Skip to main content
SpringerLink
Log in
Book cover

Chemical Diagnostics pp 19–45Cite as

Application of Next Generation Sequencing to Molecular Diagnosis of Inherited Diseases

  • Chapter
  • First Online:

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 336))

Abstract

Recent development of high throughput, massively parallel sequencing (MPS or next generation sequencing, NGS) technology has revolutionized the molecular diagnosis of human genetic disease. The ability to generate enormous amount of sequence data in a short time at an affordable cost makes this approach ideal for a wide range of applications from sequencing a group of candidate genes, all coding regions (known as exome sequencing) to the entire human genome. The technology brings about an unprecedented application to the identification of the molecular basis of hard-to-diagnose genetic disorders. This chapter reviews the up-to-date published application of next generation sequencing in clinical molecular diagnostic laboratories. We also emphasize the various target gene enrichment methods and their advantages and shortcomings. Obstacles to compliance with regulatory authorities like CLIA/CAP in clinical settings are also briefly discussed.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74(12):5463–5467

    CAS  Google Scholar 

  2. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong S-E et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112–123

    CAS  Google Scholar 

  3. Calvo S, Jain M, Xie X, Sheth SA, Chang B, Goldberger OA et al (2006) Systematic identification of human mitochondrial disease genes through integrative genomics. Nat Genet 38(5):576–582

    CAS  Google Scholar 

  4. Thorburn D (2004) Mitochondrial disorders: prevalence, myths and advances. J Inherit Metab Dis 27(3):349–362

    CAS  Google Scholar 

  5. Scharfe C, Lu HH-S, Neuenburg JK, Allen EA, Li G-C, Klopstock T et al (2009) Mapping gene associations in human mitochondria using clinical disease phenotypes. PLoS Comput Biol 5(4):e1000374

    Google Scholar 

  6. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP et al (2007) The diploid genome sequence of an individual human. PLoS Biol 5(10):e254

    Google Scholar 

  7. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A et al (2008) The complete genome of an individual by massively parallel DNA sequencing. Nature 452(7189):872–876

    CAS  Google Scholar 

  8. Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE, Dewey FE et al (2010) Clinical assessment incorporating a personal genome. Lancet 375(9725):1525–1535

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  10. Dewey FE, Chen R, Cordero SP, Ormond KE, Caleshu C, Karczewski KJ et al (2011) Phased whole-genome genetic risk in a family quartet using a major allele reference sequence. PLoS Genet 7(9):e1002280

    CAS  Google Scholar 

  11. Bainbridge MN, Wiszniewski W, Murdock DR, Friedman J, Gonzaga-Jauregui C, Newsham I et al (2011) Whole-genome sequencing for optimized patient management. Sci Transl Med 3(87):87re3

    Google Scholar 

  12. 1000 Genomes Project Consortium (2010) A map of human genome variation from population-scale sequencing. Nature 467(7319):1061–1073

    Google Scholar 

  13. Mardis ER (2008) Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet 9(1):387–402

    CAS  Google Scholar 

  14. Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11(1):31–46

    CAS  Google Scholar 

  15. Shendure J, Ji H (2008) Next-generation DNA sequencing. Nat Biotechnol 26(10):1135–1145

    CAS  Google Scholar 

  16. Gibbs RA (2011) Bringing genomics and genetics back together. Science 331(6017):548

    Google Scholar 

  17. Collins FS (2011) Faces of the genome. Science 331(6017):546

    Google Scholar 

  18. Green ED, Guyer MS (2011) Charting a course for genomic medicine from base pairs to bedside. Nature 470(7333):204–213

    CAS  Google Scholar 

  19. Lander ES (2011) Initial impact of the sequencing of the human genome. Nature 470(7333):187–197

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  21. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380

    CAS  Google Scholar 

  22. Bennett S (2004) Solexa Ltd. Pharmacogenomics 5(4):433–438

    Google Scholar 

  23. Bennett ST, Barnes C, Cox A, Davies L, Brown C (2005) Toward the $1000 human genome. Pharmacogenomics 6(4):373–382

    CAS  Google Scholar 

  24. Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM et al (2005) Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309(5741):1728–1732

    CAS  Google Scholar 

  25. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M et al (2011) An integrated semiconductor device enabling non-optical genome sequencing. Nature 475(7356):348–352

    CAS  Google Scholar 

  26. Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Braslavsky I et al (2008) Single-molecule DNA sequencing of a viral genome. Science 320(5872):106–109

