Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2011 Apr 6;27(2):123–133. doi: 10.1007/s12264-011-1203-5

Brain expression quantitative trait locus mapping informs genetic studies of psychiatric diseases

脑组织的表达数量性状遗传位点定位方法解析精神疾病遗传基础

Chunyu Liu 1,✉
PMCID: PMC3074249  NIHMSID: NIHMS279284  PMID: 21441974

Abstract

Genome-wide association study (GWAS) can be used to identify genes that increase the risk of psychiatric diseases. However, much of the disease heritability is still unexplained, suggesting that there are genes to be discovered. Functional annotation of the genetic variants may increase the power of GWAS to identify disease genes, by providing prior information that can be used in Bayesian analysis or in reducing the number of tests. Expression quantitative trait loci (eQTLs) are genomic loci that regulate gene expression. Genetic mapping of eQTLs can help reveal novel functional effects of thousands of single nucleotide polymorphisms (SNPs). The present review mainly focused on the current knowledge on brain eQTL mapping, and discussed some major methodological issues and their possible solutions. The frequently ignored problems of batch effects, covariates, and multiple testing were emphasized, since they can lead to false positives and false negatives. The future application of eQTL data in GWAS analysis was also discussed.

Keywords: genome-wide association study, brain, psychiatric diseases, expression quantitative trait loci, genetics, single nucleotide polymorphism

References

  • [1].Weissman M.M., Bland R.C., Canino G.J., Faravelli C., Greenwald S., Hwu H.G., et al. Cross-national epidemiology of major depression and bipolar disorder. JAMA. 1996;276(4):293–299. doi: 10.1001/jama.276.4.293. [DOI] [PubMed] [Google Scholar]
  • [2].McGrath J., Saha S., Chant D., Welham J. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67–76. doi: 10.1093/epirev/mxn001. [DOI] [PubMed] [Google Scholar]
  • [3].Piletz J.E., Zhang X., Ranade R., Liu C. Database of genetic studies of bipolar disorder. Psychiatr Genet. 2010;21(2):57–68. doi: 10.1097/YPG.0b013e328341a346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].International Schizophrenia Consortium. Purcell S.M., Wray N.R., Stone J.L., Visscher P.M., O’Donovan M.C., et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460(7256):748–752. doi: 10.1038/nature08185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Ferreira M.A., O’Donovan M.C., Meng Y.A., Jones I.R., Ruderfer D.M., Jones L., et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008;40(9):1056–1058. doi: 10.1038/ng.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Williams HJ, Norton N, Dwyer S, Moskvina V, Nikolov I, Carroll L, et al. Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder. Mol Psychiatry 2010. [Epub ahead of print] [DOI] [PMC free article] [PubMed]
  • [7].Liu Y., Blackwood D.H., Caesar S., de Geus E.J., Farmer A., Ferreira M.A., et al. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry. 2011;16(1):2–4. doi: 10.1038/mp.2009.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Psychiatric G.W.A.S. Consortium Steering Committee. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry. 2009;14(1):10–17. doi: 10.1038/mp.2008.126. [DOI] [PubMed] [Google Scholar]
  • [9].Vineis P., Pearce N. Missing heritability in genome-wide association study research. Nat Rev Genet. 2010;11(8):589. doi: 10.1038/nrg2809-c2. [DOI] [PubMed] [Google Scholar]
  • [10].Eichler E.E., Flint J., Gibson G., Kong A., Leal S.M., Moore J.H., et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010;11(6):446–450. doi: 10.1038/nrg2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Goldstein D.B. Common genetic variation and human traits. N Engl J Med. 2009;360(17):1696–1698. doi: 10.1056/NEJMp0806284. [DOI] [PubMed] [Google Scholar]
  • [12].Sebat J., Levy D.L., McCarthy S.E. Rare structural variants in schizophrenia: one disorder, multiple mutations, one mutation, multiple disorders. Trends Genet. 2009;25(12):528–535. doi: 10.1016/j.tig.2009.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Guilmatre A., Dubourg C., Mosca A.L., Legallic S., Goldenberg A., Drouin-Garraud V., et al. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Arch Gen Psychiatry. 2009;66(9):947–956. doi: 10.1001/archgenpsychiatry.2009.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Hampe J., Franke A., Rosenstiel P., Till A., Teuber M., Huse K., et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39(2):207–211. doi: 10.1038/ng1954. [DOI] [PubMed] [Google Scholar]
