Abstract
Genetic variations might contribute to differences in protein activities and gene expression levels observed in complex genetic traits, like neuropsychiatric disease. This finding motivated the development of original approaches using expression studies to guide the finding of new genetic variations. We extended this approach to new genes selected from microarrays studies of brain samples of patients with Alzheimer’s disease, major depressive disorder, bipolar affective disorder, and sporadic Creutzfeldt–Jakob disease. The CLCbio Workbench Combined® version 3.6.2 was initially used to build expression sites tags (ESTs) and mRNA files retrieved, respectively, from the Goldenpath (UCSC) and NCBI databases and latter to perform multiple batches of Smith–Waterman alignments. The total of 438 ESTs sequences were selected after proper stringent parameters were applied to the first set of mismatches. The annotation revealed various classes of variations, most of them deletions ranging from 1 to 10 pb. These deletions were present in coding regions, 5′ and 3′ UTR regions. Deletions are often associated to major genetic syndromes with dysmorphic features; however, recent studies show that common microdeletions might be highly associated with common neuropsychiatric disorders.
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References
Aguzzi A, Baumann F, Bremer J (2008) The Prion’s elusive reason for being. Annu Rev Neurosci 31:439–477
Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW (2004) Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci 101:2173–2178
Choudary PV, Molnar M, Evans SJ et al (2005) Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci USA 102:15653–15658
Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ (2002) Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 70:462–473
Conrad DF, Pinto D, Redon R et al (2009) Origins and functional impact of copy number variation in the human genome. Nature doi:10.1038/nature08516. 14 August 2009
Coppola G, Karydas A, Rademakers R et al (2008) Gene expression study on peripheral blood identifies progranulin mutations. Ann Neurol 64:92–96
Ferrarese C, Tremolizzo L, Rigoldi M et al (2001) Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease. Neurol Sci 22:65–66
Forment J, Gilbert F, Robles A, Conejero V, Nuez F, Blanca JM (2008) EST2uni: an open, parallel tool for automated EST analysis and database creation, with a data mining web interface and microarray expression data integration. BMC Bioinformatics 9:5–15
Kerber AR, Hepp D, Passos DT, de Azevedo Weimer T (2008) Polymorphisms of two indels at the PRNP gene in three beef cattle herds. Biochem Genet 46:1–7
Lemos RR, Castelletti CH, Lima Filho JL, Marques ET, Oliveira JR (2009) In silico identification of new genetic variations as potential risk factors for Alzheimer´s Disease in a Microarray oriented simulation. J Mol Neurosci 39:242–247
Mao G, Pan X, Zhu BB et al (2007) Identification and characterization of OGG1 mutation in patients with Alzheimer’s disease. Nucleic Acids Res 35:2759–2766
McCullumsmith RE, Meador-Woodruff JH (2002) Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology 26:368–375
Mead S, Poulter M, Uphill J et al (2009) Genetic risk factors for variant Creutzfeldt–Jakob disease: a genome-wide association study. Lancet Neurol 8:57–66
Miller JA, Oldham MC, Geschwind DH (2008) A systems level analysis of transcriptional changes in Alzheimer’s disease and normal aging. J Neurosci 28:1410–1420
Sanacora G, Zarate CA, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature 7:426–437
Stefansson D, Rujescu D, Cichon S et al (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455:232–236
Stein LD (2008) Towards a cyberinfrastructure for the biological sciences: progress, visions and challenges. Nat Rev Genet 9:678–688
Useche FJ, Gao G, Harafey M, Rafalski A (2001) High-throughput identification, database storage and analysis of SNPs in ESTs sequences. Genome Informatics 12:194–203
Walsh T, Mcclellan JM, Mccarthy SE et al (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539–543
Weeraratna AT, Kalehua A, DeLeon I et al (2007) Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues. Exp Cell Res 3:450–461
Xiang W, Windl O, Westner IM et al (2005) Cerebral gene expression profiles in sporadic Creutzfeldt–Jakob disease. Ann Neurol 58:242–257
Yu CE, Dawson G, Munson J et al (2002) Presence of large deletions in kindreds with autism. Am J Hum Genet 71:100–115
Acknowledgments
We are greatly indebted to Henrique Castelletti and Aaron Rowe for technical support and manuscript review. This study received financial support from the following Brazilian funding agencies and academic bureaus: LIKA-JIKA, PROPESQ-UFPE, CAPES, CNPq, and FACEPE.
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Manuela Barbosa Rodrigues de Souza and Roberta Rodrigues de Lemos contributed equally to this work.
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de Souza, M.B.R., de Lemos, R.R., da Cunha, J.E.G. et al. Searching for New Genetic Risk Factors for Neuropsychiatric Disorders in Expression Databases. J Mol Neurosci 41, 193–197 (2010). https://doi.org/10.1007/s12031-009-9321-5
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DOI: https://doi.org/10.1007/s12031-009-9321-5