    CAS  Google Scholar 

  27. Korlach J, Bjornson KP, Chaudhuri BP, Cicero RL, Flusberg BA, Gray JJ et al (2010) Chapter 20: Real-time DNA sequencing from single polymerase molecules. Methods in Enzymology. Academic, pp 431–455

    Google Scholar 

  28. Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA et al (2010) Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods 7(6):461–465

    CAS  Google Scholar 

  29. Turner EH, Ng SB, Nickerson DA, Shendure J (2009) Methods for genomic partitioning. Annu Rev Genomics Hum Genet 10(1):263–284

    CAS  Google Scholar 

  30. Ng SB, Nickerson DA, Bamshad MJ, Shendure J (2010) Massively parallel sequencing and rare disease. Hum Mol Genet 19(R2):R119–R124

    CAS  Google Scholar 

  31. Lu C, Tej SS, Luo S, Haudenschild CD, Meyers BC, Green PJ (2005) Elucidation of the small RNA component of the transcriptome. Science 309(5740):1567–1569

    CAS  Google Scholar 

  32. Axtell MJ, Jan C, Rajagopalan R, Bartel DP (2006) A two-hit trigger for siRNA biogenesis in plants. Cell 127(3):565–577

    CAS  Google Scholar 

  33. Morin RD, O'Connor MD, Griffith M, Kuchenbauer F, Delaney A, Prabhu A-L et al (2008) Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res 18(4):610–621

    CAS  Google Scholar 

  34. Martin JA, Wang Z (2011) Next-generation transcriptome assembly. Nat Rev Genet 12(10):671–682

    CAS  Google Scholar 

  35. Hawkins RD, Hon GC, Ren B (2010) Next-generation genomics: an integrative approach. Nat Rev Genet 11(7):476–486

    CAS  Google Scholar 

  36. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322

    CAS  Google Scholar 

  37. Hu H, Wrogemann K, Kalscheuer V, Tzschach A, Richard H, Haas SA et al (2009) Mutation screening in 86 known X-linked mental retardation genes by droplet-based multiplex PCR and massive parallel sequencing. Hugo J 3(1–4):41–49

    CAS  Google Scholar 

  38. Gowrisankar S, Lerner-Ellis JP, Cox S, White ET, Manion M, LeVan K et al (2010) Evaluation of second-generation sequencing of 19 dilated cardiomyopathy genes for clinical applications. J Mol Diagn 12(6):818–827

    CAS  Google Scholar 

  39. Voelkerding KV, Dames S, Durtschi JD (2010) Next generation sequencing for clinical diagnostics-principles and application to targeted resequencing for hypertrophic cardiomyopathy: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diagn 12(5):539–551

    Google Scholar 

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

    Google Scholar 

  41. Lubin IM, Caggana M, Constantin C, Gross SJ, Lyon E, Pagon RA et al (2008) Ordering molecular genetic tests and reporting results: practices in laboratory and clinical settings. J Mol Diagn 10(5):459–468

    Google Scholar 

  42. Maddalena A, Bale S, Das S, Grody W, Richards S, the ALQAC (2005) Technical standards and guidelines: molecular genetic testing for ultra-rare disorders. Genet Med 7(8):571–583

    Google Scholar 

  43. Chen B, Gagnon M, Shahangian S, Anderson NL, Howerton DA, Boone JD (2009) Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR Recomm Rep 58(RR-6):1–37, quiz CE-1-4

    Google Scholar 

  44. Vance GH (2011) College of American pathologists proposal for the oversight of laboratory-developed tests. Arch Pathol Lab Med 135(11):1432–1435

    Google Scholar 

  45. Chou L-S, Liu CSJ, Boese B, Zhang X, Mao R (2010) DNA sequence capture and enrichment by microarray followed by next-generation sequencing for targeted resequencing: neurofibromatosis type 1 gene as a model. Clin Chem 56(1):62–72

    CAS  Google Scholar 

  46. Baetens M, Van Laer L, De Leeneer K, Hellemans J, De Schrijver J, Van De Voorde H et al (2011) Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes. Hum Mutat 32(9):1053–1062

    CAS  Google Scholar 

  47. Schlipf NA, Schüle R, Klimpe S, Karle KN, Synofzik M, Schicks J et al (2011) Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clin Genet 80(2):148–160

    CAS  Google Scholar 

  48. Jones MA, Bhide S, Chin E, Ng BG, Rhodenizer D, Zhang VW et al (2011) Targeted polymerase chain reaction-based enrichment and next generation sequencing for diagnostic testing of congenital disorders of glycosylation. Genet Med 13(11):921–932

