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1. Peer MD Coaching Partnership Outcomes Between an NCI-designated Cancer Center Genetics Service and a Community Cancer Network Hospital

Author

Santos, LG, primary, Buzdnitskaya, T, additional, Rolf, BA, additional, Sienko, M, additional, Ruiz-Bonilla, J, additional, Shah, B, additional, Jewell, P, additional, Jensen, L, additional, Horike-Pyne, M, additional, Elrod, J, additional, Crews, JR, additional, Laurino, MY, additional, Weeks, K, additional, and Dubard-Gault, ME, additional

Published
2023
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2. Human genome meeting 2016

Author

Srivastava, A., Wang, Y., Huang, R., Skinner, C., Thompson, T., Pollard, L., Wood, T., Luo, F., Stevenson, R., Polimanti, R., Gelernter, J., Lin, X., Lim, I., Wu, Y., Teh, A., Chen, L., Aris, I., Soh, S., Tint, M., MacIsaac, J., Yap, F., Kwek, K., Saw, S., Kobor, M., Meaney, M., Godfrey, K., Chong, Y., Holbrook, J., Lee, Y., Gluckman, P., Karnani, N., Kapoor, A., Lee, D., Chakravarti, A., Maercker, C., Graf, F., Boutros, M., Stamoulis, G., Santoni, F., Makrythanasis, P., Letourneau, A., Guipponi, M., Panousis, N., Garieri, M., Ribaux, P., Falconnet, E., Borel, C., Antonarakis, S., Kumar, S., Curran, J., Blangero, J., Chatterjee, S., Kapoor, A., Akiyama, J., Auer, D., Berrios, C., Pennacchio, L., Chakravarti, A., Donti, T., Cappuccio, G., Miller, M., Atwal, P., Kennedy, A., Cardon, A., Bacino, C., Emrick, L., Hertecant, J., Baumer, F., Porter, B., Bainbridge, M., Bonnen, P., Graham, B., Sutton, R., Sun, Q., Elsea, S., Hu, Z., Wang, P., Zhu, Y., Zhao, J., Xiong, M., Bennett, David, Hidalgo-Miranda, A., Romero-Cordoba, S., Rodriguez-Cuevas, S., Rebollar-Vega, R., Tagliabue, E., Iorio, M., D’Ippolito, E., Baroni, S., Kaczkowski, B., Tanaka, Y., Kawaji, H., Sandelin, A., Andersson, R., Itoh, M., Lassmann, T., Hayashizaki, Y., Carninci, P., Forrest, A., Semple, C., Rosenthal, E., Shirts, B., Amendola, L., Gallego, C., Horike-Pyne, M., Burt, A., Robertson, P., Beyers, P., Nefcy, C., Veenstra, D., Hisama, F., Bennett, R., Dorschner, M., Nickerson, D., Smith, J., Patterson, K., Crosslin, D., Nassir, R., Zubair, N., Harrison, T., Peters, U., Jarvik, G., Menghi, F., Inaki, K., Woo, X., Kumar, P., Grzeda, K., Malhotra, A., Kim, H., Ucar, D., Shreckengast, P., Karuturi, K., Keck, J., Chuang, J., Liu, E., Ji, B., Tyler, A., Ananda, G., Carter, G., Nikbakht, H., Montagne, M., Zeinieh, M., Harutyunyan, A., Mcconechy, M., Jabado, N., Lavigne, P., Majewski, J., Goldstein, J., Overman, M., Varadhachary, G., Shroff, R., Wolff, R., Javle, M., Futreal, A., Fogelman, D., Bravo, L., Fajardo, W., Gomez, H., Castaneda, C., Rolfo, C., Pinto, J., Akdemir, K., Chin, L., Futreal, A., Patterson, S., Statz, C., Mockus, S., Nikolaev, S., Bonilla, X., Parmentier, L., King, B., Bezrukov, F., Kaya, G., Zoete, V., Seplyarskiy, V., Sharpe, H., McKee, T., Letourneau, A., Ribaux, P., Popadin, K., Basset-Seguin, N., Chaabene, R., Santoni, F., Andrianova, M., Guipponi, M., Garieri, M., Verdan, C., Grosdemange, K., Sumara, O., Eilers, M., Aifantis, I., Michielin, O., de