Genomic Medicine–Progress, Pitfalls, and Promise

Cell

Volumn 177, Issue 1, 2019, Pages 45-57

  Shendure, Jay ^a,b,c   Findlay, Gregory M ^a   Snyder, Matthew W ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c BROTMAN BATY INSTITUTE FOR PRECISION MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENO ASSOCIATED VIRUS VECTOR; BLOOD CLOTTING FACTOR 8; DYSTROPHIN; GEFITINIB; HEMOGLOBIN BETA CHAIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IVACAFTOR; LENTIVIRUS VECTOR; LUMACAFTOR;

AUTISM; CORONARY ARTERY DISEASE; CYSTIC FIBROSIS; DRUG EFFECT; DRUG EFFICACY; DUCHENNE MUSCULAR DYSTROPHY; FAMILIAL HYPERCHOLESTEROLEMIA; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENETIC SUSCEPTIBILITY; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; GENOTYPE; HEMOPHILIA A; HERITABILITY; HUMAN; HUMAN GENOME PROJECT; INTELLECTUAL IMPAIRMENT; NEXT GENERATION SEQUENCING; NON SMALL CELL LUNG CANCER; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SANGER SEQUENCING; SICKLE CELL ANEMIA; SINGLE DRUG DOSE; VIRAL GENE THERAPY; GENETIC SCREENING; GENETICS; HUMAN GENOME; PERSONALIZED MEDICINE; PROCEDURES;

GENETIC TESTING; GENOME, HUMAN; GENOMICS; HUMAN GENOME PROJECT; HUMANS; PRECISION MEDICINE;

EID: 85062727854     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2019.02.003     Document Type: Review

References (107)

1. Bailey, M.H., Tokheim, C., Porta-Pardo, E., Sengupta, S., Bertrand, D., Weerasinghe, A., Colaprico, A., Wendl, M.C., Kim, J., Reardon, B., et al. MC3 Working Group, Cancer Genome Atlas Research Network. Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell 173 (2018), 371–385.e18.
2. Baird, P.A., Anderson, T.W., Newcombe, H.B., Lowry, R.B., Genetic disorders in children and young adults: a population study. Am. J. Hum. Genet. 42 (1988), 677–693.
3. Bernier, R., Golzio, C., Xiong, B., Stessman, H.A., Coe, B.P., Penn, O., Witherspoon, K., Gerdts, J., Baker, C., Vulto-van Silfhout, A.T., et al. Disruptive CHD8 mutations define a subtype of autism early in development. Cell 158 (2014), 263–276.
4. Bettegowda, C., Sausen, M., Leary, R.J., Kinde, I., Wang, Y., Agrawal, N., Bartlett, B.R., Wang, H., Luber, B., Alani, R.M., et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med., 6, 2014, 224ra24.
5. Bianchi, D.W., Parker, R.L., Wentworth, J., Madankumar, R., Saffer, C., Das, A.F., Craig, J.A., Chudova, D.I., Devers, P.L., Jones, K.W., et al., CARE Study Group. DNA sequencing versus standard prenatal aneuploidy screening. N. Engl. J. Med. 370 (2014), 799–808.
6. Boyle, E.A., Li, Y.I., Pritchard, J.K., An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell 169 (2017), 1177–1186.
7. Burdett, T., Hastings, E., Welter, D., SPOT, EMBL-EBI, and NHGRI. 2018, GWAS Catalog.
8. Bycroft, C., Freeman, C., Petkova, D., Band, G., Elliott, L.T., Sharp, K., Motyer, A., Vukcevic, D., Delaneau, O., O'Connell, J., et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562 (2018), 203–209.
9. Camunas-Soler, J., Lee, H., Hudgins, L., Hintz, S.R., Blumenfeld, Y.J., El-Sayed, Y.Y., Quake, S.R., Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR. Clin. Chem. 64 (2018), 336–345.