    CAS  Google Scholar 

  49. Simpson DA, Clark GR, Alexander S, Silvestri G, Willoughby CE (2011) Molecular diagnosis for heterogeneous genetic diseases with targeted high-throughput DNA sequencing applied to retinitis pigmentosa. J Med Genet 48(3):145–151

    Google Scholar 

  50. Tang S, Huang T (2010) Characterization of mitochondrial DNA heteroplasmy using a parallel sequencing system. Biotechniques 48(4):287–296

    CAS  Google Scholar 

  51. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J et al (2011) Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 3(65):65ra4

    CAS  Google Scholar 

  52. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM et al (2009) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30–35

    Google Scholar 

  53. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI et al (2010) Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 42(9):790–793

    CAS  Google Scholar 

  54. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B et al (2011) Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 13(3):255–262

    Google Scholar 

  55. Chiu RWK, Sun H, Akolekar R, Clouser C, Lee C, McKernan K et al (2010) Maternal plasma DNA analysis with massively parallel sequencing by ligation for noninvasive prenatal diagnosis of trisomy 21. Clin Chem 56(3):459–463

    CAS  Google Scholar 

  56. Rasmussen SA, Friedman JM (2000) NF1 gene and neurofibromatosis 1. Am J Epidemiol 151(1):33–40

    CAS  Google Scholar 

  57. Messiaen LM, Callens T, Mortier G, Beysen D, Vandenbroucke I, Van Roy N et al (2000) Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat 15(6):541–555

    CAS  Google Scholar 

  58. Judge DP, Dietz HC (2005) Marfan’s syndrome. Lancet 366(9501):1965–1976

    CAS  Google Scholar 

  59. Robinson PN, Arteaga-Solis E, Baldock C, Collod-Baroud G, Booms P, De Paepe A et al (2006) The molecular genetics of Marfan syndrome and related disorders. J Med Genet 43(10):769–787

    CAS  Google Scholar 

  60. Salinas S, Proukakis C, Crosby A, Warner TT (2008) Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol 7(12):1127–1138

    CAS  Google Scholar 

  61. Zimmerman RS, Cox S, Lakdawala NK, Cirino A, Mancini-DiNardo D, Clark E et al (2010) A novel custom resequencing array for dilated cardiomyopathy. Genet Med 12(5):268–278. doi:10.1097/GIM.0b013e3181d6f7c0

    Google Scholar 

  62. Sakai H, Suzuki S, Mizuguchi T, Imoto K, Yamashita Y, Doi H et al (2012) Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods: resequencing microarray technology and next-generation sequencing. Hum Genet 131(4):591–599

    CAS  Google Scholar 

  63. Jaeken J, Matthijs G (2007) Congenital disorders of glycosylation: a rapidly expanding disease family. Annu Rev Genomics Hum Genet 8(1):261–278

    CAS  Google Scholar 

  64. Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL et al (2010) SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell 142(2):203–217

    CAS  Google Scholar 

  65. Ng BG, Sharma V, Sun L, Loh E, Hong W, Tay SKH et al (2011) Identification of the first COG-CDG patient of Indian origin. Mol Genet Metab 102(3):364–367

    CAS  Google Scholar 

  66. Matthijs G, Schollen E, Bjursell C, Erlandson A, Freeze H, Imtiaz F et al (2000) Mutations in PMM2 that cause congenital disorders of glycosylation, type Ia (CDG-Ia). Hum Mutat 16(5):386–394

    CAS  Google Scholar 

  67. Fishman GA (1978) Retinitis pigmentosa: visual loss. Arch Ophthalmol 96(7):1185–1188

    CAS  Google Scholar 

  68. Ropers HH (2008) Genetics of intellectual disability. Curr Opin Genet Dev 18(3):241–250

    CAS  Google Scholar 

  69. Wong L-JC (2010) Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev 16(2):154–162

    Google Scholar 

  70. Huang T (2010) Next generation sequencing to characterize mitochondrial genomic DNA heteroplasmy. Current Protocols in Human Genetics. Wiley

    Google Scholar 

  71. Cui H, Zhang W, Wong L-JC (2011) Comprehensive molecular analyses of mitochondrial genome by next-generation sequencing 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; 2011; Montreal, Canada, 2011

    Google Scholar 

  72. Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N et al (2008) The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab 94(1):16–37

    CAS  Google Scholar 

  73. Wong L-JC, Scaglia F, Graham BH, Craigen WJ (2010) Current molecular diagnostic algorithm for mitochondrial disorders. Mol Genet Metab 100(2):111–117

