Defining the Clinical Value of a Genomic Diagnosis in the Era of Next-Generation Sequencing

Literature Cited

1. 1. ACMG Board Dir 2015. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet. Med. 17:505–7 [Google Scholar]
2. Adams MC, Berg JS, Pearlman MD, Vora NL. 2.  2015. Look before you leap: genomic screening in obstetrics and gynecology. Obstet. Gynecol. 125:1299–305 [Google Scholar]
3. 3. Am. Soc. Hum. Genet. Board Dir., Am. Coll. Med. Genet. Board Dir 1995. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am. J. Hum. Genet. 57:1233–41 [Google Scholar]
4. Amendola LM, Horike-Pyne M, Trinidad SB, Fullerton SM, Evans BJ. 4.  et al. 2015. Patients’ choices for return of exome sequencing results to relatives in the event of their death. J. Law Med. Ethics 43:476–85 [Google Scholar]
5. Arora S, Haverfield E, Richard G, Haga SB, Mills R. 5.  2016. Clinical and counseling experiences of early adopters of whole exome sequencing. J. Genet. Couns. 25:337–43 [Google Scholar]
6. Ashley EA. 6.  2015. The Precision Medicine Initiative: a new national effort. JAMA 313:2119–20 [Google Scholar]
7. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ. 7.  et al. 2011. Exome sequencing as a tool for Mendelian disease gene discovery. Nat. Rev. Genet. 12:745–55 [Google Scholar]
8. Bao R, Huang L, Andrade J, Tan W, Kibbe WA. 8.  et al. 2014. Review of current methods, applications, and data management for the bioinformatics analysis of whole exome sequencing. Cancer Inform. 13:67–82 [Google Scholar]
9. Beale S, Sanderson D, Sanniti A, Dundar Y, Boland A. 9.  2015. A scoping study to explore the cost-effectiveness of next-generation sequencing compared with traditional genetic testing for the diagnosis of learning disabilities in children. Health Technol. Assess. 19:1–90 [Google Scholar]
10. Beaulieu CL, Majewski J, Schwartzentruber J, Samuels ME, Fernandez BA. 10.  et al. 2014. FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project. Am. J. Hum. Genet. 94:809–17 [Google Scholar]
11. Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB. 11.  et al. 2015. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. PNAS 112:5473–78 [Google Scholar]
12. Bennette CS, Gallego CJ, Burke W, Jarvik GP, Veenstra DL. 12.  2015. The cost-effectiveness of returning incidental findings from next-generation genomic sequencing. Genet. Med. 17:587–95 [Google Scholar]
13. Berg JS. 13.  2014. Genome-scale sequencing in clinical care: establishing molecular diagnoses and measuring value. JAMA 312:1865–67 [Google Scholar]
14. Berg JS, Adams M, Nassar N, Bizon C, Lee K. 14.  et al. 2013. An informatics approach to analyzing the incidentalome. Genet. Med. 15:36–44 [Google Scholar]
15. Berg JS, Amendola LM, Eng C, Van Allen E, Gray SW. 15.  et al. 2013. Processes and preliminary outputs for identification of actionable genes as incidental findings in genomic sequence data in the Clinical Sequencing Exploratory Research Consortium. Genet. Med. 15:860–67 [Google Scholar]
16. Berg JS, Foreman AKM, O'Daniel JM, Booker JK, Boshe L. 16.  et al. 2016. A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing. Genet. Med. 18:467–75 [Google Scholar]
17. Berg JS, Khoury MJ, Evans JP. 17.  2011. Deploying whole genome sequencing in clinical practice and public health: meeting the challenge one bin at a time. Genet. Med. 13:499–504 [Google Scholar]
18. Beryozkin A, Shevah E, Kimchi A, Mizrahi-Meissonnier L, Khateb S. 18.  et al. 2015. Whole exome sequencing reveals mutations in known retinal disease genes in 33 out of 68 Israeli families with inherited retinopathies. Sci. Rep. 5:13187 [Google Scholar]
