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Applications of Second Generation Sequencing Technologies in Complex Disorders

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Behavioral Neurogenetics

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 12))

Abstract

Second generation sequencing (2ndGS) technologies generate unprecedented amounts of sequence data very rapidly and at relatively limited costs, allowing the sequence of a human genome to be completed in a few weeks. The principle is on the basis of generating millions of relatively short reads from amplified single DNA fragments using iterative cycles of nucleotide extensions. However, the data generated on this scale present new challenges in interpretation, data analysis and data management. 2ndGS technologies are becoming widespread and are profoundly impacting biomedical research. Common applications include whole-genome sequencing, target resequencing, characterization of structural and copy number variation, profiling epigenetic modifications, transcriptome sequencing and identification of infectious agents. New methodologies and instruments that will enable to sequence the complete human genome in less than a day at a cost of less than $1,000 are currently in development.

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References

  • Ansorge WJ (2009) Next-generation DNA sequencing techniques. N Biotechnol 25(4):195–203

    Article  PubMed  CAS  Google Scholar 

  • Bentley DR, Balasubramanian S, Swerdlow HP et al (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59

    Article  PubMed  CAS  Google Scholar 

  • Brkanac Z, Spencer D, Shendure J et al (2009) IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23. Am J Hum Genet 84(5):692–697

    Article  PubMed  CAS  Google Scholar 

  • Bryant DW Jr, Shen R, Priest HD, Wong WK, Mockler TC (2010) Supersplat–spliced RNA-seq alignment. Bioinformatics 26(12):1500–1505

    Article  PubMed  CAS  Google Scholar 

  • Cirulli ET, Singh A, Shianna KV et al (2010) Screening the human exome: a comparison of whole genome and whole transcriptome sequencing. Genome Biol 11(5):R57

    PubMed  Google Scholar 

  • Chen W, Kalscheuer V, Tzschach A et al (2008) Mapping translocation breakpoints by next-generation sequencing. Genome Res 18(7):1143–1149

    Article  PubMed  CAS  Google Scholar 

  • Dames S, Durtschi J, Geiersbach K, Stephens J, Voelkerding KV (2010) Comparison of the Illumina genome analyzer and roche 454 GS FLX for resequencing of hypertrophic cardiomyopathy-associated genes. J Biomol Tech 21(2):73–80

    PubMed  Google Scholar 

  • Diehl F, Li M, He Y, Kinzler KW, Vogelstein B, Dressman D (2006) BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods 3(7):551–559

    Article  PubMed  CAS  Google Scholar 

  • Ding L, Ellis MJ, Li S, Larson DE et al (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464(7291):999–1005

    Article  PubMed  CAS  Google Scholar 

  • Feng H, Shuda M, Chang Y, Moore PS (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann C, Minkah N, Leipzig J et al (2007) DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations. Nucleic Acids Res 35(13):e91

    Article  PubMed  Google Scholar 

  • Holt RA, Jones SJ (2008) The new paradigm of flow cell sequencing. Genome Res 18(6):839–846

    Article  PubMed  CAS  Google Scholar 

  • Jones S, Hruban RH, Kamiyama M et al (2009) Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324(5924):217

    Article  PubMed  CAS  Google Scholar 

  • Koboldt DC, Chen K, Wylie T et al (2009) VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 25(17):2283–2285

    Article  PubMed  CAS  Google Scholar 

  • Koboldt DC, Ding L, Mardis ER, Wilson RK (2010) Challenges of sequencing human genomes. Brief Bioinform 11(5):484–498

    Article  PubMed  CAS  Google Scholar 

  • Korlach J, Bjornson KP, Chaudhuri BP et al (2010) Real-time DNA sequencing from single polymerase molecules. Methods Enzymol 472:431–455

    Article  PubMed  CAS  Google Scholar 

  • Ku CS, Loy EY, Salim A, Pawitan Y, Chia KS (2010) The discovery of human genetic variations and their use as disease markers: past, present and future. J Hum Genet 55(7):403–415

    Article  PubMed  Google Scholar 

  • Li H, Handsaker B, Wysoker A et al (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25(16):2078–2079

    Article  PubMed  Google Scholar 

  • Li H, Homer N (2010) A survey of sequence alignment algorithms for next-generation sequencing. Brief Bioinform 11(5):473–483

    Article  PubMed  CAS  Google Scholar 

  • Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    Article  PubMed  CAS  Google Scholar 

  • Lister R, Ecker JR (2009) Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res 19(6):959–966

    Article  PubMed  CAS  Google Scholar 

  • Lister R, Pelizzola M, Dowen RH et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322

    Article  PubMed  CAS  Google Scholar 

  • Lupski JR, Reid JG, Gonzaga-Jauregui C et al (2010) Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med 362(13):1181–1191

    Article  PubMed  CAS  Google Scholar 

  • MacLean D, Jones JD, Studholme DJ (2009) Application of ‘next-generation’ sequencing technologies to microbial genetics. Nat Rev Microbiol 7(4):287–296

    PubMed  Google Scholar 

  • Maher CA, Palanisamy N, Brenner JC et al (2009) Chimeric transcript discovery by paired-end transcriptome sequencing. Proc Natl Acad Sci U S A 106(30):12353–12358

    Article  PubMed  CAS  Google Scholar 

  • Mamanova L, Coffey AJ, Scott CE et al (2010) Target-enrichment strategies for next-generation sequencing. Nat Methods 7(2):111–118

    Article  PubMed  CAS  Google Scholar 

  • Mardis ER (2009) New strategies and emerging technologies for massively parallel sequencing: applications in medical research. Genome Med 1(4):40

