Next-Gen 101: Video Tutorial on Conducting Whole-Exome Sequencing Research

Next-Gen 101: Video Tutorial on Conducting Whole-Exome Sequencing Research

Agenda

Welcome and Introduction to the Course Video | Slides	Eric Green, M.D., Ph.D. Director, National Human Genome Research Institute
Whole-Exome Sequencing: Technical Details Video | Slides	James Mullikin, Ph.D. Director, NIH Intramural Sequencing Center
Variant Annotation and Viewing Exome Sequencing Data Video | Slides	Jamie K. Teer, Ph.D. Genetic Disease Research Branch, NHGRI
Filtering Strategies for Identifying Germline Variants that Cause Disease Video | Slides	Leslie Biesecker, M.D. Chief, Genetic Disease Research Branch, NHGRI
Whole-Exome Sequencing to Identify Somatic Variants in Cancer Video | Slides	Yardena Samuels, Ph.D. Cancer Genetics Branch, NHGRI
Morning Speakers Q&A Panel Video
Integrating Exome Variants with Other Genomic Data and Functional Annotations Video | Slides	David Adams, M.D., Ph.D. Medical Genetics Branch, NHGRI
Secondary or Incidental Findings from Exome Sequence Data Video | Slides	Jennifer Johnston, Ph.D. Genetic Disease Research Branch, NHGRI
Ethics and IRB Issues Related to Whole-Exome Sequencing Video | Slides	Sara Hull, Ph.D. NHGRI and Department of Bioethics, NIH Clinical Center
Informed Consent and Returning Results in Whole-Exome Sequencing Protocols Video | Slides	Julie Sapp, Sc.M., C.G.C. Genetic Disease Research Branch, NHGRI
Afternoon Speakers Q&A Panel Video

Citations for the presentations for Next-Gen 101:

James Mullikin, Ph.D.

Teer JK, Mullikin JC. Exome sequencing: the sweet spot before whole genomes. Hum Mol Genet, 19(R2):R145-51. 2010. [PubMed]

Jaime Teer, Ph.D.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R; 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics, 25(16):2078-9. 2009. [PubMed]

Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP.Integrative genomics viewer. Nat Biotechnol, Jan;29(1):24-6. 2011. [PubMed]

Leslie Biesecker, M.D.

Johnston JJ, Teer JK, Cherukuri PF, Hansen NF, Loftus SK, NIH intramural sequencing center, Chong K, Mullikin JF, Biesecker LG. Massively parallel sequencing of exons on the X chromosome identify RBM10 as the gene that causes a syndromic form of cleft palate. Am J Hum Genet, 86:743-748. 2010. [PubMed]

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, O'Brien K, Hauser NS, Sapp JC, NISC, Barshop BA, Berry S, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Nyhan WL, Biesecker LG, Venditti CP. Whole exome sequencing identifies mutations in ACSF3 as the cause of combined malonic and methylmalonic aciduria. Nat Genet, 43:883-886. 2011. [PubMed]

Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, Le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, Le Caignec C. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat Genet, 43:306-308. 2011. [PubMed]

Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet, 43:303-305. 2011. [PubMed]

Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet, 42:790-793.2010. [PubMed]

Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff M, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O'Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC for the NISC Comparative Sequencing Program, Biesecker LG. A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome. New Engl J Med, 365:611-619. 2011. [PubMed]

Yardena Samuels, Ph.D.

Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S; NISC Comparative Sequencing Program, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet, (5):442-6. 2011. [PubMed]

Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in pancreatic cancer revealed by global genomic analyses. Science, 321(5897):1801-6. 2008. [PubMed]

Jennifer Johnston, Ph.D.

Bell, C.J., Dinwiddie, D.L., Miller, N.A., Hateley, S.L., Ganusova, E.E., Mudge, J., Langley, R.J., Zhang, L., Lee, C.C., Schilkey, F.D., et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med, 3;65ra64. 2011. [PubMed]

Lindor, N.M., McMaster, M.L., Lindor, C.J., and Greene, M.H. Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr, 1-93. 2008. [PubMed]

Fabsitz, R.R., McGuire, A., Sharp, R.R., Puggal, M., Beskow, L.M., Biesecker, L.G., Bookman, E., Burke, W., Burchard, E.G., Church, G., et al. 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;574-580. 2010. [PubMed]

Plon, S.E., Eccles, D.M., Easton, D., Foulkes, W.D., Genuardi, M., Greenblatt, M.S., Hogervorst, F.B., Hoogerbrugge, N., Spurdle, A.B., and Tavtigian, S.V. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat, 29, 1282-1291. 2008. [PubMed]

Sara Hull, Ph.D.

Beskow LM, Burke W. Offering individual genetic research results: context matters. Sci Transl Med, 2(38):38cm20. 2010. [PubMed]

Bookman EB, Langehorne AA, Eckfeldt JH, Glass KC, Jarvik GP, Klag M, Koski G, Motulsky A, Wilfond B, Manolio TA, Fabsitz RR, Luepker RV. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am J Med Genet A, 140:1033-1040. 2006. [PubMed]

National Heart, Lung, and Blood Institute working group, Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM, Biesecker LG, Bookman E, Burke W, Burchard EG, Church G, Clayton EW, Eckfeldt JH, Fernandez CV, Fisher R, Fullerton SM, Gabriel S, Gachupin F, James C, Jarvik GP, Kittles R, Leib JR, O'Donnell C, O'Rourke PP, Rodriguez LL, Schully SD, Shuldiner AR, Sze RK, Thakuria JV, Wolf SM, Burke GL. 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(6):574-80. 2010. [PubMed]

Ravitsky V, Wilfond BS. Disclosing individual genetic results to research participants. Am J Bioeth, 6(6):8-17. 2006. [PubMed]

Rothstein MA. Tiered disclosure options promote the autonomy and well-being of research subjects. Am J Bioeth, 6(6):20-1. 2006. [PubMed]

Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics, 36(2):219-48, 2008. [PubMed]

Julie Sapp, Sc.M., C.G.C.

Facio FM, Brooks S, Loewenstein J, Green S, Biesecker LG, Biesecker BB. Motivators for participation in a whole-genome sequencing study: implications for translational genomics research. Eur J Hum Genet, 07/6/2011. [PubMed]

Bredenoord AL, Onland-Moret NC, Van Delden JJ. Feedback of individual genetic results to research participants: in favor of a qualified disclosure policy. Hum Mutat, 32(8):861-7. 2011. [PubMed]