19. Biesecker LG, Green RC. 19.  2014. Diagnostic clinical genome and exome sequencing. N. Engl. J. Med. 370:2418–25 [Google Scholar]
20. Bird TD. 20.  2015. Charcot-Marie-Tooth hereditary neuropathy overview. GeneReviews RA Pagon, MP Adam, HH Ardinger, SE Wallace, A Amemiya et al. Seattle, WA: Univ. Wash. Press http://www.ncbi.nlm.nih.gov/books/NBK1358 [Google Scholar]
21. Blackburn HL, Schroeder B, Turner C, Shriver CD, Ellsworth DL, Ellsworth RE. 21.  2015. Management of incidental findings in the era of next-generation sequencing. Curr. Genom. 16:159–74 [Google Scholar]
22. Bloss CS, Zeeland AA, Topol SE, Darst BF, Boeldt DL. 22.  et al. 2015. A genome sequencing program for novel undiagnosed diseases. Genet. Med. 17:995–1001 [Google Scholar]
23. Bosmans JM, Schrans D, Avonts D, De Maeseneer JM. 23.  2014. Communication between general practitioners and radiologists: opinions, experience, promises, pitfalls. JBR-BTR 97:325–30 [Google Scholar]
24. Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y. 24.  et al. 2015. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am. J. Hum. Genet. 97:6–21 [Google Scholar]
25. Bredenoord AL, de Vries MC, van Delden JJM. 25.  2013. Next-generation sequencing: Does the next generation still have a right to an open future?. Nat. Rev. Genet. 14:306 [Google Scholar]
26. Breitkopf CR, Petersen GM, Wolf SM, Chaffee KG, Robinson ME. 26.  et al. 2015. Preferences regarding return of genomic results to relatives of research participants, including after participant death: empirical results from a cancer biobank. J. Law Med. Ethics 43:464–75 [Google Scholar]
27. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR. 27.  et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. PNAS 106:19096–101 [Google Scholar]
28. Chong JX, Buckingham KJ, Jhangiani SN, Boehm C, Sobreira N. 28.  et al. 2015. The genetic basis of Mendelian phenotypes: discoveries, challenges, and opportunities. Am. J. Hum. Genet. 97:199–215 [Google Scholar]
29. 29. Comm. Bioeth., Comm. Genet., Am. Coll. Med. Genet. Genom. Soc. Ethical Leg. Issues Comm 2013. Ethical and policy issues in genetic testing and screening of children. Pediatrics 131:620–22 [Google Scholar]
30. Conley ME, Casanova JL. 30.  2014. Discovery of single-gene inborn errors of immunity by next generation sequencing. Curr. Opin. Immunol. 30:17–23 [Google Scholar]
31. Conti R, Veenstra DL, Armstrong K, Lesko LJ, Grosse SD. 31.  2010. Personalized medicine and genomics: challenges and opportunities in assessing effectiveness, cost-effectiveness, and future research priorities. Med. Decis. Mak. 30:328–40 [Google Scholar]
32. Cooper DN, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H. 32.  2013. Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum. Genet. 132:1077–130 [Google Scholar]
33. Davis DS. 33.  1997. Genetic dilemmas and the child's right to an open future. Hastings Cent. Rep. 27:7–15 [Google Scholar]
34. de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG. 34.  et al. 2012. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367:1921–29 [Google Scholar]
35. Dickenson DL. 35.  1999. Can children and young people consent to be tested for adult onset genetic disorders?. BMJ 318:1063–65 [Google Scholar]
36. Dimassi S, Labalme A, Ville D, Calender A, Mignot C. 36.  et al. 2016. Whole-exome sequencing improves the diagnosis yield in sporadic infantile spasm syndrome. Clin. Genet. 89:198–204 [Google Scholar]
