Skip to main content
SpringerLink
Log in
Book cover

Handbook of Neurochemistry and Molecular Neurobiology pp 91–106Cite as

G72/G30 in Neuropsychiatric Disorders

  • Reference work entry

  • 861 Accesses

Abstract:

G72 and G30 constitute a pair of primate-specific genes on complementary strands of human chromosomal 13q33. G72 is proposed to encode a protein that can activate d-amino acid oxidase (DAAO), therefore, named as d-aminoacid oxidase activator (DAOA) (Chumakov et al., 2002). This hypothesis about G72 and DAAO requires substantial further proof (see discussion later), and the “neutral” name G72 will be used here, although DAOA is widely used in the literature now. The G72/G30 gene is, at this time, one of the best supported loci for both schizophrenia (SZ) and bipolar disorder (BD) by independent datasets (Craddock et al., 2006; Detera-Wadleigh and McMahon, 2006). Here, we will describe the discovery of gene complex G72/G30, association studies with SZ and BD with a meta-analysis, as well as brief information about the biology of G72/G30.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

CD/MRV:

Common Disease/Multiple Rare Variants

DAAO:

d-amino acid oxidase

DAOA:

d-aminoacid oxidase activator

EST:

expression sequence tag

GEO:

Gene Expression Omnibus

MAF:

minor allele frequency

NIMH:

National Institute of Mental Health

NMDA:

N-methyl d-aspartate

RT-PCR:

reverse transcription-PCR

References

  • Badner JA, Gershon ES. 2002. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7: 405–411.

    Article  PubMed  CAS  Google Scholar 

  • Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KG. 2006. Development and validation of MIX: Comprehensive free software for meta-analysis of causal research data. BMC Med Res Methodol 6: 50.

    Article  PubMed  Google Scholar 

  • Berrettini WH. 2000. Susceptibility loci for bipolar disorder: Overlap with inherited vulnerability to schizophrenia. Biol Psychiatry 47: 245–251.

    Article  PubMed  CAS  Google Scholar 

  • Bertram L, McQueen MB, Mullin K, Blacker D, Tanzi RE. 2007. Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat Genet 39: 17–23.

    Article  PubMed  CAS  Google Scholar 

  • Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, et al. 1999. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 22: 231–238.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson A, Waters N, Carlsson ML. 1999. Neurotransmitter interactions in schizophrenia – therapeutic implications. Biol Psychiatry 46: 1388–1395.

    Article  PubMed  CAS  Google Scholar 

  • Chakravarti A. 1999. Population genetics – making sense out of sequence. Nat Genet 21: 56–60.

    Article  PubMed  CAS  Google Scholar 

  • Cho HJ, Meira-Lima I, Cordeiro Q, Michelon L, Sham P, et al. 2005. Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: A systematic review and meta-analysis. Mol Psychiatry 10: 771–781.

    Article  PubMed  CAS  Google Scholar 

  • Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, et al. 2002. Genetic and physiological data implicating the new human gene G72 and the gene for d-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 99: 13675–13680.

    Article  PubMed  CAS  Google Scholar 

  • Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, et al. 2004. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 305: 869–872.

    Article  PubMed  CAS  Google Scholar 

  • Cohen JC, Pertsemlidis A, Fahmi S, Esmail S, Vega GL, et al. 2006. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc Natl Acad Sci USA 103: 1810–1815.

    Article  PubMed  CAS  Google Scholar 

  • Coyle JT, Tsai G, Goff D. 2003. Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann N Y Acad Sci 1003: 318–327.

    Article  PubMed  CAS  Google Scholar 

  • Craddock N, Forty L. 2006. Genetics of affective (mood) disorders. Eur J Hum Genet 14: 660–668.

    Article  PubMed  CAS  Google Scholar 

  • Craddock N, O’Donovan MC, Owen MJ. 2005. The genetics of schizophrenia and bipolar disorder: Dissecting psychosis. J Med Genet 42: 193–204.

    Article  PubMed  CAS  Google Scholar 

  • Craddock N, O’Donovan MC, Owen MJ. 2006. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr Bull 32: 9–16.

    Article  PubMed  Google Scholar 

  • DePaulo JR Jr. 2004. Genetics of bipolar disorder: Where do we stand? Am J Psychiatry 161: 595–597.

    Article  PubMed  Google Scholar 

  • DerSimonian R, Laird N. 1986. Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.