10. Chan, K.C.A., Jiang, P., Sun, K., Cheng, Y.K.Y., Tong, Y.K., Cheng, S.H., Wong, A.I.C., Hudecova, I., Leung, T.Y., Chiu, R.W.K., Lo, Y.M., Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends. Proc. Natl. Acad. Sci. USA 113 (2016), E8159–E8168.
11. Chan, K.C.A., Woo, J.K.S., King, A., Zee, B.C.Y., Lam, W.K.J., Chan, S.L., Chu, S.W.I., Mak, C., Tse, I.O.L., Leung, S.Y.M., et al. Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N. Engl. J. Med. 377 (2017), 513–522.
12. Chaudhary, R., Garg, J., Shah, N., Sumner, A., PCSK9 inhibitors: A new era of lipid lowering therapy. World J. Cardiol. 9 (2017), 76–91.
13. Chiu, R.W.K., Chan, K.C.A., Gao, Y., Lau, V.Y.M., Zheng, W., Leung, T.Y., Foo, C.H.F., Xie, B., Tsui, N.B.Y., Lun, F.M.F., et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc. Natl. Acad. Sci. USA 105 (2008), 20458–20463.
14. Choi, M., Scholl, U.I., Ji, W., Liu, T., Tikhonova, I.R., Zumbo, P., Nayir, A., Bakkaloğlu, A., Ozen, S., Sanjad, S., et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl. Acad. Sci. USA 106 (2009), 19096–19101.
15. Chong, J.X., Buckingham, K.J., Jhangiani, S.N., Boehm, C., Sobreira, N., Smith, J.D., Harrell, T.M., McMillin, M.J., Wiszniewski, W., Gambin, T., et al., Centers for Mendelian Genomics. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities. Am. J. Hum. Genet. 97 (2015), 199–215.
16. Cohen, J.D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A.A., Wong, F., Mattox, A., et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359 (2018), 926–930.
17. Collins, F.S., Guyer, M.S., Charkravarti, A., Variations on a theme: cataloging human DNA sequence variation. Science 278 (1997), 1580–1581.
18. Couch, F.J., Wang, X., McGuffog, L., Lee, A., Olswold, C., Kuchenbaecker, K.B., Soucy, P., Fredericksen, Z., Barrowdale, D., Dennis, J., et al. kConFab Investigators SWE-BRCA Ontario Cancer Genetics Network HEBON EMBRACE GEMO Study Collaborators BCFR, CIMBA. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet., 9, 2013, e1003212.
19. Dar, P., Shani, H., Evans, M.I., Cell-free DNA: Comparison of Technologies. Clin. Lab. Med. 36 (2016), 199–211.
20. deVos, T., Tetzner, R., Model, F., Weiss, G., Schuster, M., Distler, J., Steiger, K.V., Grützmann, R., Pilarsky, C., Habermann, J.K., et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin. Chem. 55 (2009), 1337–1346.
21. Dewey, F.E., Gusarova, V., Dunbar, R.L., O'Dushlaine, C., Schurmann, C., Gottesman, O., McCarthy, S., Van Hout, C.V., Bruse, S., Dansky, H.M., et al. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. N. Engl. J. Med. 377 (2017), 211–221.
22. Do, R., Willer, C.J., Schmidt, E.M., Sengupta, S., Gao, C., Peloso, G.M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat. Genet. 45 (2013), 1345–1352.
23. Dunbar, C.E., High, K.A., Joung, J.K., Kohn, D.B., Ozawa, K., Sadelain, M., Gene therapy comes of age. Science, 359, 2018, eaan4672.
24. Eldomery, M.K., Coban-Akdemir, Z., Harel, T., Rosenfeld, J.A., Gambin, T., Stray-Pedersen, A., Küry, S., Mercier, S., Lessel, D., Denecke, J., et al. Lessons learned from additional research analyses of unsolved clinical exome cases. Genome Med., 9, 2017, 26.
25. Erlich, Y., Shor, T., Pe'er, I., Carmi, S., Identity inference of genomic data using long-range familial searches. Science 362 (2018), 690–694.