    CAS  Google Scholar 

  74. Berardo A, DiMauro S, Hirano M (2010) A diagnostic algorithm for metabolic myopathies. Curr Neurol Neurosci Rep 10(2):118–126

    CAS  Google Scholar 

  75. DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Annu Rev Neurosci 31(1):91–123

    CAS  Google Scholar 

  76. Costa T, Scriver CR, Childs B (1985) The effect of Mendelian disease on human health: a measurement. Am J Med Genet 21(2):231–242

    CAS  Google Scholar 

  77. Kumar P, Radhakrishnan J, Chowdhary MA, Giampietro PF (2001) Prevalence and patterns of presentation of genetic disorders in a pediatric emergency department. Mayo Clin Proc 76(8):777–783

    CAS  Google Scholar 

  78. Boone P, Wiszniewski W, Lupski J (2011) Genomic medicine and neurological disease. Hum Genet 130(1):103–121

    CAS  Google Scholar 

  79. Biesecker LG (2010) Exome sequencing makes medical genomics a reality. Nat Genet 42(1):13–14

    CAS  Google Scholar 

  80. Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CWG et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076):485–487

    CAS  Google Scholar 

  81. Rossa WKC, Ranjit A, Yama WLZ, Tak YL, Hao S, Chan KCA et al (2011) Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 342:c7401

    Google Scholar 

  82. Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R et al (2011) Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 204(3):205.e1–e11

    Google Scholar 

  83. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M et al (2011) DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 13(11):913–920

    CAS  Google Scholar 

  84. Lo YMD, Chan KCA, Sun H, Chen EZ, Jiang P, Lun FMF et al (2010) Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2(61):61ra91

    CAS  Google Scholar 

  85. Ottesen EA, Hong JW, Quake SR, Leadbetter JR (2006) Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Science 314(5804):1464–1467

    CAS  Google Scholar 

  86. Spurgeon SL, Jones RC, Ramakrishnan R (2008) High throughput gene expression measurement with real time PCR in a microfluidic dynamic array. PLoS One 3(2):e1662

    Google Scholar 

  87. Tewhey R, Warner JB, Nakano M, Libby B, Medkova M, David PH et al (2009) Microdroplet-based PCR enrichment for large-scale targeted sequencing. Nat Biotechnol 27(11):1025–1031

    CAS  Google Scholar 

  88. Okou DT, Steinberg KM, Middle C, Cutler DJ, Albert TJ, Zwick ME (2007) Microarray-based genomic selection for high-throughput resequencing. Nat Methods 4(11):907–909

    CAS  Google Scholar 

  89. Okou DT, Locke AE, Steinberg KM, Hagen K, Athri P, Shetty AC et al (2009) Combining microarray-based genomic selection (MGS) with the illumina genome analyzer platform to sequence diploid target regions. Ann Hum Genet 73(5):502–513

    CAS  Google Scholar 

  90. Clark MJ, Chen R, Lam HYK, Karczewski KJ, Chen R, Euskirchen G et al (2011) Performance comparison of exome DNA sequencing technologies. Nat Biotechnol 29(10):908–914

    CAS  Google Scholar 

  91. Sulonen A-M, Ellonen P, Almusa H, Lepisto M, Eldfors S, Hannula S et al (2011) Comparison of solution-based exome capture methods for next generation sequencing. Genome Biol 12(9):R94

    CAS  Google Scholar 

  92. Asan, Xu Y, Jiang H, Tyler-Smith C, Xue Y, Jiang T et al (2011) Comprehensive comparison of three commercial human whole-exome capture platforms. Genome Biol 12(9):R95

    CAS  Google Scholar 

  93. Parla J, Iossifov I, Grabill I, Spector M, Kramer M, McCombie WR (2011) A comparative analysis of exome capture. Genome Biol 12(9):R97

    CAS  Google Scholar 

  94. Robinson PN, Krawitz P, Mundlos S (2011) Strategies for exome and genome sequence data analysis in disease-gene discovery projects. Clin Genet 80(2):127–132

    Google Scholar 

  95. Tucker EJ, Mimaki M, Compton AG, McKenzie M, Ryan MT, Thorburn DR (2012) Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. Hum Mutat 33(2):411–418

    CAS  Google Scholar 

  96. De Leeneer K, De Schrijver J, Clement L, Baetens M, Lefever S, De Keulenaer S et al (2011) Practical tools to implement massive parallel pyrosequencing of PCR products in next generation molecular diagnostics. PLoS One 6(9):e25531