    Article  PubMed  CAS  Google Scholar 

  • Detera-Wadleigh SD, McMahon FJ. 2006. G72/G30 in Schizophrenia and bipolar disorder: Review and meta-analysis. Biol Psychiatry 60: 106–114.

    Article  PubMed  CAS  Google Scholar 

  • Fearnhead NS, Wilding JL, Winney B, Tonks S, Bartlett S, et al. 2004. Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas. Proc Natl Acad Sci USA 101: 15992–15997.

    Article  PubMed  CAS  Google Scholar 

  • Feuk L, Carson AR, Scherer SW. 2006. Structural variation in the human genome. Nat Rev Genet 7: 85–97.

    Article  PubMed  CAS  Google Scholar 

  • Gershon ES. 2000. Bipolar illness and schizophrenia as oligogenic diseases: Implications for the future. Biol Psychiatry 47: 240–244.

    Article  PubMed  CAS  Google Scholar 

  • Goes FS, Zandi PP, Miao K, McMahon FJ, Steele J, et al. 2007. Mood-incongruent psychotic features in bipolar disorder: Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. Am J Psychiatry 164: 236–247.

    Article  PubMed  Google Scholar 

  • Goldberg TE, Straub RE, Callicott JH, Hariri A, Mattay VS, et al. 2006. The G72/G30 gene complex and cognitive abnormalities in schizophrenia. Neuropsychopharmacology 31: 2022–2032.

    Article  PubMed  CAS  Google Scholar 

  • Gottesman II, Gould TD. 2003. The endophenotype concept in psychiatry: Etymology and strategic intentions. Am J Psychiatry 160: 636–645.

    Article  PubMed  Google Scholar 

  • Hattori E, Liu C, Badner JA, Bonner TI, Christian SL, et al. 2003. Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series. Am J Hum Genet 72: 1131–1140.

    Article  PubMed  CAS  Google Scholar 

  • Javitt DC. 2001. Management of negative symptoms of schizophrenia. Curr Psychiatry Rep 3: 413–417.

    Article  PubMed  CAS  Google Scholar 

  • Johnson ME, Viggiano L, Bailey JA, Abdul-Rauf M, Goodwin G, et al. 2001. Positive selection of a gene family during the emergence of humans and African apes. Nature 413: 514–519.

    Article  PubMed  CAS  Google Scholar 

  • Kazeem GR, Farrall M. 2005. Integrating case-control and TDT studies. Ann Hum Genet 69: 329–335.

    Article  PubMed  CAS  Google Scholar 

  • Lander ES. 1996. The new genomics: Global views of biology. Science 274: 536–539.

    Article  PubMed  CAS  Google Scholar 

  • Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, et al. 2003. Genome scan meta-analysis of schizophrenia and bipolar disorder, Part 2: Schizophrenia. Am J Hum Genet 73: 34–48.

    Article  PubMed  CAS  Google Scholar 

  • Lin PI, Vance JM, Pericak-Vance MA, Martin ER. 2007. No gene is an island: The flip-flop phenomenon. Am J Hum Genet 80: 531–538.

    Article  PubMed  CAS  Google Scholar 

  • Lin S, Chakravarti A, Cutler DJ. 2004. Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies. Nat Genet 36: 1181–1188.

    Article  PubMed  CAS  Google Scholar 

  • Lindsley CW, Shipe WD, Wolkenberg SE, Theberge CR, Williams DL Jr, et al. 2006. Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia. Curr Top Med Chem 6: 771–785.

    Article  PubMed  CAS  Google Scholar 

  • Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. 2003. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33: 177–182.

    Article  PubMed  CAS  Google Scholar 

  • Ma J, Qin W, Wang XY, Guo TW, Bian L, et al. 2006. Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations. Mol Psychiatry 11: 479–487.

    Article  PubMed  CAS  Google Scholar 

  • Maier W, Hofgen B, Zobel A, Rietschel M. 2005. Genetic models of schizophrenia and bipolar disorder: Overlapping inheritance or discrete genotypes? Eur Arch Psychiatry Clin Neurosci 255: 159–166.

    Article  PubMed  Google Scholar 

  • Maier W, Zobel A, Kuhn KU. 2006. Clinical impact of recently detected susceptibility genes for schizophrenia. Dialogues Clin Neurosci 8: 79–84.