26. Fan, H.C., Blumenfeld, Y.J., Chitkara, U., Hudgins, L., Quake, S.R., Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc. Natl. Acad. Sci. USA 105 (2008), 16266–16271.
27. Fan, H.C., Gu, W., Wang, J., Blumenfeld, Y.J., El-Sayed, Y.Y., Quake, S.R., Non-invasive prenatal measurement of the fetal genome. Nature 487 (2012), 320–324.
28. Farnaes, L., Hildreth, A., Sweeney, N.M., Clark, M.M., Chowdhury, S., Nahas, S., Cakici, J.A., Benson, W., Kaplan, R.H., Kronick, R., et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. NPJ Genom Med, 3, 2018, 10.
29. Findlay, G.M., Daza, R.M., Martin, B., Zhang, M.D., Leith, A.P., Gasperini, M., Janizek, J.D., Huang, X., Starita, L.M., Shendure, J., Accurate functional classification of thousands of BRCA1 variants with saturation genome editing. Nature 562 (2018), 217–222.
30. Finucane, H.K., Bulik-Sullivan, B., Gusev, A., Trynka, G., Reshef, Y., Loh, P.-R., Anttila, V., Xu, H., Zang, C., Farh, K., et al. ReproGen Consortium Schizophrenia Working Group of the Psychiatric Genomics Consortium, RACI Consortium. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47 (2015), 1228–1235.
31. Fuchsberger, C., Flannick, J., Teslovich, T.M., Mahajan, A., Agarwala, V., Gaulton, K.J., Ma, C., Fontanillas, P., Moutsianas, L., McCarthy, D.J., et al. The genetic architecture of type 2 diabetes. Nature 536 (2016), 41–47.
32. Gaj, T., Gersbach, C.A., Barbas, C.F. 3rd, ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 31 (2013), 397–405.
33. Gasperini, M., Hill, A.J., McFaline-Figueroa, J.L., Martin, B., Kim, S., Zhang, M.D., Jackson, D., Leith, A., Schreiber, J., Noble, W.S., et al. A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens. Cell 176 (2019), 377–390.e19.
34. Gitlin, J.M. (2013). Calculating the economic impact of the Human Genome Project. National Human Genome Research Institute (NHGRI), last updated June 12, 2013. https://www.genome.gov/27544383/calculating-the-economic-impact-of-the-human-genome-project/.
35. Global Genomic Medicine Collaborative (2018). Improving the implementation of: Global Genomic Medicine. https://g2mc.org/.
36. Gunderson, K.L., Steemers, F.J., Lee, G., Mendoza, L.G., Chee, M.S., A genome-wide scalable SNP genotyping assay using microarray technology. Nat. Genet. 37 (2005), 549–554.
37. Guo, S., Diep, D., Plongthongkum, N., Fung, H.-L., Zhang, K., Zhang, K., Identification of methylation haplotype blocks aids in deconvolution of heterogeneous tissue samples and tumor tissue-of-origin mapping from plasma DNA. Nat. Genet. 49 (2017), 635–642.
38. Haque, I.S., Elemento, O., Challenges in Using ctDNA to Achieve Early Detection of Cancer. bioRxiv, 2017, 10.1101/237578.
39. Herper, M. (2018). A Gene Therapy Appears To Replace Missing Protein In Muscular Dystrophy Patients. Forbes, June 19, 2018. https://www.forbes.com/sites/matthewherper/2018/06/19/a-gene-therapy-appears-to-replace-missing-protein-in-muscular-dystrophy-patients/#55e0ddfc5225.
40. Hoischen, A., van Bon, B.W.M., Gilissen, C., Arts, P., van Lier, B., Steehouwer, M., de Vries, P., de Reuver, R., Wieskamp, N., Mortier, G., et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nat. Genet. 42 (2010), 483–485.
41. Hosseini, H., Obradović M.M.S., Hoffmann, M., Harper, K.L., Sosa, M.S., Werner-Klein, M., Nanduri, L.K., Werno, C., Ehrl, C., Maneck, M., et al. Early dissemination seeds metastasis in breast cancer. Nature 540 (2016), 552–558.
