1,259
Views
53
CrossRef citations to date
0
Altmetric
Reviews

Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities

, , , &

References

  • Yang Y, Muzny DM, Xia F, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 2014;312(18):1870-9
  • Harding KE, Robertson NP. Applications of next-generation whole exome sequencing. J Neurol 2014;261(6):1244-6
  • Frebourg T. The challenge for the next generation of medical geneticists. Hum Mutat 2014;35(8):909-11
  • Xue Y, Ankala A, Wilcox WR, Hegde MR. Solving the molecular diagnostic testing conundrum for Mendelian disorders in the era of next-generation sequencing: single-gene, gene panel, or exome/genome sequencing. Genet Med 2014. [Epub ahead of print]
  • Williams ES, Hegde M. Implementing genomic medicine in pathology. Adv Anat Pathol 2013;20(4):238-44
  • Pinxten W, Howard HC. Ethical issues raised by whole genome sequencing. Best Pract Res Clin Gastroenterol 2014;28(2):269-79
  • Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 2014;6(265):265ra168
  • Srivastava S, Cohen JS, Vernon H, et al. Clinical whole exome sequencing in child neurology practice. Ann Neurol 2014;76(4):473-83
  • Ng SB, Turner EH, Robertson PD, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009;461(7261):272-6
  • Rosenfeld JA, Mason CE, Smith TM. Limitations of the human reference genome for personalized genomics. PLoS One 2012;7(7):e40294
  • Massingham T, Goldman N. All Your Base: a fast and accurate probabilistic approach to base calling. Genome Biol 2012;13(2):R13
  • Babraham bioinformatics. Available from: www.bioinformatics.babraham.ac.uk/projects/fastqc/
  • Picard. Available from: http://picard.sourceforge.net/command-line-overview.shtml
  • Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res 2008;18(11):1851-8
  • Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 2009;25(14):1754-60
  • Kadalayil L, Rafiq S, Rose-Zerilli MJJ, et al. Exome sequence read depth methods for identifying copy number changes. Brief Bioinformatics 2014. [ Epub ahead of print
  • Li H, Handsaker B, Wysoker A, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009;25(16):2078-9
  • Barnes DM. Legal limbo for ecstasy. Science 1988;239(4842):865
  • McKenna A, Hanna M, Banks E, et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010;20(9):1297-303
  • 1000 Genomes Project Consortium. Abecasis GR, Auton A, et al. An integrated map of genetic variation from 1,092 human genomes. Nature 2012;491(7422):56-65
  • O’Rawe J, Jiang T, Sun G, et al. Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Med 2013;5(3):28
  • Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinformatics 2013;14(2):178-92
  • Fu W, O’Connor TD, Jun G, et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 2013;493(7431):216-20
  • Sherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 2001;29(1):308-11
  • ExAC Browser (Beta). Available from: http://exac.broad.institute.org
  • Margulies EH, Blanchette M; NISC Comparative Sequencing ProgramHaussler D, Green ED. Identification and characterization of multi-species conserved sequences. Genome Res 2003;13(12):2507-18
  • Davydov EV, Goode DL, Sirota M, et al. Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput Biol 2010;6(12):e1001025
  • Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res 2010;20(1):110-21
  • Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 2003;31(13):3812-14
  • Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7(4):248-9
  • Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013; Chapter 7;Unit 7.20
  • Stenson PD, Mort M, Ball EV, et al. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet 2014;133(1):1-9
  • Webb AJ, Thorisson GA, Brookes AJ; GEN2PHEN Consortium. An informatics project and online ‘Knowledge Centre’ supporting modern genotype-to-phenotype research. Hum Mutat 2011;32(5):543-50
  • Landrum MJ, Lee JM, Riley GR, et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 2014;42: Database issue D980-5
  • Amberger JS, Bocchini CA, Schiettecatte F, et al. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res 2015;43: Database issue D789-98
  • Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010;38(16):e164
  • Cingolani P, Platts A, Wang LL, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 2012;6(2):80-92
  • The Bioinformatics Knowledgeblog. Available from: http://bioinformatics.knowledgeblog.org
  • Cancer Genome Atlas Research Network. Weinstein JN, Collisson EA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 2013;45(10):1113-20
  • Alkodsi A, Louhimo R, Hautaniemi S. Comparative analysis of methods for identifying somatic copy number alterations from deep sequencing data. Brief Bioinformatics 2014;16(2):242-54
  • Tan R, Wang Y, Kleinstein SE, et al. An evaluation of copy number variation detection tools from whole-exome sequencing data. Hum Mutat 2014;35(7):899-907
  • Wong K-K, Tsang YTM, Shen J, et al. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA. Nucleic Acids Res 2004;32(9):e69
  • Miyatake S, Koshimizu E, Fujita A, et al. Detecting copy-number variations in whole-exome sequencing data using the eXome Hidden Markov Model: an ‘exome-first’ approach. J Hum Genet 2015; Epub ahead of print
  • Nadaf J, Majewski J, Fahiminiya S. ExomeAI: detection of recurrent allelic imbalance in tumors using whole-exome sequencing data. Bioinformatics 2015;31(3):429-31
  • Redon R, Ishikawa S, Fitch KR, et al. Global variation in copy number in the human genome. Nature 2006;444(7118):444-54
  • Stefansson H, Meyer-Lindenberg A, Steinberg S, et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 2014;505(7483):361-6
  • Church DM, Lappalainen I, Sneddon TP, et al. Public data archives for genomic structural variation. Nat Genet 2010;42(10):813-14
  • Firth HV, Richards SM, Bevan AP, et al. DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. Am J Hum Genet 2009;84(4):524-33
  • De Leeuw N, Dijkhuizen T, Hehir-Kwa JY, et al. Diagnostic interpretation of array data using public databases and internet sources. Hum Mutat 2012;33(6):930-40
  • Ravnan JB, Tepperberg JH, Papenhausen P, et al. Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet 2006;43(6):478-89
  • Ionita-Laza I, Rogers AJ, Lange C, et al. Genetic association analysis of copy-number variation (CNV) in human disease pathogenesis. Genomics 2009;93(1):22-6
  • Zhang X. Exome sequencing greatly expedites the progressive research of Mendelian diseases. Front Med 2014;8(1):42-57
  • Ku C-S, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet 2011;129(4):351-70
  • Boycott KM, Vanstone MR, Bulman DE, MacKenzie AE. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nat Rev Genet 2013;14(10):681-91
  • Choi M, Scholl UI, Ji W, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 2009;106(45):19096-101
  • Worthey EA, Mayer AN, Syverson GD, et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 2011;13(3):255-62
  • Landouré G, Sullivan JM, Johnson JO, et al. Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family. Neurology 2012;79(2):192-4
  • McCormick E, Place E, Falk MJ. Molecular genetic testing for mitochondrial disease: from one generation to the next. Neurotherapeutics 2013;10(2):251-61
  • Dinwiddie DL, Smith LD, Miller NA, et al. Diagnosis of mitochondrial disorders by concomitant next-generation sequencing of the exome and mitochondrial genome. Genomics 2013;102(3):148-56
  • Calabrese C, Simone D, Diroma MA, et al. MToolBox: a highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing. Bioinformatics 2014;30(21):3115-17
  • Wong L-JC. Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion 2013;13(4):379-87
  • Mardis ER, Wilson RK. Cancer genome sequencing: a review. Hum Mol Genet 2009;18(R2):R163-8
  • Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960;25:85-109
  • Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med 2008;359(20):2143-53
  • Wang L, Wheeler DA. Genomic sequencing for cancer diagnosis and therapy. Annu Rev Med 2014;65:33-48
  • Schwartzentruber J, Korshunov A, Liu X-Y, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012;482(7384):226-31
  • Yoshida K, Sanada M, Shiraishi Y, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478(7367):64-9
  • Yan X-J, Xu J, Gu Z-H, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011;43(4):309-15
  • Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet 2014;59(1):5-15
  • Vasen HFA, Tomlinson I, Castells A. Clinical management of hereditary colorectal cancer syndromes. Nat Rev Gastroenterol Hepatol 2015;12:88-97
  • Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 2014;371(26):2477-87
  • Parsons DW, Roy A, Monzon FA, et al. Abstract IA16: Evaluating the implementation and utility of clinical tumor exome sequencing in the pediatric oncology clinic: Early results of the BASIC3 study. Cancer Res 2014;74(20 Suppl):IA16-16
  • Catenacci DVT. Next-generation clinical trials: Novel strategies to address the challenge of tumor molecular heterogeneity. Mol Oncol 2014; Epub ahead of print
  • Jiang T, Tan M-S, Tan L, Yu J-T. Application of next-generation sequencing technologies in Neurology. Ann Transl Med 2014;2(12):125
  • Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature 2009;461(7265):747-53
  • Marian AJ. Challenges in medical applications of whole exome/genome sequencing discoveries. Trends Cardiovasc Med 2012;22(8):219-23
  • Kuechler A, Willemsen MH, Albrecht B, et al. De novo mutations in beta-catenin (CTNNB1) appear to be a frequent cause of intellectual disability: expanding the mutational and clinical spectrum. Hum Genet 2015;134(1):97-109
  • Bonnefond A, Durand E, Sand O, et al. Molecular diagnosis of neonatal diabetes mellitus using next-generation sequencing of the whole exome. PLoS One 2010;5(10):e13630
  • Repas TB, Tanner JR. Preventing early cardiovascular death in patients with familial hypercholesterolemia. J Am Osteopath Assoc 2014;114(2):99-108
  • Van Zelst-Stams WA, Scheffer H, Veltman JA. Clinical exome sequencing in daily practice: 1,000 patients and beyond. Genome Med 2014;6(1):2
  • Atwal PS, Brennan M-L, Cox R, et al. Clinical whole-exome sequencing: are we there yet? Genet Med 2014;16(9):717-19
  • Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med 2014;371(12):1170
  • Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med 2013;369(16):1502-11
  • Levenson D. Whole-exome sequencing emerges as clinical diagnostic tool: testing method proves useful for diagnosing wide range of genetic disorders. Am J Med Genet A 2014;164A(1):ix-x
  • Retterer K, Scuffins J, Schmidt D, et al. Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort. Genet Med 2014;16:11
  • De Ligt J, Boone PM, Pfundt R, et al. Detection of clinically relevant copy number variants with whole-exome sequencing. Hum Mutat 2013;34(10):1439-48
  • Poultney CS, Goldberg AP, Drapeau E, et al. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am J Hum Genet 2013;93(4):607-19
  • Gilissen C, Hehir-Kwa JY, Thung DT, et al. Genome sequencing identifies major causes of severe intellectual disability. Nature 2014;511(7509):344-7
  • Strom SP, Lee H, Das K, et al. Assessing the necessity of confirmatory testing for exome-sequencing results in a clinical molecular diagnostic laboratory. Genet Med 2014;16(7):510-15
  • Van El CG, Cornel MC, Borry P, et al. Whole-genome sequencing in health care: recommendations of the European Society of Human Genetics. Eur J Hum Genet 2013;21(6):580-4
  • Drmanac R, Sparks AB, Callow MJ, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 2010;327(5961):78-81
  • Ku CS, Polychronakos C, Tan EK, et al. A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease. Mol Psychiatry 2013;18(2):141-53

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.