    Article  PubMed  Google Scholar 

  • Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380

    PubMed  CAS  Google Scholar 

  • Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci 74(2):560–564

    Article  PubMed  CAS  Google Scholar 

  • Medvedev P, Stanciu M, Brudno M (2009) Computational methods for discovering structural variation with next-generation sequencing. Nat Methods 6(11 Suppl):S13–S20

    Article  PubMed  CAS  Google Scholar 

  • McCarthy MI (2009) Exploring the unknown: assumptions about allelic architecture and strategies for susceptibility variant discovery. Genome Med 1(7):66

    Article  PubMed  Google Scholar 

  • Morgan JE, Carr IM, Sheridan E et al (2010) Genetic diagnosis of familial breast cancer using clonal sequencing. Hum Mutat 31(4):484–491

    Article  PubMed  CAS  Google Scholar 

  • Morozova O, Hirst M, Marra MA (2009) Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet 10:135–151

    Article  PubMed  CAS  Google Scholar 

  • Ng SB, Buckingham KJ, Lee C et al (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30–35

    Article  PubMed  CAS  Google Scholar 

  • Nikopoulos K, Gilissen C, Hoischen A et al (2010) Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretinopathy. Am J Hum Genet 86(2):240–247

    Article  PubMed  CAS  Google Scholar 

  • Nygaard S, Jacobsen A, Lindow M et al (2009) Identification and analysis of miRNAs in human breast cancer and teratoma samples using deep sequencing. BMC Med Genomics 2:35

    PubMed  Google Scholar 

  • Palacios G, Druce J, Du L et al (2008) A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 358(10):991–998

    Article  PubMed  CAS  Google Scholar 

  • Park PJ (2008) Epigenetics meets next-generation sequencing. Epigenetics 3(6):318–321

    Article  PubMed  Google Scholar 

  • Robison K (2010) Application of second-generation sequencing to cancer genomics. Brief Bioinform 11:524–534 (Epub ahead of print)

    Google Scholar 

  • Ronaghi M, Karamohamed S, Pettersson B et al (1996) Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 242:84–89

    Article  PubMed  CAS  Google Scholar 

  • Sanger F, Nicklen S, Coulson AR (1977) DNA Sequencing with chain-terminating inhibitors. Proc Natl Acad Sci 74:546–567

    Article  Google Scholar 

  • Schadt EE, Turner S, Kasarskis A (2010) A window into third-generation sequencing. Hum Mol Genet 19(R2):R227–R240

    Article  PubMed  CAS  Google Scholar 

  • Shah SP, Köbel M, Senz J et al (2009) Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 360(26):2719–2729

    Article  PubMed  CAS  Google Scholar 

  • Sobreira NL, Cirulli ET, Avramopoulos D et al (2010) Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet 6(6):e1000991

    Article  PubMed  Google Scholar 

  • Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458(7239):719–724

    Article  PubMed  CAS  Google Scholar 

  • Tang F, Barbacioru C, Nordman E et al (2010) RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protoc 5(3):516–535

    Article  PubMed  CAS  Google Scholar 

  • The international cancer genome consortium. Hudson TJ, Anderson W, Artez A et al (2010) International network of cancer genome projects. Nature 464(7291):993–998

    Article  Google Scholar 

  • Trapnell C, Pachter L, Salzberg SL (2009) Tophat: discovering splice junctions with RNA-Seq. Bioinformatics 25(9):1105–1111

    Article  PubMed  CAS  Google Scholar 

  • Uziel T, Karginov FV, Xie S et al (2009) The MIR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A 106(8):2812–2817

    Article  PubMed  CAS  Google Scholar 

  • Vasta V, Ng SB, Turner EH, Shendure J, Hahn SH (2009) Next generation sequence analysis for mitochondrial disorders. Genome Med 1(10):100

    Article  PubMed  Google Scholar 

  • Venter JC, Adams MD, Myers EW et al (2001) The sequence of the human genome. Science 291(5507):1304–1351

    Article  PubMed  CAS  Google Scholar 

  • Voelkerding KV, Dames SA, Durtschi JD (2009) Next-generation sequencing: from basic research to diagnostics. Clin Chem 55(4):641–658

    Article  PubMed  CAS  Google Scholar 

  • Volpi L, Roversi G, Colombo EA et al (2010) Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet 86(1):72–76

    Article  PubMed  CAS  Google Scholar 

  • Walsh T, Lee MK, Casadei S et al (2010) Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci 107(28):12629–12633

    Article  PubMed  CAS  Google Scholar 

  • Weise A, Timmermann B, Grabherr M et al (2010) High-throughput sequencing of microdissected chromosomal regions. Eur J Hum Genet 18(4):457–462

    Article  PubMed  Google Scholar 

  • Wyman SK, Parkin RK, Mitchell PS et al (2009) Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One 4(4):e5311

    Article  PubMed  Google Scholar 

  • Yeager M, Xiao N, Hayes RB et al (2008) Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers. Hum Genet 124(2):161–170

    Article  PubMed  CAS  Google Scholar 

  • Zhao Q, Caballero OL, Levy S et al (2009) Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line. Proc Natl Acad Sci U S A 106(6):1886–1891

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Mònica Bayés .

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Bayés, M., Heath, S., Gut, I.G. (2011). Applications of Second Generation Sequencing Technologies in Complex Disorders. In: Cryan, J., Reif, A. (eds) Behavioral Neurogenetics. Current Topics in Behavioral Neurosciences, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_196

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