37. Esplin ED, Oei L, Snyder MP. 37.  2014. Personalized sequencing and the future of medicine: discovery, diagnosis and defeat of disease. Pharmacogenomics 15:1771–90 [Google Scholar]
38. Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM. 38.  et al. 2010. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ. Cardiovasc. Genet. 3:574–80 [Google Scholar]
39. Farwell KD, Shahmirzadi L, El-Khechen D, Powis Z, Chao EC. 39.  et al. 2015. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet. Med. 17:578–86 [Google Scholar]
40. Foley SB, Rios JJ, Mgbemena VE, Robinson LS, Hampel HL. 40.  et al. 2015. Use of whole genome sequencing for diagnosis and discovery in the cancer genetics clinic. EBioMedicine 2:74–81 [Google Scholar]
41. Gahl WA, Markello TC, Toro C, Fajardo KF, Sincan M. 41.  et al. 2012. The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases. Genet. Med. 14:51–59 [Google Scholar]
42. Gargis AS, Kalman L, Bick DP, da Silva C, Dimmock DP. 42.  et al. 2015. Good laboratory practice for clinical next-generation sequencing informatics pipelines. Nat. Biotechnol. 33:689–93 [Google Scholar]
43. Gilissen C, Hehir-Kwa JY, Thung DT, van de Vorst M, van Bon BW. 43.  et al. 2014. Genome sequencing identifies major causes of severe intellectual disability. Nature 511:344–47 [Google Scholar]
44. Gilissen C, Hoischen A, Brunner HG, Veltman JA. 44.  2011. Unlocking Mendelian disease using exome sequencing. Genome Biol. 12:228 [Google Scholar]
45. Gilissen C, Hoischen A, Brunner HG, Veltman JA. 45.  2012. Disease gene identification strategies for exome sequencing. Eur. J. Hum. Genet. 20:490–97 [Google Scholar]
46. Goddard KA, Whitlock EP, Berg JS, Williams MS, Webber EM. 46.  et al. 2013. Description and pilot results from a novel method for evaluating return of incidental findings from next-generation sequencing technologies. Genet. Med. 15:721–28 [Google Scholar]
47. Goecks J, Nekrutenko A, Taylor J, Galaxy T. 47.  2010. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol. 11:R86 [Google Scholar]
48. Gold WA, Christodoulou J. 48.  2015. The utility of next-generation sequencing in gene discovery for mutation-negative patients with Rett syndrome. Front. Cell Neurosci. 9:266 [Google Scholar]
49. González-del Pozo M, Méndez-Vidal C, Bravo-Gil N, Vela-Boza A, Dopazo J. 49.  et al. 2014. Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies. PLOS ONE 9:e116176 [Google Scholar]
50. Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock DP. 50.  et al. 2012. Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet. Med. 14:405–10 [Google Scholar]
51. Green RC, Berg JS, Grody WW, Kalia SS, Korf BR. 51.  et al. 2013. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15:565–74 [Google Scholar]
52. Grosse SD, Khoury MJ. 52.  2006. What is the clinical utility of genetic testing?. Genet. Med. 8:448–50 [Google Scholar]
53. Halbritter F, Vaidya HJ, Tomlinson SR. 53.  2012. GeneProf: analysis of high-throughput sequencing experiments. Nat. Methods 9:7–8 [Google Scholar]
54. Higashi MK, Veenstra DL. 54.  2003. Managed care in the genomics era: assessing the cost effectiveness of genetic tests. Am. J. Manag. Care 9:493–500 [Google Scholar]
55. Holtzman NA, Watson MS. 55.  1999. Promoting safe and effective genetic testing in the United States. Final report of the Task Force on Genetic Testing. J. Child Fam. Nurs. 2:388–90 [Google Scholar]
56. Hoyle JC, Isfort MC, Roggenbuck J, Arnold WD. 56.  2015. The genetics of Charcot-Marie-Tooth disease: current trends and future implications for diagnosis and management. Appl. Clin. Genet. 8:235–43 [Google Scholar]