    PubMed  Google Scholar 

  • McGuffin P, Tandon K, Corsico A. 2003. Linkage and association studies of schizophrenia. Curr Psychiatry Rep 5: 121–127.

    Article  PubMed  Google Scholar 

  • McQueen MB, Devlin B, Faraone SV, Nimgaonkar VL, Sklar P, et al. 2005. Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q. Am J Hum Genet 77: 582–595.

    Article  PubMed  CAS  Google Scholar 

  • Meyer J, Johannssen K, Freitag CM, Schraut K, Teuber I, et al. 2005. Rare variants of the gene encoding the potassium chloride co-transporter 3 are associated with bipolar disorder. Int J Neuropsychopharmacol 8: 495–504.

    Article  PubMed  CAS  Google Scholar 

  • Meyer-Lindenberg A, Weinberger DR. 2006. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7: 818–827.

    Article  PubMed  CAS  Google Scholar 

  • Moghaddam B. 2003. Bringing order to the glutamate chaos in schizophrenia. Neuron 40: 881–884.

    Article  PubMed  CAS  Google Scholar 

  • Mohn AR, Gainetdinov RR, Caron MG, Koller BH. 1999. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98: 427–436.

    Article  PubMed  CAS  Google Scholar 

  • Molla G, Bernasconi M, Sacchi S, Pilone MS, Pollegioni L. 2006. Expression in Escherichia coli and in vitro refolding of the human protein pLG72. Protein Expr Purif 46: 150–155.

    Article  PubMed  CAS  Google Scholar 

  • Park N, Juo SH, Cheng R, Liu J, Loth JE, et al. 2004. Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry 9: 1091–1099.

    Article  PubMed  CAS  Google Scholar 

  • Potash JB, Zandi PP, Willour VL, Lan TH, Huo Y, et al. 2003. Suggestive linkage to chromosomal regions 13q31 and 22q12 in families with psychotic bipolar disorder. Am J Psychiatry 160: 680–686.

    Article  PubMed  Google Scholar 

  • Pritchard JK. 2001. Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69: 124–137.

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JK, Cox NJ. 2002. The allelic architecture of human disease genes: Common disease-common variant…or not? Hum Mol Genet 11: 2417–2423.

    Article  PubMed  CAS  Google Scholar 

  • Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, et al. 2006. Global variation in copy number in the human genome. Nature 444: 444–454.

    Article  PubMed  CAS  Google Scholar 

  • Reich DE, Lander ES. 2001. On the allelic spectrum of human disease. Trends Genet 17: 502–510.

    Article  PubMed  CAS  Google Scholar 

  • Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, et al. 2003. Genome scan meta-analysis of schizophrenia and bipolar disorder, Part 3: Bipolar disorder. Am J Hum Genet 73: 49–62.

    Article  PubMed  CAS  Google Scholar 

  • Wang WY, Barratt BJ, Clayton DG, Todd JA. 2005. Genome-wide association studies: Theoretical and practical concerns. Nat Rev Genet 6: 109–118.

    Article  PubMed  CAS  Google Scholar 

  • Wildenauer DB, Schwab SG, Maier W, Detera-Wadleigh SD. 1999. Do schizophrenia and affective disorder share susceptibility genes? Schizophr Res 39: 107–111.

    Article  PubMed  CAS  Google Scholar 

  • Williams NM, Green EK, MacGregor S, Dwyer S, Norton N, et al. 2006. Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. Arch Gen Psychiatry 63: 366–373.

    Article  PubMed  CAS  Google Scholar 

  • Zeggini E, Rayner W, Morris AP, Hattersley AT, Walker M, et al. 2005. An evaluation of HapMap sample size and tagging SNP performance in large-scale empirical and simulated data sets. Nat Genet 37: 1320–1322.

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Fejerman L, Luke A, Adeyemo A, Cooper RS. 2005. Haplotypes produced from rare variants in the promoter and coding regions of angiotensinogen contribute to variation in angiotensinogen levels. Hum Mol Genet 14: 639–643.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. S. Gershon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Daniel Javitt (Director) (Director)

  3. Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Joshua Kantrowitz

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this entry

Cite this entry

Shi, J., Cheng, L., Gershon, E.S., Liu, C. (2009). G72/G30 in Neuropsychiatric Disorders. In: Lajtha, A., Javitt, D., Kantrowitz, J. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30410-6_4

Download citation

Publish with us

Policies and ethics

Search

Navigation