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中华老年病研究电子杂志

中华老年病研究电子杂志 ›› 2016, Vol. 03 ›› Issue (04) : 23 -32. doi: 10.3877/cma.j.issn.2095-8757.2016.04.007

所属专题： 文献；

综述

RNA-Seq在老年神经退行性疾病研究中的应用
刘小利1, 严静2,†()   
  1. 1. 310013　杭州，浙江医院；310053　杭州，浙江中医药大学第二临床医学院
    2. 310013　杭州，浙江医院
  • 收稿日期:2016-11-01 出版日期:2016-11-28
  • 通信作者: 严静
  • 基金资助:
    浙江省科技厅公益项目(2015C33135)

Application of RNA-Seq in the study of neurodegenerative diseases

Xiaoli Liu1, Jing Yan2,†()   

  1. 1. Zhejiang Hospital, Hangzhou 310013, China; Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
    2. Zhejiang Hospital, Hangzhou 310013, China
  • Received:2016-11-01 Published:2016-11-28
  • Corresponding author: Jing Yan
  • About author:
    Corresponding author: Yan Jing, Email:
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引用本文：

刘小利, 严静. RNA-Seq在老年神经退行性疾病研究中的应用[J/OL]. 中华老年病研究电子杂志, 2016, 03(04): 23-32.

Xiaoli Liu, Jing Yan. Application of RNA-Seq in the study of neurodegenerative diseases[J/OL]. Chinese Journal of Geriatrics Research(Electronic Edition), 2016, 03(04): 23-32.

阿尔茨海默病及帕金森病是老年人最常见的两种神经退行性疾病，但其发病机制及治疗是研究的热点。随着高通量测序技术的进步及成本的下降，RNA-Seq也成为神经退行性疾病机制研究及生物标志物发现的有力手段。RNA-Seq相对于microarray具有高灵敏度、高准确性、高重复性以及噪声低等优势，在阿尔茨海默病及帕金森病研究中有较为广泛的应用，包括检测差异表达基因，可变剪接、新长链非编码RNA预测分析和miRNAs调控等，但是容易受病理复杂性及样本等因素影响。目前阿尔茨海默病及帕金森病转录组研究相比于癌症等还不够深入，在临床诊断及治疗应用还面临较大挑战。但是随着新技术及新方法的发展，RNA-Seq将进一步推动神经退行性相关疾病的研究和临床转化。

关键词: 阿尔茨海默病, 帕金森病, 神经退行性疾病, RNA-Seq, 差异表达基因, 可变剪接, IncRNA, miRNA

Alzheimer's disease(AD) and Parkinson's disease(PD) are the two most common neurodegenerative diseases of the aged, and the pathogenesis and treatment are the hot spots in the current study.With the advance of high-throughput sequencing technology and the decline of cost, RNA sequencing (RNA-Seq) has also become a powerful method for the neurodegenerative disease mechanism research and biomarker discovery. Compared with microarray,RNA-Seq has the advantages of high sensitivity, high accuracy, high repeatability and low noise, and has a wider application in the study of AD and PD, including detection of differentially expressed genes, alternative splicing, new lncRNA predictive analysis and miRNAs regulation. Influenced by the pathological complexity and specimens,the regulatory mechanism research of AD and PD is not deep enough,and we also face great challenge in clinical diagnosis and treatment application. But with the development of new technologies and methods, RNA-Seq will further promote the research and clinical transformation of neurodegenerative diseases.