57. Iglesias A, Anyane-Yeboa K, Wynn J, Wilson A, Cho MT. 57.  et al. 2014. The usefulness of whole-exome sequencing in routine clinical practice. Genet. Med. 16:922–31 [Google Scholar]
58. Janssens AC, van Duijn CM. 58.  2008. Genome-based prediction of common diseases: advances and prospects. Hum. Mol. Genet. 17:R166–73 [Google Scholar]
59. Kassahn KS, Scott HS, Caramins MC. 59.  2014. Integrating massively parallel sequencing into diagnostic workflows and managing the annotation and clinical interpretation challenge. Hum. Mutat. 35:413–23 [Google Scholar]
60. Katsanis SH, Katsanis N. 60.  2013. Molecular genetic testing and the future of clinical genomics. Nat. Rev. Genet. 14:415–26 [Google Scholar]
61. Klee EW, Hoppman-Chaney NL, Ferber MJ. 61.  2011. Expanding DNA diagnostic panel testing: Is more better?. Expert Rev. Mol. Diagn. 11:703–9 [Google Scholar]
62. Klitzman R, Appelbaum PS, Fyer A, Martinez J, Buquez B. 62.  et al. 2013. Researchers’ views on return of incidental genomic research results: qualitative and quantitative findings. Genet. Med. 15:888–95 [Google Scholar]
63. Kohler S, Doelken SC, Mungall CJ, Bauer S, Firth HV. 63.  et al. 2014. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res. 42:D966–74 [Google Scholar]
64. Korf BR, Rehm HL. 64.  2013. New approaches to molecular diagnosis. JAMA 309:1511–21 [Google Scholar]
65. Kotliarov Y, Bozdag S, Cheng H, Wuchty S, Zenklusen JC, Fine HA. 65.  2010. CNAReporter: a GenePattern pipeline for the generation of clinical reports of genomic alterations. BMC Med. Genom. 3:11 [Google Scholar]
66. Ku CS, Cooper DN, Polychronakos C, Naidoo N, Wu M, Soong R. 66.  2012. Exome sequencing: dual role as a discovery and diagnostic tool. Ann. Neurol. 71:5–14 [Google Scholar]
67. Landrum MJ, Lee JM, Benson M, Brown G, Chao C. 67.  et al. 2016. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44:D862–68 [Google Scholar]
68. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S. 68.  et al. 2014. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312:1880–87 [Google Scholar]
69. Lee K, Berg JS, Milko L, Crooks K, Lu M. 69.  et al. 2015. High diagnostic yield of whole exome sequencing in participants with retinal dystrophies in a clinical ophthalmology setting. Am. J. Ophthalmol. 160:354–63e9 [Google Scholar]
70. Lohmann K, Klein C. 70.  2014. Next generation sequencing and the future of genetic diagnosis. Neurotherapeutics 11:699–707 [Google Scholar]
71. Lushbough CM, Brendel VP. 71.  2010. An overview of the BioExtract Server: a distributed, Web-based system for genomic analysis. Adv. Exp. Med. Biol. 680:361–69 [Google Scholar]
72. Mardis ER. 72.  2011. A decade's perspective on DNA sequencing technology. Nature 470:198–203 [Google Scholar]
73. Matthijs G, Souche E, Alders M, Corveleyn A, Eck S. 73.  et al. 2015. Guidelines for diagnostic next-generation sequencing. Eur. J. Hum. Genet. 24:2–5 [Google Scholar]
74. McLaughlin HM, Ceyhan-Birsoy O, Christensen KD, Kohane IS, Krier J. 74.  et al. 2014. A systematic approach to the reporting of medically relevant findings from whole genome sequencing. BMC Med. Genet. 15:134 [Google Scholar]
75. McPherson E. 75.  2006. Genetic diagnosis and testing in clinical practice. Clin. Med. Res. 4:123–29 [Google Scholar]
76. Middha S, Lindor NM, McDonnell SK, Olson JE, Johnson KJ. 76.  et al. 2015. How well do whole exome sequencing results correlate with medical findings? A study of 89 Mayo Clinic Biobank samples. Front. Genet. 6:244 [Google Scholar]
