH. Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia. Biol Psychiatry. 2000;47:245251.CrossRefGoogle ScholarPubMed
6.Terwilliger, JD, Shannon, WD, Lathrop, GM, et al.True and false positive peaks in genomewide scans: applications of length-biased sampling to linkage mapping. Am J Hum Genet. 1997;61:430438.CrossRefGoogle ScholarPubMed
7.Venter, JC, Adams, MD, Myers, EW, et al.The sequence of the human genome. Science. 2001;291:13041351.CrossRefGoogle ScholarPubMed
8.Lander, ES, Linton, LM, Birren, B, et al.Initial sequencing and analysis of the human genome. Nature. 2001;409:860921.Google ScholarPubMed
9.Sibille, E, Hen, R. Combining genetic and genomic approaches to study mood disorders. Eur Neuropsychopharmacol. 2001;11:413421.CrossRefGoogle ScholarPubMed
10.Rossant, J, McKerlie, C. Mouse-based phenogenomics for modeling human disease. Trends Mol Med. 2001;7:502507.CrossRefGoogle Scholar
11.Gainetdinov, RR, Jones, SR, Caron, MG. Functional hyperdopaminergia in dopamine transporter knock-out mice. Biol Psychiatry. 1999;46:303311.CrossRefGoogle ScholarPubMed
12.Ralph, RJ, Paulus, MP, Furmagalli, F, Caron, MG, Geyer, MA. Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock-out mice: differential effects of D1 and D2 receptor antagonists. J Neurosci. 2001;21:305313.CrossRefGoogle ScholarPubMed
13.Decker, S, Grider, G, Cobb, M, et al.Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness. Prog Neuropsychopharmacol Biol Psychiatry. 2000;24:455462.CrossRefGoogle ScholarPubMed
14.Petty, F, Sherman, AD. A pharmacologically pertinent animal model of mania. J Affect Disord. 1981;3:381387.CrossRefGoogle ScholarPubMed
15.Fibiger, HC. The dopamine hypothesis of schizophrenia and mood disorders: contradictions and speculations. In: The Mesolimbic Dopamine System: from Motivation to Action. Chichester, England: John Wiley and Sons; 1991:615637.Google Scholar
16.Jacobs, D, Silverstone, T. Dextroamphetamine-induced arousal in human subjects as a model for mania. Psychol Med. 1986;16:323329.CrossRefGoogle Scholar
17.Angrist, B. Amphetamine psychosis: clinical variations of the syndrome. In: Amphetamine and Its Analogues. San Diego, Calif: Academic Press; 1994:387414.Google Scholar
18.Smith, RE, Haroutunian, V, Davis, KL, Meador-Woodruff, JH. Vesicular glutamate transporter transcript expression in the thalamus in schizophrenia. Neuroreport. 2001;12:28852887.CrossRefGoogle ScholarPubMed
19.Meador-Woodruff, JH, Davis, KL, Haroutunian, V. Abnormal kainate receptor expression in prefrontal cortex in schizophrenia. Neuropsychopharmacol. 2001;24:545552.CrossRefGoogle ScholarPubMed
20.Mimics, K, Middleton, FA, Marquez, A, Lewis, DA, Levitt, P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron. 2000;28:5367.Google Scholar
21.Mimics, K, Middleton, FA, Stanwood, GD, Lewis, DA, Levitt, P. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry. 2001;6:293301.Google Scholar
22.Mimics, K, Middleton, FA, Lewis, DA, Levitt, P. Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse. Trends Neurosci. 2001;24:479486.Google Scholar
23.Hakak, Y, Walker, JR, Li, C, et al.Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A. 2001;98:47464751.CrossRefGoogle ScholarPubMed
24.Lewohl, JM, Dodd, PR, Mayfield, RD, Harris, RA. Application of DNA microarrays to study human alcoholism. J Biomed Sci. 2001;8:2836.CrossRefGoogle ScholarPubMed
25.Lewohl, JM, Wang, L, Miles, MF, et al.Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res. 2000;24:18731882.CrossRefGoogle ScholarPubMed
26.Niculescu, AB 3rd, Segal, DS, Kuczenski, R, et al.Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach. Physiol Genomics. 2000;4:8391.CrossRefGoogle ScholarPubMed
27.Yoon, IS, Li, PP, Siu, KP, et al.Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder. Mol Psychiatry. 2001;6:678683.CrossRefGoogle ScholarPubMed
28.Yoon, IS, Li, PP, Siu, KP, et al.Altered TRPC7 gene expression in bipolar-I disorder. Biol Psychiatry. 2001;50:620626.CrossRefGoogle ScholarPubMed
29.Niculescu, AB 3rd, Kelsoe, JR. Convergent functional genomics: application to bipolar disorder. Ann Med. 2001;33:263271.CrossRefGoogle ScholarPubMed
30.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;98:585590.CrossRefGoogle ScholarPubMed
31.Niculescu, AB 3rd, Akiskal, HS. Proposed endophenotypes of dysthymia: evolutionary, clinical and pharmacogenomic considerations. Mol Psychiatry. 2001;6:363366.CrossRefGoogle ScholarPubMed
32.Freedman, R, Coon, H, Myles-Worsley, M, et al.Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci U S A. 1997;94:587592.CrossRefGoogle ScholarPubMed
33.Myles-Worsley, M, Coon, H, McDowell, J, et al.Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families. Am J Med Genet. 1999;88:544550.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
34.Turecki, G, Grof, P, Grof, E, et al.Mapping susceptibility genes for bipolar disorder: a pharmacogenetic approach based on excellent response to lithium. Mol Psychiatry. 2001;6:570578.CrossRefGoogle ScholarPubMed