Key words: Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, RNA-Seq, alternative splicing, lncRNA, miRNA
[1]
Fratiglioni L, De Ronchi D, Aguero-Torres H. Worldwide prevalence and incidence of dementia[J]. Drugs Aging, 1999, 15(5): 365-375.
[2]
Jorm AF, Dear KB, Burgess NM. Projections of future numbers of dementia cases in Australia with and without prevention[J]. Aust N Z J Psychiatry, 2005, 39(11-12): 959-963.
[3]
Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study[J]. Neuroepidemiology, 2007, 29(1-2): 125-132.
[4]
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes[J]. Acta Neuropathol, 1991, 82(4): 239-259.
[5]
de Lau LM, Breteler MM. Epidemiology of Parkinson's disease[J]. Lancet Neurol, 2006, 5(6): 525-535.
[6]
Zhang ZX, Roman GC, Hong Z, et al. Parkinson's disease in China: prevalence in Beijing, Xi'an, and Shanghai[J]. Lancet, 2005, 365(9459): 595-597.
[7]
Mandel S, Grunblatt E, Riederer P, et al. Gene expression profiling of sporic Parkinson's disease substantia nigra pars compacta reveals impairment of ubiquitin-proteasome subunits, SKP1A, aldehyde dehydrogenase, and chaperone HSC-70[J]. Ann N Y Acad Sci, 2005, 1053: 356-375.
[8]
Altar CA, Vawter MP, Ginsberg SD. Target identification for CNS diseases by transcriptional profiling[J]. Neuropsychopharmacology, 2009, 34(1): 18-54.
[9]
George JM. The synucleins[J]. Genome Biol, 2002, 3(1): REVIEWS3002.
[10]
Maurano MT, Humbert R, Rynes E, et al. Systematic localization of common disease-associated variation in regulatory DNA[J]. Science, 2012, 337(6099): 1190-1195.
[11]
Handel AE, Disanto G, Ramagopalan SV. Next-generation sequencing in understanding complex neurological disease[J]. Expert Rev Neurother, 2013, 13(2): 215-227.
[12]
Foo JN, Liu JJ, Tan EK. Whole-genome and whole-exome sequencing in neurological diseases[J]. Nat Rev Neurol, 2012, 8(9): 508-517.
[13]
Bras J, Guerreiro R, Hardy J. Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease[J]. Nat Rev Neurosci, 2012, 13(7): 453-464.
[14]
Jiang T, Tan MS, Tan L, et al. Application of next-generation sequencing technologies in Neurology[J]. Ann Transl Med, 2014, 2(12): 125.
[15]
Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics[J]. Nat Rev Genet, 2009, 10(1): 57-63.
[16]
Sutherland GT, Janitz M, Kril JJ. Understanding the pathogenesis of Alzheimer’s disease: will RNA-Seq realize the promise of transcriptomics[J]? J Neurochem, 2011, 116(6): 937-946.
[17]
Kukurba KR, Montgomery SB. RNA Sequencing and Analysis[J]. Cold Spring Harb Protoc, 2015, 11: 951-969.
[18]
Malone JH, Oliver B. Microarrays, deep sequencing and the true measure of the transcriptome[J]. BMC Biol, 2011, 9: 34.
[19]
Mortazavi A, Williams BA, McCue K, et al. Mapping and quantifying mammalian transcriptomes by RNA-Seq[J]. Nat Methods, 2008, 5(7): 621-628.
[20]
Nagalakshmi U, Wang Z, Waern K, et al. The transcriptional landscape of the yeast genome defined by RNA sequencing[J]. Science, 2008, 320(5881): 1344-1349.
[21]
Asmann YW, Klee EW, Thompson EA, et al. 3'tag digital gene expression profiling of human brain and universal reference RNA using Illumina Genome Analyzer[J]. BMC Genomics, 2009, 10: 531.
[22]
Wang ET, Sandberg R, Luo S, et al. Alternative isoform regulation in human tissue transcriptomes[J]. Nature, 2008, 456(7221): 470-476.
[23]
Marioni JC, Mason CE, Mane SM, et al. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays[J]. Genome Res, 2008, 18(9): 1509-1517.
[24]
Twine NA, Janitz K, Wilkins MR, et al. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease[J]. PloS One, 2011, 6(1): e16266.
[25]