  • [15].Cantor R.M., Lange K., Sinsheimer J.S. Prioritizing GWAS results: A review of statistical methods and recommendations for their application. Am J Hum Genet. 2010;86(1):6–22. doi: 10.1016/j.ajhg.2009.11.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Ng P.C., Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31(13):3812–3814. doi: 10.1093/nar/gkg509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Ramensky V., Bork P., Sunyaev S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 2002;30(17):3894–3900. doi: 10.1093/nar/gkf493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Jegga A.G., Gowrisankar S., Chen J., Aronow B.J. PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease. Nucleic Acids Res. 2007;35:D700–D706. doi: 10.1093/nar/gkl826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Hindorff L.A., Sethupathy P., Junkins H.A., Ramos E.M., Mehta J.P., Collins F.S., et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009;106(23):9362–9367. doi: 10.1073/pnas.0903103106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Friedman R.C., Farh K.K., Burge C.B., Bartel D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105. doi: 10.1101/gr.082701.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Gaidatzis D., van N.E., Hausser J., Zavolan M. Inference of miRNA targets using evolutionary conservation and pathway analysis. BMC Bioinformatics. 2007;8:69. doi: 10.1186/1471-2105-8-69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Kertesz M., Iovino N., Unnerstall U., Gaul U., Segal E. The role of site accessibility in microRNA target recognition. Nat Genet. 2007;39(10):1278–1284. doi: 10.1038/ng2135. [DOI] [PubMed] [Google Scholar]
  • [23].Lall S., Grun D., Krek A., Chen K., Wang Y.L., Dewey C.N., et al. A genome-wide map of conserved microRNA targets in C. elegans. Curr Biol. 2006;16(5):460–471. doi: 10.1016/j.cub.2006.01.050. [DOI] [PubMed] [Google Scholar]
  • [24].Stark A., Brennecke J., Bushati N., Russell R.B., Cohen S.M. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell. 2005;123(6):1133–1146. doi: 10.1016/j.cell.2005.11.023. [DOI] [PubMed] [Google Scholar]
  • [25].Rockman M.V., Kruglyak L. Genetics of global gene expression. Nat Rev Genet. 2006;7(11):862–872. doi: 10.1038/nrg1964. [DOI] [PubMed] [Google Scholar]
  • [26].Schwartz D. Genetic studies on mutant enzymes in maize. III. Control of gene action in the synthesis of pH 7.5 Esterase. Genetics. 1962;47(11):1609–1615. doi: 10.1093/genetics/47.11.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Damerval C., Maurice A., Josse J.M., de Vienne D. Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression. Genetics. 1994;137(1):289–301. doi: 10.1093/genetics/137.1.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Jansen R.C., Nap J.P. Genetical genomics: the added value from segregation. Trends Genet. 2001;17(7):388–391. doi: 10.1016/S0168-9525(01)02310-1. [DOI] [PubMed] [Google Scholar]
  • [29].Cheung V.G., Spielman R.S. Genetics of human gene expression: mapping DNA variants that influence gene expression. Nat Rev Genet. 2009;10(9):595–604. doi: 10.1038/nrg2630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].Cheung V.G., Spielman R.S., Ewens K.G., Weber T.M., Morley M., Burdick J.T. Mapping determinants of human gene expression by regional and genome-wide association. Nature. 2005;437(7063):1365–1369. doi: 10.1038/nature04244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [31].Monks S.A., Leonardson A., Zhu H., Cundiff P., Pietrusiak P., Edwards S., et al. Genetic inheritance of gene expression in human cell lines. Am J Hum Genet. 2004;75(6):1094–1105. doi: 10.1086/426461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Morley M., Molony C.M., Weber T.M., Devlin J.L., Ewens K.G., Spielman R.S., et al. Genetic analysis of genome-wide variation in human gene expression. Nature. 2004;430(7001):743–747. doi: 10.1038/nature02797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Storey J.D., Madeoy J., Strout J.L., Wurfel M., Ronald J., Akey J.M. Gene-expression variation within and among human populations. Am J Hum Genet. 2007;80(3):502–509. doi: 10.1086/512017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Stranger B.E., Forrest M.S., Clark A.G., Minichiello M.J., Deutsch S., Lyle R., et al. Genome-wide associations of gene expression variation in humans. PLoS Genet. 