42. Hou, Y., Fan, W., Yan, L., Li, R., Lian, Y., Huang, J., Li, J., Xu, L., Tang, F., Xie, X.S., Qiao, J., Genome analyses of single human oocytes. Cell 155 (2013), 1492–1506.
43. Hütter, G., Nowak, D., Mossner, M., Ganepola, S., Müssig, A., Allers, K., Schneider, T., Hofmann, J., Kücherer, C., Blau, O., et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360 (2009), 692–698.
44. International HapMap Consortium. A haplotype map of the human genome. Nature 437 (2005), 1299–1320.
45. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 431 (2004), 931–945.
46. Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E., et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515 (2014), 216–221.
47. Juneau, K., Bogard, P.E., Huang, S., Mohseni, M., Wang, E.T., Ryvkin, P., Kingsley, C., Struble, C.A., Oliphant, A., Zahn, J.M., Microarray-based cell-free DNA analysis improves noninvasive prenatal testing. Fetal Diagn. Ther. 36 (2014), 282–286.
48. Kalia, S.S., Adelman, K., Bale, S.J., Chung, W.K., Eng, C., Evans, J.P., Herman, G.E., Hufnagel, S.B., Klein, T.E., Korf, B.R., et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet. Med. 19 (2017), 249–255.
49. Khera, A.V., Chaffin, M., Aragam, K.G., Haas, M.E., Roselli, C., Choi, S.H., Natarajan, P., Lander, E.S., Lubitz, S.A., Ellinor, P.T., Kathiresan, S., Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50 (2018), 1219–1224.
50. Kitzman, J.O., Snyder, M.W., Ventura, M., Lewis, A.P., Qiu, R., Simmons, L.E., Gammill, H.S., Rubens, C.E., Santillan, D.A., Murray, J.C., et al. Noninvasive Whole-Genome Sequencing of a Human Fetus. Sci. Transl. Med., 4, 2012, 137ra76.
51. Kolata, G., Wee, S.-L., and Belluck, P. (2018). Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies. The New York Times, November 26, 2018. https://www.nytimes.com/2018/11/26/health/gene-editing-babies-china.html.
52. Kumar, A., Ryan, A., Kitzman, J.O., Wemmer, N., Snyder, M.W., Sigurjonsson, S., Lee, C., Banjevic, M., Zarutskie, P.W., Lewis, A.P., et al. Whole genome prediction for preimplantation genetic diagnosis. Genome Med., 7, 2015, 35.
53. Lawrence, M.S., Stojanov, P., Mermel, C.H., Robinson, J.T., Garraway, L.A., Golub, T.R., Meyerson, M., Gabriel, S.B., Lander, E.S., Getz, G., Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505 (2014), 495–501.
54. Leon, S.A., Shapiro, B., Sklaroff, D.M., Yaros, M.J., Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res. 37 (1977), 646–650.
55. Litterman, N.K., Rhee, M., Swinney, D.C., Ekins, S., Collaboration for rare disease drug discovery research. F1000Res., 3, 2014, 261.
56. Liu, S., Huang, S., Chen, F., Zhao, L., Yuan, Y., Francis, S.S., Fang, L., Li, Z., Lin, L., Liu, R., et al. Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History. Cell 175 (2018), 347–359.e14.
57. Lo, Y.M., Corbetta, N., Chamberlain, P.F., Rai, V., Sargent, I.L., Redman, C.W., Wainscoat, J.S., Presence of fetal DNA in maternal plasma and serum. Lancet 350 (1997), 485–487.
58. Lynch, T.J., Bell, D.W., Sordella, R., Gurubhagavatula, S., Okimoto, R.A., Brannigan, B.W., Harris, P.L., Haserlat, S.M., Supko, J.G., Haluska, F.G., et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350 (2004), 2129–2139.
59. Mandel, P., Metais, P., Les acides nucléiques du plasma sanguin chez l'homme. C. R. Seances Soc. Biol. Fil. 142 (1948), 241–243.