Mills JD, Nalpathamkalam T, Jacobs HI, et al. RNA-Seq analysis of the parietal cortex in Alzheimer's disease reveals alternatively spliced isoforms related to lipid metabolism[J]. Neurosci Lett, 2013, 536: 90-95.
[26]
Clark MB, Amaral PP, Schlesinger FJ, et al. The reality of pervasive transcription[J]. PloS Biol, 2011, 9(7): e1000625.
[27]
Tokay T, Hachem R, Masmoudi-Kouki O, et al. Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N-formyl peptide receptors[J]. Glia, 2008, 56(13): 1380-1389.
[28]
Satoh J, Yamamoto Y, Asahina N, et al. RNA-Seq data mining: downregulation of NeuroD6 serves as a possible biomarker for alzheimer's disease brains[J]. Dis Markers, 2014: 123165.
[29]
Uittenbogaard M, Chiaramello A. The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators[J]. J Neurochem, 2005, 92(3): 585-596.
[30]
Uittenbogaard M, Baxter KK, Chiaramello A. NeuroD6 genomic signature bridging neuronal differentiation to survival via the molecular chaperone network[J]. J Neurosci Res, 2010, 88(1): 33-54.
[31]
Liew CC, Ma J, Tang HC, et al. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool[J]. J Lab Clin Med, 2006, 147(3): 126-132.
[32]
Cooper-Knock J, Kirby J, Ferraiuolo L, et al. Gene expression profiling in human neurodegenerative disease[J]. Nat Rev Neurol, 2012, 8(9): 518-530.
[33]
Mutez E, Nkiliza A, Belarbi K, et al. Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporic forms of Parkinson's disease[J]. Neurobiol Dis, 2014, 63: 165-170.
[34]
Kannarkat GT, Boss JM, Tansey MG. The role of innate and aptive immunity in Parkinson's disease[J]. J Parkinsons Dis, 2013, 3(4): 493-514.
[35]
Scherzer CR, Eklund AC, Morse LJ, et al. Molecular markers of early Parkinson's disease based on gene expression in blood[J]. Proc Natl Ac Sci USA, 2007, 104(3): 955-960.
[36]
Healy DG, Falchi M, O'Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2 -associated Parkinson's disease: a case-control study[J]. Lancet Neurol, 2008, 7(7): 583-590.
[37]
Infante J, Prieto C, Sierra M, et al. Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2 -G2019S carriers, idiopathic cases, and controls[J]. Neurobiol Aging, 2015, 36(2): 1105-1109.
[38]
Mezey E, Dehejia AM, Harta G, et al. Alpha synuclein is present in Lewy bodies in sporic Parkinson's disease[J]. Mol Psychiatry, 1998, 3(6): 493-499.
[39]
Pankratz N, Beecham GW, Destefano AL, et al. Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2[J]. Journal of Organic Chemistry, 2012, 71(3): 370-384.
[40]
Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease[J]. Science, 1997, 276(5321): 2045-2047.
[41]
Parnetti L, Castrioto A, Chiasserini D, et al. Cerebrospinal fluid biomarkers in Parkinson disease[J]. Nat Rev Neurol, 2013, 9(3): 131-140.
[42]
Hossein-Nezh A, Fatemi RP, Ahm R, et al. Transcriptomic Profiling of Extracellular RNAs present in cerebrospinal fluid identifies differentially expressed transcripts in Parkinson's diseases[J]. J Parkinsons Dis, 2016, 6(1): 109-117.
[43]
Pan Q, Shai O, Lee LJ, et al. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing[J]. Nat Genet, 2008, 40(12): 1413-1415.
[44]
Yeo G, Holste D, Kreiman G, et al. Variation in alternative splicing across human tissues[J]. Genome Biology, 2004, 5(10): R74.
[45]
Faustino NA, Cooper TA. Pre-mRNA splicing and human disease[J]. Genes Dev, 2003, 17(4): 419-437.
[46]
Mills JD, Janitz M. Alternative splicing of mRNA in the molecular pathology of neurodegenerative diseases[J]. Neurobiol Aging, 2012, 33(5): 1012.e11-1012.e24.
[47]
Soreq L, Guffanti A, Salomonis N, et al. Long non-coding RNA and alternative splicing modulations in Parkinson’s leukocytes identified by RNA sequencing[J]. PLoS Comput Biol, 2014, 10(3): e1003517.
[48]
Eddy SR. Non-coding RNA genes and the modern RNA world[J]. Nat Rev Genet, 2001, 2(12): 919-929.