2005;1(6):695–704. doi: 10.1371/journal.pgen.0010078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Stranger B.E., Forrest M.S., Dunning M., Ingle C.E., Beazley C., Thorne N., et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science. 2007;315(5813):848–853. doi: 10.1126/science.1136678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Veyrieras J.B., Kudaravalli S., Kim S.Y., Dermitzakis E.T., Gilad Y., Stephens M., et al. High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genet. 2008;4(10):e1000214. doi: 10.1371/journal.pgen.1000214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [37].Zhang W., Duan S., Kistner E.O., Bleibel W.K., Huang R.S., Clark T.A., et al. Evaluation of genetic variation contributing to differences in gene expression between populations. Am J Hum Genet. 2008;82(3):631–640. doi: 10.1016/j.ajhg.2007.12.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Schadt E.E., Molony C., Chudin E., Hao K., Yang X., Lum P.Y., et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6(5):1020–1032. doi: 10.1371/journal.pbio.0060107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Wheeler H.E., Metter E.J., Tanaka T., Absher D., Higgins J., Zahn J.M., et al. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. PLoS Genet. 2009;5(10):e1000685. doi: 10.1371/journal.pgen.1000685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Dixon A.L., Liang L., Moffatt M.F., Chen W., Heath S., Wong K.C., et al. A genome-wide association study of global gene expression. Nat Genet. 2007;39(10):1202–1207. doi: 10.1038/ng2109. [DOI] [PubMed] [Google Scholar]
  • [41].Moffatt M.F., Kabesch M., Liang L., Dixon A.L., Strachan D., Heath S., et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448(7152):470–473. doi: 10.1038/nature06014. [DOI] [PubMed] [Google Scholar]
  • [42].Emilsson V., Thorleifsson G., Zhang B., Leonardson A.S., Zink F., Zhu J., et al. Genetics of gene expression and its effect on disease. Nature. 2008;452(7186):423–428. doi: 10.1038/nature06758. [DOI] [PubMed] [Google Scholar]
  • [43].Heinzen E.L., Ge D., Cronin K.D., Maia J.M., Shianna K.V., Gabriel W.N., et al. Tissue-specific genetic control of splicing: implications for the study of complex traits. PLoS Biol. 2008;6(12):2869–2879. doi: 10.1371/journal.pbio.1000001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Liu C., Cheng L., Badner J.A., Zhang D., Craig D.W., Redman M., et al. Whole-genome association mapping of gene expression in the human prefrontal cortex. Mol Psychiatry. 2010;15(8):779–784. doi: 10.1038/mp.2009.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Myers A.J., Gibbs J.R., Webster J.A., Rohrer K., Zhao A., Marlowe L., et al. A survey of genetic human cortical gene expression. Nat Genet. 2007;39(12):1494–1499. doi: 10.1038/ng.2007.16. [DOI] [PubMed] [Google Scholar]
  • [46].Webster J.A., Gibbs J.R., Clarke J., Ray M., Zhang W., Holmans P., et al. Genetic control of human brain transcript expression in Alzheimer disease. Am J Hum Genet. 2009;84(4):445–458. doi: 10.1016/j.ajhg.2009.03.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [47].Iwamoto K., Bundo M., Kato T. Altered expression of mitochondriarelated genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet. 2005;14(2):241–253. doi: 10.1093/hmg/ddi022. [DOI] [PubMed] [Google Scholar]
  • [48].Mexal S., Berger R., Adams C.E., Ross R.G., Freedman R., Leonard S. Brain pH has a significant impact on human postmortem hippocampal gene expression profiles. Brain Res. 2006;1106(1):1–11. doi: 10.1016/j.brainres.2006.05.043. [DOI] [PubMed] [Google Scholar]
  • [49].Johnson W.E., Li C., Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118–127. doi: 10.1093/biostatistics/kxj037. [DOI] [PubMed] [Google Scholar]
  • [50].Leek J.T., Storey J.D. Capturing heterogeneity in gene expression studies by surrogate variable analysis. PLoS Genet. 2007;3(9):1724–1735. doi: 10.1371/journal.pgen.0030161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [51].Modrek B., Resch A., Grasso C., Lee C. Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res. 2001;29(13):2850–2859. doi: 10.1093/nar/29.13.2850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [52].Johnson J.M., Castle J., Garrett-Engele P., Kan Z., Loerch P.M., Armour C.D., et al. Genome-wide survey of human alternative premRNA splicing with exon junction microarrays. Science. 2003;302(5653):2141–2144. doi: 10.1126/science.1090100. [DOI] [PubMed] [Google Scholar]