77. Middleton A, Morley KI, Bragin E, Firth HV, Hurles ME. 77.  et al. 2015. Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research. Eur. J. Hum. Genet. 24:21–29 [Google Scholar]
78. Miles JH. 78.  2011. Autism spectrum disorders—a genetics review. Genet. Med. 13:278–94 [Google Scholar]
79. Millum J. 79.  2014. The foundation of the child's right to an open future. J. Soc. Philos. 45:522–38 [Google Scholar]
80. Morey M, Fernández-Marmiesse A, Castiñeiras D, Fraga JM, Couce ML, Cocho JA. 80.  2013. A glimpse into past, present, and future DNA sequencing. Mol. Genet. Metab. 110:3–24 [Google Scholar]
81. Narula N, Tester DJ, Paulmichl A, Maleszewski JJ, Ackerman MJ. 81.  2015. Post-mortem whole exome sequencing with gene-specific analysis for autopsy-negative sudden unexplained death in the young: a case series. Pediatr. Cardiol. 36:768–78 [Google Scholar]
82. Need AC, Shashi V, Hitomi Y, Schoch K, Shianna KV. 82.  et al. 2012. Clinical application of exome sequencing in undiagnosed genetic conditions. J. Med. Genet. 49:353–61 [Google Scholar]
83. Nekrutenko A, Taylor J. 83.  2012. Next-generation sequencing data interpretation: enhancing reproducibility and accessibility. Nat. Rev. Genet. 13:667–72 [Google Scholar]
84. Neron B, Menager H, Maufrais C, Joly N, Maupetit J. 84.  et al. 2009. Mobyle: a new full web bioinformatics framework. Bioinformatics 25:3005–11 [Google Scholar]
85. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW. 85.  et al. 2009. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461:272–76 [Google Scholar]
86. Norwitz ER, Levy B. 86.  2013. Noninvasive prenatal testing: the future is now. Rev. Obstet. Gynecol. 6:48–62 [Google Scholar]
87. Nunn LM, Lopes LR, Syrris P, Murphy C, Plagnol V. 87.  et al. 2016. Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing. Europace 18888–96
88. O'Rawe J, Jiang T, Sun G, Wu Y, Wang W. 88.  et al. 2013. Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Med. 5:28 [Google Scholar]
89. Pabinger S, Dander A, Fischer M, Snajder R, Sperk M. 89.  et al. 2014. A survey of tools for variant analysis of next-generation genome sequencing data. Brief. Bioinform. 15:256–78 [Google Scholar]
90. Pepin MG, Murray ML, Bailey S, Leistritz-Kessler D, Schwarze U, Byers PH. 90.  2016. The challenge of comprehensive and consistent sequence variant interpretation between clinical laboratories. Genet. Med. 18:20–24 [Google Scholar]
91. Posey JE, Rosenfeld JA, James RA, Bainbridge M, Niu Z. 91.  et al. 2016. Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet. Med. 18678–85
92. Powsner SM, Costa J, Homer RJ. 92.  2000. Clinicians are from Mars and pathologists are from Venus. Arch. Pathol. Lab. Med. 124:1040–46 [Google Scholar]
93. Quail MA, Smith M, Coupland P, Otto TD, Harris SR. 93.  et al. 2012. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genom. 13:341 [Google Scholar]
94. Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I. 94.  2012. Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. J. Hum. Genet. 57:621–32 [Google Scholar]
95. Rehm HL. 95.  2013. Disease-targeted sequencing: a cornerstone in the clinic. Nat. Rev. Genet. 14:295–300 [Google Scholar]
96. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK. 96.  et al. 2013. ACMG clinical laboratory standards for next-generation sequencing. Genet. Med. 15:733–47 [Google Scholar]
97. Rehm HL, Berg JS, Brooks LD, Bustamante CD, Evans JP. 97.  et al. 2015. ClinGen—the Clinical Genome Resource. N. Engl. J. Med. 372:2235–42 [Google Scholar]
98. Reich M, Liefeld T, Gould J, Lerner J, Tamayo P, Mesirov JP. 98.  2006. GenePattern 2.0. Nat. Genet. 38:500–1 [Google Scholar]