[49]
Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells[J]. Nature, 2012, 489(7414): 101-108.
[50]
Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals[J]. Nature, 2009, 458(7235): 223-227.
[51]
Ulitsky I, Bartel DP. lincRNAs: genomics, fvolution, and mechanisms[J]. Cell, 2013, 154(1): 26-46.
[52]
Carninci P, Kasukawa T, Katayama S, et al. The transcriptional landscape of the mammalian genome[J]. Science, 2005, 309(5740): 1559-1563.
[53]
Ulitsky I, Shkumatava A, Jan CH, et al. Conserved Function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution[J]. Cell, 2011, 147(7): 1537-1550.
[54]
Cabili MN, Trapnell C, Goff L, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses[J]. Genes Dev, 2011, 25(18): 1915-1927.
[55]
Yang L, Lin C, Jin C, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs[J]. Nature, 2013, 500(7464): 598-602.
[56]
Yoon JH, Abdelmohsen K, Gorospe M. Posttranscriptional gene regulation by long noncoding RNA[J]. J Mol Biol, 2013, 425(19): 3723-3730.
[57]
Yoon JH, Abdelmohsen K, Kim J, et al. Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination[J]. Nat Commun, 2013, 4(1): 2939.
[58]
Grammatikakis I, Panda AC, Abdelmohsen K, et al. Long noncoding RNAs（lncRNAs）and the molecular hallmarks of aging[J]. Aging, 2014, 6(12): 992-1009.
[59]
Huarte M, Rinn JL. Large non-coding RNAs: missing links in cancer[J]? Hum Mol Genet, 2010, 19(R2): R152-R161.
[60]
Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view[J]. RNA Biol, 2012, 9(6): 703-719.
[61]
Greco S, Gorospe M, Martelli F. Noncoding RNA in age-related cardiovascular diseases[J]. J Mol Cell Cardiol, 2015, 83: 142-155.
[62]
Qureshi IA, Mattick JS, Mehler MF. Long non-coding RNAs in nervous system function and disease[J]. Brain Res, 2010, 1338: 20-35.
[63]
Qureshi IA, Mehler MF. Non-coding RNA networks underlying cognitive disorders across the lifespan[J]. Trends Mol Med, 2011, 17(6): 337-346.
[64]
Esteller M. Non-coding RNAs in human disease[J]. Nat Rev Genet, 2011, 12(12): 861-874.
[65]
Rinn JL, Chang HY. Genome regulation by long noncoding RNAs[J]. Annu Rev Biochem, 2012, 81: 145-166.
[66]
Wu P, Zuo X, Deng H, et al. Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases[J]. Brain Res Bull, 2013, 97: 69-80.
[67]
Roberts TC, Morris KV, Wood MJ. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease[J]. Philos Trans R Soc Lond B Biol Sci, 2014, 369(1652). doi: 10.1098/rstb.2013.0507.
[68]
Ng SY, Lin L, Soh BS, et al. Long noncoding RNAs in development and disease of the central nervous system[J]. Trends in Genetics Tig, 2013, 29(8): 461-468.
[69]
Magistri M, Velmeshev D, Makhmutova M, et al. Transcriptomics profiling of Alzheimer’s disease reveal neurovascular defects, altered amyloid-βhomeostasis, and deregulated expression of long noncoding RNAs[J]. J Alzheimers Dis, 2015, 48(3): 647-665.
[70]
Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells[J]. Cancer Res, 2005, 65(14): 6029-6033.
[71]
Kim J, Inoue K, Ishii J, et al. A MicroRNA feedback circuit inmidbrain dopamine neurons[J]. Science, 2007, 317(5842): 1220-1224.
[72]
O'Carroll D, Schaefer A. General principals of miRNA biogenesis and regulation in the brain[J]. Neuropsychopharmacology, 2013, 38(1): 39-54.
[73]
Nelson PT, Wang WX, Rajeev BW. MicroRNAs(miRNAs) in neurodegenerative diseases[J]. Brain Pathol, 2008, 18(1): 130-138.
[74]
Leidinger P, Backes C, Deutscher S, et al. A blood based 12-miRNA signature of Alzheimer disease patients[J]. Genome Biol, 2013, 14(7): R78.
[75]
Keller A, Backes C, Haas J, et al. Validating Alzheimer's disease micro RNAs using next-generation sequencing[J]. Alzheimer's Dementia, 2016, 12(5): 565-576.
[76]
Dong H, Li J, Huang L, et al. Serum microRNA profiles serve as novel biomarkers for the diagnosis of Alzheimer's disease[J]. Dis Markers, 2015: 625659.
[77]
Ding H, Huang Z, Chen M, et al. Identification of a panel of five serum miRNAs as a biomarker for Parkinson's disease[J]. Parkinsonism Relat Disord, 2016, 22: 68-73.
[78]
Dong H, Wang C, Lu S, et al. A panel of four decreased serum microRNAs as a novel biomarker for early Parkinson's disease[J]. Biomarkers, 2016, 21(2): 129-137.
[79]
Lugli G, Cohen AM, Bennett DA, et al. Plasma exosomal miRNAs in persons with and without Alzheimer disease: altered expression and prospects for biomarkers[J]. PloS One, 2015, 10(10): e0139233.
[80]
Hébert SS, Wang WX, Zhu Q, et al. A study of small RNAs from cerebral neocortex of pathology-verified Alzheimer's disease, dementia with lewy bodies, hippocampal sclerosis, frontotemporal lobar dementia, and non-demented human controls[J]. J of Alzheimers Dis, 2013, 35(2): 335-348.
[81]
Burgos K, Malenica I, Metpally R, et al. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology[J]. PloS One, 2014, 9(5): e94839.
[82]
Hoss AG, Laborf A, Beach TG, et al. microRNA profiles in Parkinson's disease prefrontal cortex[J].Front Aging Neurosci, 2016, 8: 36.
[83]
Kong Y, Liang X, Liu L, et al. High throughput sequencing identifies microRNAs mediatingα-synuclein toxicity by targeting neuroactive-ligand receptor interaction pathway in early stage of drosophila Parkinson's disease model[J]. PloS One, 2015, 10(9): e0137432.
[84]
Atz M, Walsh D, Cartagena P, et al. Methodological considerations for gene expression profiling of human brain[J]. J Neurosci Methods, 2007, 163(2): 295-309.
[85]
Monoranu CM, Apfelbacher M, Grünblatt E, et al. pH measurement as quality control on human post mortem brain tissue: a study of the BrainNet Europe consortium[J]. Neuropathol Appl Neurobiol, 2009, 35(3): 329-337.
[86]
Rueter SM, Dawson TR, Emeson RB. Regulation of alternative splicing by RNA editing[J]. Nature, 1999, 399(6731):75-80.
[87]
Bass BL. RNA editing by enosine deaminases that act on RNA[J]. Annu Rev Biochem, 2002, 71: 817-846.
[88]
Levanon EY, Eisenberg E, Yelin R, et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome[J]. Nat Biotechnol, 2004, 22(8): 1001-1005.
[89]
Blow MJ, Grocock RJ, Dongen SV, et al. RNA editing of human microRNAs[J]. Genome Biol, 2006, 7(4): R27.
[90]
Li JB, Church GM. Deciphering the functions and regulation of brain-enriched A-to-I RNA editing[J]. Nat Neurosci, 2013, 16(11): 1518-1522.
[91]
Singh M. Dysregulated A to I RNA editing and non-coding RNAs in neurodegeneration[J]. Front Genet, 2013, 3: 326.
[92]
Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges[J]. Nature, 2013, 495(7441): 384-388.
[93]
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency[J]. Nature, 2013, 495(7441): 333-338.
[94]
VenøMT, Hansen TB, VenøST, et al. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development[J]. Genome Biol, 2015, 16: 245.
[95]
Lukiw WJ. Circular RNA(circRNA) in Alzheimer's disease[J]. Front in Genet, 2013, 4: 307.
[96]
Lu D, Xu A-D. Mini review: circular rnas as potential clinical biomarkers for disorders in the central nervous system[J]. Front Genet, 2016, 7: 53.
[97]
Liu S, Trapnell C. Single-cell transcriptome sequencing: recent vances and remaining challenges[J]. F1000Res, 2016, 5. doi: 10.12688/f1000research.7223.1.
[98]
Macaulay IC, Voet T. Single cell genomics: vances and future perspectives[J]. PloS Genet, 2014, 10(1): e1004126.
[99]
Rhos A, Au KF. PacBio sequencing and its applications[J]. Genomics Proteomics Bioinformatics, 2015, 13(5): 278-289.
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