    Google Scholar 

  97. The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449(7164):851–861

    Google Scholar 

  98. Vissers LELM, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P et al (2010) A de novo paradigm for mental retardation. Nat Genet 42(12):1109–1112

    CAS  Google Scholar 

  99. O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S et al (2011) Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet 43(6):585–589

    Google Scholar 

  100. Lindblom A, Robinson PN (2011) Bioinformatics for human genetics: promises and challenges. Hum Mutat 32(5):495–500

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  102. Wei Q, Wang L, Wang Q, Kruger WD, Dunbrack RL (2010) Testing computational prediction of missense mutation phenotypes: Functional characterization of 204 mutations of human cystathionine beta synthase. Proteins 78(9):2058–2074

    CAS  Google Scholar 

  103. Roach JC, Glusman G, Smit AFA, Huff CD, Hubley R, Shannon PT et al (2010) Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328(5978):636–639

    CAS  Google Scholar 

  104. Robinson P (2010) Whole-exome sequencing for finding de novo mutations in sporadic mental retardation. Genome Biol 11(12):144

    Google Scholar 

  105. Ross JS (2011) Next-generation pathology. Am J Clin Pathol 135(5):663–665

    Google Scholar 

  106. Lucy Raymond F, Whittaker J, Jenkins L, Lench N, Chitty LS (2010) Molecular prenatal diagnosis: the impact of modern technologies. Prenat Diagn 30(7):674–681

    Google Scholar 

  107. Robin NH (2011) Dysmorphology in the era of whole exome sequencing. Curr Opin Pediatr 23(6):579–580

    Google Scholar 

  108. Yngvadottir B, MacArthur D, Jin H, Tyler-Smith C (2009) The promise and reality of personal genomics. Genome Biol 10(9):237

    Google Scholar 

  109. Lam HYK, Clark MJ, Chen R, Chen R, Natsoulis G, O'Huallachain M et al (2011) Performance comparison of whole-genome sequencing platforms. Nat Biotechnol 30(1):78–82

    Google Scholar 

  110. Greenberg CR, Dilling LA, Thompson GR, Seargeant LE, Haworth JC, Phillips S et al (2009) The paradox of the carnitine palmitoyltransferase type Ia P479L variant in Canadian Aboriginal populations. Mol Genet Metab 96(4):201–207

    CAS  Google Scholar 

  111. Collins SA, Sinclair G, McIntosh S, Bamforth F, Thompson R, Sobol I et al (2010) Carnitine palmitoyltransferase 1A (CPT1A) P479L prevalence in live newborns in Yukon, Northwest Territories, and Nunavut. Mol Genet Metab 101(2–3):200–204

    CAS  Google Scholar 

  112. Bick D, Dimmock D (2011) Whole exome and whole genome sequencing. Curr Opin Pediatr 23(6):594–600

    Google Scholar 

  113. Mayer AN, Dimmock DP, Arca MJ, Bick DP, Verbsky JW, Worthey EA et al (2011) A timely arrival for genomic medicine. Genet Med 13(3):195–196

    Google Scholar 

  114. Andrew BS (2011) Exome sequencing: a transformative technology. Lancet Neurol 10(10):942–946

    Google Scholar 

  115. Teer JK, Mullikin JC (2010) Exome sequencing: the sweet spot before whole genomes. Hum Mol Genet 19(R2):R145–R151

    CAS  Google Scholar 

  116. Jackson L, Pyeritz RE (2011) Molecular technologies open new clinical genetic vistas. Sci Transl Med 3(65):65ps2

    Google Scholar 

Download references

Acknowledgement

This work is partially supported by a grant from Muscular Dystrophy Association (Research #175369) to Dr. Lee-Jun Wong.

Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX, 77030, USA

    Wei Zhang, Hong Cui & Lee-Jun C. Wong

Authors
  1. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lee-Jun C. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lee-Jun C. Wong .

Editor information

Editors and Affiliations

  1. Dept. of Chemical Pathology and Lab. of Genetics of Disease Suscept., The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Nelson L.S. Tang

  2. Department of Paediatrics and Proteomics Laboratory, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Terence Poon

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Zhang, W., Cui, H., Wong, LJ.C. (2012). Application of Next Generation Sequencing to Molecular Diagnosis of Inherited Diseases. In: L.S. Tang, N., Poon, T. (eds) Chemical Diagnostics. Topics in Current Chemistry, vol 336. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_325

Download citation

Publish with us

Policies and ethics

Search

Navigation