  • [53].Clark T.A., Schweitzer A.C., Chen T.X., Staples M.K., Lu G., Wang H., et al. Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biol. 2007;8(4):R64. doi: 10.1186/gb-2007-8-4-r64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [54].Johnson M.B., Kawasawa Y.I., Mason C.E., Krsnik Z., Coppola G., Bogdanovic D., et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron. 2009;62(4):494–509. doi: 10.1016/j.neuron.2009.03.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [55].Xu Q., Modrek B., Lee C. Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res. 2002;30(17):3754–3766. doi: 10.1093/nar/gkf492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [56].Kwan T., Benovoy D., Dias C., Gurd S., Serre D., Zuzan H., et al. Heritability of alternative splicing in the human genome. Genome Res. 2007;17(8):1210–1218. doi: 10.1101/gr.6281007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [57].Nembaware V., Lupindo B., Schouest K., Spillane C., Scheffler K., Seoighe C. Genome-wide survey of allele-specific splicing in humans. BMC Genomics. 2008;9:265. doi: 10.1186/1471-2164-9-265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [58].Montgomery S.B., Sammeth M., Gutierrez-Arcelus M., Lach R.P., Ingle C., Nisbett J., et al. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature. 2010;464(7289):773–777. doi: 10.1038/nature08903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [59].Pickrell J.K., Marioni J.C., Pai A.A., Degner J.F., Engelhardt B.E., Nkadori E., et al. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature. 2010;464(7289):768–772. doi: 10.1038/nature08872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [60].Young J.I., Hong E.P., Castle J.C., Crespo-Barreto J., Bowman A.B., Rose M.F., et al. Regulation of RNA splicing by the methylationdependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci U S A. 2005;102(49):17551–17558. doi: 10.1073/pnas.0507856102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [61].Nakata K., Lipska B.K., Hyde T.M., Ye T., Newburn E.N., Morita Y., et al. DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Proc Natl Acad Sci U S A. 2009;106(37):15873–15878. doi: 10.1073/pnas.0903413106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [62].Mortazavi A., Williams B.A., McCue K., Schaeffer L., Wold B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008;5(7):621–628. doi: 10.1038/nmeth.1226. [DOI] [PubMed] [Google Scholar]
  • [63].Schroeder A., Mueller O., Stocker S., Salowsky R., Leiber M., Gassmann M., et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;7:3. doi: 10.1186/1471-2199-7-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [64].Alberts R., Terpstra P., Li Y., Breitling R., Nap J.P., Jansen R.C. Sequence polymorphisms cause many false cis eQTLs. PLoS One. 2007;2(7):e622. doi: 10.1371/journal.pone.0000622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [65].Duan S., Zhang W., Bleibel W.K., Cox N.J., Dolan M.E. SNPin-Probe_1.0: a database for filtering out probes in the Affymetrix GeneChip human exon 1.0 ST array potentially affected by SNPs. Bioinformation. 2008;2(10):469–470. doi: 10.6026/97320630002469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [66].Gamazon E.R., Zhang W., Dolan M.E., Cox N.J. Comprehensive survey of SNPs in the Affymetrix exon array using the 1000 Genomes dataset. PLoS One. 2010;5(2):e9366. doi: 10.1371/journal.pone.0009366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Nagalakshmi U., Wang Z., Waern K., Shou C., Raha D., Gerstein M., et al. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320(5881):1344–1349. doi: 10.1126/science.1158441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [68].Marioni J.C., Mason C.E., Mane S.M., Stephens M., Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008;18(9):1509–1517. doi: 10.1101/gr.079558.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [69].Wang Z., Gerstein M., Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10(1):57–63. doi: 10.1038/nrg2484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [70].Heap G.A., Yang J.H., Downes K., Healy B.C., Hunt K.A., Bockett N., et al. Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum Mol Genet. 2010;19(1):122–134. doi: 10.1093/hmg/ddp473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [71].Stevens C.F. Neuronal diversity: too many cell types for comfort? Curr Biol. 1998;8(20):R708–R710. doi: 10.1016/S0960-9822(98)70454-3. [DOI] [PubMed] [Google Scholar]