99. Retterer K, Juusola J, Cho MT, Vitazka P, Millan F. 99.  et al. 2016. Clinical application of whole-exome sequencing across clinical indications. Genet. Med. 18696–704
100. Reuter JA, Spacek DV, Snyder MP. 100.  2015. High-throughput sequencing technologies. Mol. Cell 58:586–97 [Google Scholar]
101. Richards S, Aziz N, Bale S, Bick D, Das S. 101.  et al. 2015. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17:405–24 [Google Scholar]
102. Rosenstein BJ, Cutting GR. 102.  1998. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J. Pediatr. 132:589–95 [Google Scholar]
103. Ross LF, Saal HM, David KL, Anderson RR. 103.  Am. Acad. Pediatr., Am. Coll. Med. Genet. Genom 2013. Technical report: ethical and policy issues in genetic testing and screening of children. Genet. Med. 15:234–45 [Google Scholar]
104. Rossor AM, Polke JM, Houlden H, Reilly MM. 104.  2013. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat. Rev. Neurol. 9:562–71 [Google Scholar]
105. Ruby SG. 105.  2000. Clinician interpretation of pathology reports: confusion or comprehension?. Arch. Pathol. Lab. Med. 124:943–44 [Google Scholar]
106. Sajantila A, Budowle B. 106.  2016. Postmortem medicolegal genetic diagnostics also require reporting guidance. Eur. J. Hum. Genet. 24:329–30 [Google Scholar]
107. Salto-Tellez M, Gonzalez de Castro D. 107.  2014. Next-generation sequencing: a change of paradigm in molecular diagnostic validation. J. Pathol. 234:5–10 [Google Scholar]
108. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ. 108.  et al. 2012. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485:237–41 [Google Scholar]
109. 109. Saudi Mendeliome Group 2015. Comprehensive gene panels provide advantages over clinical exome sequencing for Mendelian diseases. Genome Biol. 16:134 [Google Scholar]
110. Sawyer SL, Hartley T, Dyment DA, Beaulieu CL, Schwartzentruber J. 110.  et al. 2016. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin. Genet. 89:275–84 [Google Scholar]
111. Schrijver I, Farkas DH, Gibson JS, Lyon E. 111.  (AMP Exec. Comm.) 2015. The evolving role of the laboratory professional in the age of genome sequencing: a vision of the association for molecular pathology. J. Mol. Diagn. 17:335–38 [Google Scholar]
112. Shalowitz DI, Miller FG. 112.  2005. Disclosing individual results of clinical research: implications of respect for participants. JAMA 294:737–40 [Google Scholar]
113. Shashi V, McConkie-Rosell A, Schoch K, Kasturi V, Rehder C. 113.  et al. 2016. Practical considerations in the clinical application of whole-exome sequencing. Clin. Genet. 89:173–81 [Google Scholar]
114. Shen T, Pajaro-Van de Stadt SH, Yeat NC, Lin JC. 114.  2015. Clinical applications of next generation sequencing in cancer: from panels, to exomes, to genomes. Front. Genet. 6:215 [Google Scholar]
115. Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW. 115.  2013. Pleiotropy in complex traits: challenges and strategies. Nat. Rev. Genet. 14:483–95 [Google Scholar]
116. Stranneheim H, Wedell A. 116.  2015. Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders. J. Intern. Med. 279:3–15 [Google Scholar]
117. Sun Y, Ruivenkamp CA, Hoffer MJ, Vrijenhoek T, Kriek M. 117.  et al. 2015. Next-generation diagnostics: gene panel, exome, or whole genome?. Hum. Mutat. 36:648–55 [Google Scholar]
118. Tacik P, Guthrie KJ, Strongosky AJ, Broderick DF, Riegert-Johnson DL. 118.  et al. 2015. Whole-exome sequencing as a diagnostic tool in a family with episodic ataxia type 1. Mayo Clin. Proc. 90:366–71 [Google Scholar]