60. Manolio, T.A., Collins, F.S., Cox, N.J., Goldstein, D.B., Hindorff, L.A., Hunter, D.J., McCarthy, M.I., Ramos, E.M., Cardon, L.R., Chakravarti, A., et al. Finding the missing heritability of complex diseases. Nature 461 (2009), 747–753.
61. Margulies, M., Egholm, M., Altman, W.E., Attiya, S., Bader, J.S., Bemben, L.A., Berka, J., Braverman, M.S., Chen, Y.-J., Chen, Z., et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437 (2005), 376–380.
62. McCandless, S.E., Brunger, J.W., Cassidy, S.B., The burden of genetic disease on inpatient care in a children's hospital. Am. J. Hum. Genet. 74 (2004), 121–127.
63. Meng, L., Pammi, M., Saronwala, A., Magoulas, P., Ghazi, A.R., Vetrini, F., Zhang, J., He, W., Dharmadhikari, A.V., Qu, C., et al. Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. JAMA Pediatr., 171, 2017, e173438.
64. Motsinger-Reif, A.A., Jorgenson, E., Relling, M.V., Kroetz, D.L., Weinshilboum, R., Cox, N.J., Roden, D.M., Genome-wide association studies in pharmacogenomics: successes and lessons. Pharmacogenet. Genomics 23 (2013), 383–394.
65. Mumbach, M.R., Rubin, A.J., Flynn, R.A., Dai, C., Khavari, P.A., Greenleaf, W.J., Chang, H.Y., HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13 (2016), 919–922.
66. Nelson, M.R., Tipney, H., Painter, J.L., Shen, J., Nicoletti, P., Shen, Y., Floratos, A., Sham, P.C., Li, M.J., Wang, J., et al. The support of human genetic evidence for approved drug indications. Nat. Genet. 47 (2015), 856–860.
67. Ng, S.B., Turner, E.H., Robertson, P.D., Flygare, S.D., Bigham, A.W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E.E., et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461 (2009), 272–276.
68. Niemi, M.E.K., Martin, H.C., Rice, D.L., Gallone, G., Gordon, S., Kelemen, M., McAloney, K., McRae, J., Radford, E.J., Yu, S., et al. Common genetic variants contribute to risk of rare severe neurodevelopmental disorders. Nature 562 (2018), 268–271.
69. Noone, A.M., Howlader, N., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., Lewis, D.R., et al. (2018). SEER Cancer Statistics Review, 1975–2015. National Cancer Institute, last updated September 10, 2018. https://seer.cancer.gov/csr/1975_2015/.
70. Norton, M.E., Wapner, R.J., Cell-free DNA Analysis for Noninvasive Examination of Trisomy. N. Engl. J. Med., 373, 2015, 2582.
71. Ott, P.A., Hu, Z., Keskin, D.B., Shukla, S.A., Sun, J., Bozym, D.J., Zhang, W., Luoma, A., Giobbie-Hurder, A., Peter, L., et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547 (2017), 217–221.
72. Ozaki, K., Ohnishi, Y., Iida, A., Sekine, A., Yamada, R., Tsunoda, T., Sato, H., Sato, H., Hori, M., Nakamura, Y., Tanaka, T., Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat. Genet. 32 (2002), 650–654.
73. Paez, J.G., Jänne, P.A., Lee, J.C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F.J., Lindeman, N., Boggon, T.J., et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304 (2004), 1497–1500.
74. Perdigoto, C., Mutations: Dawn of the Human Knockout Project. Nat. Rev. Genet. 18 (2017), 328–329.
75. Radovich, M., Kiel, P.J., Nance, S.M., Niland, E.E., Parsley, M.E., Ferguson, M.E., Jiang, G., Ammakkanavar, N.R., Einhorn, L.H., Cheng, L., et al. Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers. Oncotarget 7 (2016), 56491–56500.
76. Ramsey, B.W., Davies, J., McElvaney, N.G., Tullis, E., Bell, S.C., Dřevínek, P., Griese, M., McKone, E.F., Wainwright, C.E., Konstan, M.W., et al., VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N. Engl. J. Med. 365 (2011), 1663–1672.
77. Rangarajan, S., Walsh, L., Lester, W., Perry, D., Madan, B., Laffan, M., Yu, H., Vettermann, C., Pierce, G.F., Wong, W.Y., Pasi, K.J., AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. N. Engl. J. Med. 377 (2017), 2519–2530.
78. Ribeil, J.-A., Hacein-Bey-Abina, S., Payen, E., Magnani, A., Semeraro, M., Magrin, E., Caccavelli, L., Neven, B., Bourget, P., El Nemer, W., et al. Gene Therapy in a Patient with Sickle Cell Disease. N. Engl. J. Med. 376 (2017), 848–855.
79. Risch, N., Merikangas, K., The future of genetic studies of complex human diseases. Science 273 (1996), 1516–1517.
80. Russell, R. (2018). Polygenic Risk Scores: Combining Thousands of Genetic Variants to Predict Disease. Reinsurance Group of America, Inc., September 10, 2018. https://www.rgare.com/knowledge-center/media/articles/polygenic-risk-scores-combining-thousands-of-genetic-variants-to-predict-disease.
81. Sahin, U., Derhovanessian, E., Miller, M., Kloke, B.-P., Simon, P., Löwer, M., Bukur, V., Tadmor, A.D., Luxemburger, U., Schrörs, B., et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547 (2017), 222–226.
82. Saunders, C.J., Miller, N.A., Soden, S.E., Dinwiddie, D.L., Noll, A., Alnadi, N.A., Andraws, N., Patterson, M.L., Krivohlavek, L.A., Fellis, J., et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci. Transl. Med., 4, 2012, 154ra135.
83. Shendure, J., Lieberman Aiden, E., The expanding scope of DNA sequencing. Nat. Biotechnol. 30 (2012), 1084–1094.
84. Shendure, J., Porreca, G.J., Reppas, N.B., Lin, X., McCutcheon, J.P., Rosenbaum, A.M., Wang, M.D., Zhang, K., Mitra, R.D., Church, G.M., Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309 (2005), 1728–1732.
85. Shendure, J., Balasubramanian, S., Church, G.M., Gilbert, W., Rogers, J., Schloss, J.A., Waterston, R.H., DNA sequencing at 40: past, present and future. Nature 550 (2017), 345–353.
86. Snyder, M.W., Kircher, M., Hill, A.J., Daza, R.M., Shendure, J., Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin. Cell 164 (2016), 57–68.
87. Sparks, A.B., Wang, E.T., Struble, C.A., Barrett, W., Stokowski, R., McBride, C., Zahn, J., Lee, K., Shen, N., Doshi, J., et al. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat. Diagn. 32 (2012), 3–9.
88. Srinivasan, A., Bianchi, D.W., Huang, H., Sehnert, A.J., Rava, R.P., Noninvasive detection of fetal subchromosome abnormalities via deep sequencing of maternal plasma. Am. J. Hum. Genet. 92 (2013), 167–176.
89. Starita, L.M., Ahituv, N., Dunham, M.J., Kitzman, J.O., Roth, F.P., Seelig, G., Shendure, J., Fowler, D.M., Variant Interpretation: Functional Assays to the Rescue. Am. J. Hum. Genet. 101 (2017), 315–325.
90. Stossel, T.P., The discovery of statins. Cell 134 (2008), 903–905.
91. Stroun, M., Anker, P., Lyautey, J., Lederrey, C., Maurice, P.A., Isolation and characterization of DNA from the plasma of cancer patients. Eur. J. Cancer Clin. Oncol. 23 (1987), 707–712.
92. Sun, K., Jiang, P., Chan, K.C.A., Wong, J., Cheng, Y.K.Y., Liang, R.H.S., Chan, W.-K., Ma, E.S.K., Chan, S.L., Cheng, S.H., et al. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments. Proc. Natl. Acad. Sci. USA 112 (2015), E5503–E5512.