  • [72].Giger T., Khaitovich P., Somel M., Lorenc A., Lizano E., Harris L.W., et al. Evolution of neuronal and endothelial transcriptomes in primates. Genome Biol Evol. 2010;2:284–292. doi: 10.1093/gbe/evq018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [73].Cahoy J.D., Emery B., Kaushal A., Foo L.C., Zamanian J.L., Christopherson K.S., et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008;28(1):264–278. doi: 10.1523/JNEUROSCI.4178-07.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [74].Nielsen J.A., Maric D., Lau P., Barker J.L., Hudson L.D. Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling. J Neurosci. 2006;26(39):9881–9891. doi: 10.1523/JNEUROSCI.2246-06.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [75].Bachoo R.M., Kim R.S., Ligon K.L., Maher E.A., Brennan C., Billings N., et al. Molecular diversity of astrocytes with implications for neurological disorders. Proc Natl Acad Sci U S A. 2004;101(22):8384–8389. doi: 10.1073/pnas.0402140101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [76].Sugino K., Hempel C.M., Miller M.N., Hattox A.M., Shapiro P., Wu C., et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat Neurosci. 2006;9(1):99–107. doi: 10.1038/nn1618. [DOI] [PubMed] [Google Scholar]
  • [77].Bernard R., Kerman I.A., Meng F., Evans S.J., Amrein I., Jones E.G., et al. Gene expression profiling of neurochemically defined regions of the human brain by in situ hybridization-guided laser capture microdissection. J Neurosci Methods. 2009;178(1):46–54. doi: 10.1016/j.jneumeth.2008.11.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [78].Luo L., Salunga R.C., Guo H., Bittner A., Joy K.C., Galindo J.E., et al. Gene expression profiles of laser-captured adjacent neuronal subtypes. Nat Med. 1999;5(1):117–122. doi: 10.1038/4806. [DOI] [PubMed] [Google Scholar]
  • [79].Grimm J., Mueller A., Hefti F., Rosenthal A. Molecular basis for catecholaminergic neuron diversity. Proc Natl Acad Sci U S A. 2004;101(38):13891–13896. doi: 10.1073/pnas.0405340101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [80].Chung C.Y., Seo H., Sonntag K.C., Brooks A., Lin L., Isacson O. Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum Mol Genet. 2005;14(13):1709–1725. doi: 10.1093/hmg/ddi178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [81].Greene J.G., Dingledine R., Greenamyre J.T. Gene expression profiling of rat midbrain dopamine neurons: implications for selective vulnerability in Parkinsonism. Neurobiol Dis. 2005;18(1):19–31. doi: 10.1016/j.nbd.2004.10.003. [DOI] [PubMed] [Google Scholar]
  • [82].Rong Y., Wang T., Morgan J.I. Identification of candidate Purkinje cell-specific markers by gene expression profiling in wild-type and pcd(3J) mice. Brain Res Mol Brain Res. 2004;132(2):128–145. doi: 10.1016/j.molbrainres.2004.10.015. [DOI] [PubMed] [Google Scholar]
  • [83].Roth R.B., Hevezi P., Lee J., Willhite D., Lechner S.M., Foster A.C., et al. Gene expression analyses reveal molecular relationships among 20 regions of the human CNS. Neurogenetics. 2006;7(2):67–80. doi: 10.1007/s10048-006-0032-6. [DOI] [PubMed] [Google Scholar]
  • [84].Sandberg R., Yasuda R., Pankratz D.G., Carter T.A., Del Rio J.A., Wodicka L., et al. Regional and strain-specific gene expression mapping in the adult mouse brain. Proc Natl Acad Sci U S A. 2000;97(20):11038–11043. doi: 10.1073/pnas.97.20.11038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [85].Stansberg C., Vik-Mo A.O., Holdhus R., Breilid H., Srebro B., Petersen K., et al. Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation. BMC Genomics. 2007;8:94. doi: 10.1186/1471-2164-8-94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [86].Khaitovich P., Muetzel B., She X.W., Lachmann M., Hellmann I., Dietzsch J., et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Research. 2004;14(8):1462–1473. doi: 10.1101/gr.2538704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [87].Oldham M.C., Konopka G., Iwamoto K., Langfelder P., Kato T., Horvath S., et al. Functional organization of the transcriptome in human brain. Nat Neurosci. 2008;11(11):1271–1282. doi: 10.1038/nn.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [88].Nicolae D.L., Gamazon E., Zhang W., Duan S., Dolan M.E., Cox N.J. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet. 2010;6(4):e1000888. doi: 10.1371/journal.pgen.1000888. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES