Synaptogenomics

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Synaptogenomics' is a concept that has been proposed in order to define the systematic analysis of variations in genes encoding proteins involved in synaptic plasticity mechanisms. 
It has been proposed that it will be helpful for the identification of novel causal and susceptibility genes for neuropsychiatric disorders and other neurocognitive phenotypes. There are more than 220 articles in PubMed (the main database of peer-reviewed scientific papers in biomedical research) describing results of explorations of polymorphisms in several synaptic genes (such as GRIN1, GRIN2B, CREB1, SNAP25, BDNF, among others) in different neuropsychiatric disorders (such as schizophrenia, bipolar disorder, major depression, autism, ADHD, among others). These analyses are important in the context of many previous investigations that show that many of these disorders are related to dysfunction of the synaptic plasticity mechanisms (called "synaptopathies") and that have strong hereditary components, which can be explored with the powerful methodological tools of the genomics field and other non-biased systematic approaches.


See also
Genomics


References

Li JY, Plomann M, Brundin P. Huntington's disease: a synaptopathy? Trends Mol Med. 2003 Oct;9(10):414-20.

Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, Newsom-Davis J, Burke G, Fawcett P, Motomura M, Müller JS, Lochmüller H, Slater C, Vincent A, Yamanashi Y. Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science. 2006 Sep 29;313(5795):1975-8.

Palace J, Lashley D, Newsom-Davis J, Cossins J, Maxwell S, Kennett R, Jayawant S, Yamanashi Y, Beeson D. Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain. 2007 Jun;130(Pt 6):1507-15.

Specht D, Tom Dieck S, Ammermüller J, Regus-Leidig H, Gundelfinger ED, Brandstätter JH. Structural and functional remodeling in the retina of a mouse with a photoreceptor synaptopathy: plasticity in the rod and degeneration in the cone system. Eur J Neurosci. 2007 Nov;26(9):2506-15.

Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan SR, Malloy MP, Chubb JE, Huston E, Baillie GS, Thomson PA, Hill EV, Brandon NJ, Rain JC, Camargo LM, Whiting PJ, Houslay MD, Blackwood DH, Muir WJ, Porteous DJ. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science. 2005 Nov 18;310(5751):1187-91.

Seripa D, Matera MG, Franceschi M, Bizzarro A, Paris F, Cascavilla L, Rinaldi M, Panza F, Solfrizzi V, Daniele A, Masullo C, Dallapiccola B, Pilotto A. Association analysis of GRIN2B, encoding N-methyl-D-aspartate receptor 2B subunit, and Alzheimer's disease. Dement Geriatr Cogn Disord. 2008;25(3):287-92.

Liou YJ, Wang YC, Chen JY, Bai YM, Lin CC, Liao DL, Chen TT, Chen ML, Mo GH, Lai IC. Association analysis of polymorphisms in the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GRIN2B) gene and tardive dyskinesia in schizophrenia. Psychiatry Res. 2007 Dec 3;153(3):271-5.

Arning L, Saft C, Wieczorek S, Andrich J, Kraus PH, Epplen JT. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease in a sex-specific manner. Hum Genet. 2007 Sep;122(2):175-82.

Tsai SJ, Hong CJ, Cheng CY, Liao DL, Liou YJ. Association study of polymorphisms in post-synaptic density protein 95 (PSD-95) with schizophrenia. J Neural Transm. 2007;114(4):423-6.

Tang J, Chen X, Xu X, Wu R, Zhao J, Hu Z, Xia K. Significant linkage and association between a functional (GT)n polymorphism in promoter of the N-methyl-D-aspartate receptor subunit gene (GRIN2A) and schizophrenia. Neurosci Lett. 2006 Nov 27;409(1):80-2.

Perlis RH, Purcell S, Fagerness J, Cusin C, Yamaki L, Fava M, Smoller JW. Clinical and genetic dissection of anger expression and CREB1 polymorphisms in major depressive disorder. Biol Psychiatry. 2007 Sep 1;62(5):536-40.

Bartsch O, Schmidt S, Richter M, Morlot S, Seemanová E, Wiebe G, Rasi S. DNA sequencing of CREBBP demonstrates mutations in 56% of patients with Rubinstein-Taybi syndrome (RSTS) and in another patient with incomplete RSTS. Hum Genet. 2005 Sep;117(5):485-93.

Burcescu I, Wigg K, King N, Vetró A, Kiss E, Katay L, Kennedy JL, Kovacs M, Barr CL. Association study of CREB1 and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 5;137B(1):45-50.

Hamilton SP, Slager SL, Mayo D, Heiman GA, Klein DF, Hodge SE, Fyer AJ, Weissman MM, Knowles JA. Investigation of polymorphisms in the CREM gene in panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):111-5.

Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy JL, Barr CL. The SNAP25 gene as a susceptibility gene contributing to attention-deficit hyperactivity disorder. Mol Psychiatry. 2005 Nov;10(11):998-1005, 973.

Mill J, Richards S, Knight J, Curran S, Taylor E, Asherson P. Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD. Mol Psychiatry. 2004 Aug;9(8):801-10.

Tan HY, Nicodemus KK, Chen Q, Li Z, Brooke JK, Honea R, Kolachana BS, Straub RE, Meyer-Lindenberg A, Sei Y, Mattay VS, Callicott JH, Weinberger DR. Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans. J Clin Invest. 2008 Jun;118(6):2200-8.

Gratacòs M, González JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry. 2007 Apr 1;61(7):911-22.

Inoue S, Imamura A, Okazaki Y, Yokota H, Arai M, Hayashi N, Furukawa A, Itokawa M, Oishi M. Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144B(3):332-40.

Wahlstrom D, White T, Hooper CJ, Vrshek-Schallhorn S, Oetting WS, Brott MJ, Luciana M. Variations in the catechol O-methyltransferase polymorphism and prefrontally guided behaviors in adolescents. Biol Psychiatry. 2007 Mar 1;61(5):626-32.

Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell S, Aldinger KA, Kirby A, Morley CP, McGann L, Gentile KL, Waggoner SG, Medeiros HM, Carvalho C, Macedo A, Albus M, Maier W, Trixler M, Eichhammer P, Schwab SG, Wildenauer DB, Azevedo MH, Pato MT, Pato CN, Daly MJ, Sklar P. Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. Mol Psychiatry. 2005 Dec;10(12):1074-88.

Grant SG, Marshall MC, Page KL, Cumiskey MA, Armstrong JD. Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases. Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R225-34.

Lee HJ, Song JY, Kim JW, Jin SY, Hong MS, Park JK, Chung JH, Shibata H, Fukumaki Y. Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia. Behav Brain Funct. 2005 Aug 31;1:15.

Lachman HM, Stopkova P, Rafael MA, Saito T. Association of schizophrenia in African Americans to polymorphism in synapsin III gene. Psychiatr Genet. 2005 Jun;15(2):127-32.

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