93. Tebas, P., Stein, D., Tang, W.W., Frank, I., Wang, S.Q., Lee, G., Spratt, S.K., Surosky, R.T., Giedlin, M.A., Nichol, G., et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370 (2014), 901–910.
94. Topol, E.J., Individualized medicine from prewomb to tomb. Cell 157 (2014), 241–253.
95. Visscher, P.M., Wray, N.R., Zhang, Q., Sklar, P., McCarthy, M.I., Brown, M.A., Yang, J., 10 Years of GWAS Discovery: Biology, Function, and Translation. Am. J. Hum. Genet. 101 (2017), 5–22.
96. Voight, B.F., Peloso, G.M., Orho-Melander, M., Frikke-Schmidt, R., Barbalic, M., Jensen, M.K., Hindy, G., Hólm, H., Ding, E.L., Johnson, T., et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 380 (2012), 572–580.
97. Wapner, R.J., Babiarz, J.E., Levy, B., Stosic, M., Zimmermann, B., Sigurjonsson, S., Wayham, N., Ryan, A., Banjevic, M., Lacroute, P., et al. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am. J. Obstet. Gynecol. 212 (2015), 332.e1–332.e9.
98. Weiner, D.J., Wigdor, E.M., Ripke, S., Walters, R.K., Kosmicki, J.A., Grove, J., Samocha, K.E., Goldstein, J., Okbay, A., Bybjerg-Gauholm, J., et al. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat Genet. 49 (2017), 978–985.
99. Wheler, J.J., Yelensky, R., Stephen, B., Hong, D.S., Zinner, R., Subbiah, V., Fu, S., Karp, D.D., Falchook, G.S., Naing, A., et al. Prospective study comparing outcomes in patients with advanced malignancies on molecular alteration-matched versus non-matched therapy. J Clin Oncol., 33, 2015, 11019.
100. Willer, C.J., Schmidt, E.M., Sengupta, S., Peloso, G.M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M.L., Mora, S., et al., Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 45 (2013), 1274–1283.
101. Willig, L.K., Petrikin, J.E., Smith, L.D., Saunders, C.J., Thiffault, I., Miller, N.A., Soden, S.E., Cakici, J.A., Herd, S.M., Twist, G., et al. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir. Med. 3 (2015), 377–387.
102. Wilson, C., Exclusive: A new test can predict IVF embryos’ risk of having a low IQ. New Scientist., 2018 November 15, 2018 https://www.newscientist.com/article/mg24032041-900-exclusive-a-new-test-can-predict-ivf-embryos-risk-of-having-a-low-iq/.
103. Wray, N.R., Yang, J., Hayes, B.J., Price, A.L., Goddard, M.E., Visscher, P.M., Pitfalls of predicting complex traits from SNPs. Nat. Rev. Genet. 14 (2013), 507–515.
104. Yang, J., Benyamin, B., McEvoy, B.P., Gordon, S., Henders, A.K., Nyholt, D.R., Madden, P.A., Heath, A.C., Martin, N.G., Montgomery, G.W., et al. Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 42 (2010), 565–569.
105. Yang, Y., Muzny, D.M., Reid, J.G., Bainbridge, M.N., Willis, A., Ward, P.A., Braxton, A., Beuten, J., Xia, F., Niu, Z., et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N. Engl. J. Med. 369 (2013), 1502–1511.
106. Yuzuki, D. (2015). What is Non-Invasive Prenatal Testing (NIPT)? Genomic Precision, SeraCare blog, November 17, 2015. https://blog.seracare.com/home/tabid/294/artmid/989/articleid/23/what-is-non-invasive-prenatal-testing-nipt.aspx.
107. Zimmermann, B., Hill, M., Gemelos, G., Demko, Z., Banjevic, M., Baner, J., Ryan, A., Sigurjonsson, S., Chopra, N., Dodd, M., et al. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat. Diagn. 32 (2012), 1233–1241.