119. Tammimies K, Marshall CR, Walker S, Kaur G, Thiruvahindrapuram B. 119.  et al. 2015. Molecular diagnostic yield of chromosomal microarray analysis and whole-exome sequencing in children with autism spectrum disorder. JAMA 314:895–903 [Google Scholar]
120. Taylor JC, Martin HC, Lise S, Broxholme J, Cazier JB. 120.  et al. 2015. Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat. Genet. 47:717–26 [Google Scholar]
121. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J. 121.  et al. 2014. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA 312:68–77 [Google Scholar]
122. Tetreault M, Bareke E, Nadaf J, Alirezaie N, Majewski J. 122.  2015. Whole-exome sequencing as a diagnostic tool: current challenges and future opportunities. Expert Rev. Mol. Diagn. 15:749–60 [Google Scholar]
123. Tsai AC, Liu X. 123.  2014. Toward best practice in using molecular diagnosis to guide medical management, are we there yet?. N. Am. J. Med. Sci. 7:199–200 [Google Scholar]
124. Tsurusaki Y, Kobayashi Y, Hisano M, Ito S, Doi H. 124.  et al. 2013. The diagnostic utility of exome sequencing in Joubert syndrome and related disorders. J. Hum. Genet. 58:113–15 [Google Scholar]
125. Valencia CA, Husami A, Holle J, Johnson JA, Qian Y. 125.  et al. 2015. Clinical impact and cost-effectiveness of whole exome sequencing as a diagnostic tool: a pediatric center's experience. Front. Pediatr. 3:67 [Google Scholar]
126. van El CG, Cornel MC, Borry P, Hastings RJ, Fellmann F. 126.  et al. 2013. Whole-genome sequencing in health care: recommendations of the European Society of Human Genetics. Eur. J. Hum. Genet. 21:580–84 [Google Scholar]
127. Weiner C. 127.  2014. Anticipate and communicate: ethical management of incidental and secondary findings in the clinical, research, and direct-to-consumer contexts (December 2013 report of the Presidential Commission for the Study of Bioethical Issues). Am. J. Epidemiol. 180:562–64 [Google Scholar]
128. Weiss MM, Van der Zwaag B, Jongbloed JDH, Vogel MJ, Brüggenwirth HT. 128.  et al. 2013. Best practice guidelines for the use of next-generation sequencing applications in genome diagnostics: a national collaborative study of Dutch genome diagnostic laboratories. Hum. Mutat. 34:1313–21 [Google Scholar]
129. Wolf SM, Branum R, Koenig BA, Petersen GM, Berry SA. 129.  et al. 2015. Returning a research participant's genomic results to relatives: analysis and recommendations. J. Law Med. Ethics 43:440–63 [Google Scholar]
130. Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP. 130.  et al. 2012. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet. Med. 14:361–84 [Google Scholar]
131. Wright CF, Fitzgerald TW, Jones WD, Clayton S, McRae JF. 131.  et al. 2015. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet 385:1305–14 [Google Scholar]
132. Xue Y, Ankala A, Wilcox WR, Hegde MR. 132.  2015. 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. 17:444–51 [Google Scholar]
133. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A. 133.  et al. 2013. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N. Engl. J. Med. 369:1502–11 [Google Scholar]
134. Yang Y, Muzny DM, Xia F, Niu Z, Person R. 134.  et al. 2014. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312:1870–79 [Google Scholar]
135. Yu TW, Chahrour MH, Coulter ME, Jiralerspong S, Okamura-Ikeda K. 135.  et al. 2013. Using whole-exome sequencing to identify inherited causes of autism. Neuron 77:259–73 [Google Scholar]
136. Zhu X, Petrovski S, Xie P, Ruzzo EK, Lu YF. 136.  et al. 2015. Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. Genet. Med. 17:774–81 [Google Scholar]