Sauvage, F., Antonarakis, S., Likhitrattanapisal, S., Lincoln, S., Kurian, A., Desmond, A., Yang, S., Kobayashi, Y., Ford, J., Ellisen, L., Peters, T., Alvarez, K., Hollingsworth, E., Lopez-Terrada, D., Hastie, A., Dzakula, Z., Pang, A., Lam, E., Anantharaman, T., Saghbini, M., Cao, H., Gonzaga-Jauregui, C., Ma, L., King, A., Rosenzweig, E., Krishnan, U., Reid, J., Overton, J., Dewey, F., Chung, W., Small, K., DeLuca, A., Cremers, F., Lewis, R., Puech, V., Bakall, B., Silva-Garcia, R., Rohrschneider, K., Leys, M., Shaya, F., Stone, E., Sobreira, N., Schiettecatte, F., Ling, H., Pugh, E., Witmer, D., Hetrick, K., Zhang, P., Doheny, K., Valle, D., Hamosh, A., Jhangiani, S., Akdemir, Z., Bainbridge, M., Charng, W., Wiszniewski, W., Gambin, T., Karaca, E., Bayram, Y., Eldomery, M., Posey, J., Doddapaneni, H., Hu, J., Sutton, V., Muzny, D., Boerwinkle, E., Valle, D., Lupski, J., Gibbs, R., Shekar, S., Salerno, W., English, A., Mangubat, A., Bruestle, J., Thorogood, A., Knoppers, B., Takahashi, H., Nitta, K., Kozhuharova, A., Suzuki, A., Sharma, H., Cotella, D., Santoro, C., Zucchelli, S., Gustincich, S., Carninci, P., Mulvihill, J., Baynam, G., Gahl, W., Groft, S., Kosaki, K., Lasko, P., Melegh, B., Taruscio, D., Ghosh, R., Plon, S., Scherer, S., Qin, X., Sanghvi, R., Walker, K., Chiang, T., Muzny, D., Wang, L., Black, J., Boerwinkle, E., Weinshilboum, R., Gibbs, R., Karpinets, T., Calderone, T., Wani, K., Yu, X., Creasy, C., Haymaker, C., Forget, M., Nanda, V., Roszik, J., Wargo, J., Haydu, L., Song, X., Lazar, A., Gershenwald, J., Davies, M., Bernatchez, C., Zhang, J., Futreal, A., Woodman, S., Chesler, E., Reynolds, T., Bubier, J., Phillips, C., Langston, M., Baker, E., Xiong, M., Ma, L., Lin, N., Amos, C., Lin, N., Wang, P., Zhu, Y., Zhao, J., Calhoun, V., Xiong, M., Dobretsberger, O., Egger, M., Leimgruber, F., Sadedin, S., Oshlack, A., Antonio, V., Ono, N., Ahmed, Z., Bolisetty, M., Zeeshan, S., Anguiano, E., Ucar, D., Sarkar, A., Nandineni, M., Zeng, C., Shao, J., Cao, H., Hastie, A., Pang, A., Lam, E., Liang, T., Pham, K., Saghbini, M., Dzakula, Z., Chee-Wei, Y., Dongsheng, L., Lai-Ping, W., Lian, D., Hee, R., Yunus, Y., Aghakhanian, F., Mokhtar, S., Lok-Yung, C., Bhak, J., Phipps, M., Shuhua, X., Yik-Ying, T., Kumar, V., Boon-Peng, H., Campbell, I., Young, M., James, P., Rain, M., Mohammad, G., Kukreti, R., Pasha, Q., Akilzhanova, A., Guelly, C., Abilova, Z., Rakhimova, S., Akhmetova, A., Kairov, U., Trajanoski, S., Zhumadilov, Z., Bekbossynova, M., Schumacher, C., Sandhu, S., Harkins, T., Makarov, V., Doddapaneni, H., Glenn, R., Momin, Z., Dilrukshi, B., Chao, H., Meng, Q., Gudenkauf, B., Kshitij, R., Jayaseelan, J., Nessner, C., Lee, S., Blankenberg, K., Lewis, L., Hu, J., Han, Y., Dinh, H., Jireh, S., Walker, K., Boerwinkle, E., Muzny, D., Gibbs, R., Hu, J., Walker, K., Buhay, C., Liu, X., Wang, Q., Sanghvi, R., Doddapaneni, H., Ding, Y., Veeraraghavan, N., Yang, Y., Boerwinkle, E., Beaudet, A., Eng, C., Muzny, D., Gibbs, R., Worley, K., Liu, Y., Hughes, D., Murali, S., Harris, R., English, A., Qin, X., Hampton, O., Larsen, P., Beck, C., Han, Y., Wang, M., Doddapaneni, H., Kovar, C., Salerno, W., Yoder, A., Richards, S., Rogers, J., Lupski, J., Muzny, D., Gibbs, R., Meng, Q., Bainbridge, M., Wang, M., Doddapaneni, H., Han, Y., Muzny, D., Gibbs, R., Harris, R., Raveenedran, M., Xue, C., Dahdouli, M., Cox, L., Fan, G., Ferguson, B., Hovarth, J., Johnson, Z., Kanthaswamy, S., Kubisch, M., Platt, M., Smith, D., Vallender, E., Wiseman, R., Liu, X., Below, J., Muzny, D., Gibbs, R., Yu, F., Rogers, J., Lin, J., Zhang, Y., Ouyang, Z., Moore, A., Wang, Z., Hofmann, J., Purdue, M., Stolzenberg-Solomon, R., Weinstein, S., Albanes, D., Liu, C., Cheng, W., Lin, T., Lan, Q., Rothman, N., Berndt, S., Chen, E., Bahrami, H., Khoshzaban, A., Keshal, S., Bahrami, H., Khoshzaban, A., Keshal, S., Alharbi, K., Zhalbinova, M., Akilzhanova, A., Rakhimova, S., Bekbosynova, M., Myrzakhmetova, S., Matar, M., Mili, N., Molinari, R., Ma, Y., Guerrier, S., Elhawary, N., Tayeb, M., Bogari, N., Qotb, N., McClymont, S., Hook, P., Goff, L., McCallion, A., Kong, Y., Charette, J., Hicks, W., Naggert, J., Zhao, L., Nishina, P., Edrees, B., Athar, M., Al-Allaf, F., Taher, M., Khan, W., Bouazzaoui, A., Harbi, N., Safar, R., Al-Edressi, H., Anazi, A., Altayeb, N., Ahmed, M., Alansary, K., Abduljaleel, Z., Kratz, A., Beguin, P., Poulain, S., Kaneko, M., Takahiko, C., Matsunaga, A., Kato, S., Suzuki, A., Bertin, N., Lassmann, T., Vigot, R., Carninci, P., Plessy, C., Launey, T., Graur, D., Lee, D., Kapoor, A., Chakravarti, A., Friis-Nielsen, J., Izarzugaza, J., Brunak, S., Chakraborty, A., Basak, J., Mukhopadhyay, A., Soibam, B., Das, D., Biswas, N., Das, S., Sarkar, S., Maitra, A., Panda, C., Majumder, P., Morsy, H., Gaballah, A., Samir, M., Shamseya, M., Mahrous, H., Ghazal, A., Arafat, W., Hashish, M., Gruber, J., Jaeger, N., Snyder, M., Patel, K., Bowman, S., Davis, T., Kraushaar, D., Emerman, A., Russello, S., Henig, N., Hendrickson, C., Zhang, K., Rodriguez-Dorantes, M., Cruz-Hernandez, C., Garcia-Tobilla, C., Solorzano-Rosales, S., Jäger, N., Chen, J., Haile, R., Hitchins, M., Brooks, J., Snyder, M., Jiménez-Morales, S., Ramírez, M., Nuñez, J., Bekker, V., Leal, Y., Jiménez, E., Medina, A., Hidalgo, A., Mejía, J., Halytskiy, V., Naggert, J., Collin, G., DeMauro, K., Hanusek, R., Nishina, P., Belhassa, K., Belhassan, K., Bouguenouch, L., Samri, I., Sayel, H., moufid, FZ., El Bouchikhi, I., Trhanint, S., Hamdaoui, H., Elotmani, I., Khtiri, I., Kettani, O., Quibibo, L., Ahagoud, M., Abbassi, M., Ouldim, K., Marusin, A., Kornetov, A., Swarovskaya, M., Vagaiceva, K., Stepanov, V., De La Paz, E., Sy, R., Nevado, J., Reganit, P., Santos, L., Magno, J., Punzalan, F., Ona, D., Llanes, E., Santos-Cortes, R., Tiongco, R., Aherrera, J., Abrahan, L., Pagauitan-Alan, P., Morelli, K., Domire, J., Pyne, N., Harper, S., Burgess, R., Zhalbinova, M., Akilzhanova, A., Rakhimova, S., Bekbosynova, M., Myrzakhmetova, S., Gari, M., Dallol, A., Alsehli, H., Gari, A., Gari, M., Abuzenadah, A., Thomas, M., Sukhai, M., Garg, S., Misyura, M., Zhang, T., Schuh, A., Stockley, T., Kamel-Reid, S., Sherry, S., Xiao, C., Slotta, D., Rodarmer, K., Feolo, M., Kimelman, M., Godynskiy, G., O’Sullivan, C., Yaschenko, E., Xiao, C., Yaschenko, E., Sherry, S., Rangel-Escareño, C., Rueda-Zarate, H., Tayubi, I., Mohammed, R., Ahmed, I., Ahmed, T., Seth, S., Amin, S., Song, X., Mao, X., Sun, H., Verhaak, R., Futreal, A., Zhang, J., Whiite, S., Chiang, T., English, A., Farek, J., Kahn, Z., Salerno, W., Veeraraghavan, N., Boerwinkle, E., Gibbs, R., Kasukawa, T., Lizio, M., Harshbarger, J., Hisashi, S., Severin, J., Imad, A., Sahin, S., Freeman, T., Baillie, K., Sandelin, A., Carninci, P., Forrest, A., Kawaji, H., Salerno, W., English, A., Shekar, S., Mangubat, A., Bruestle, J., Boerwinkle, E., Gibbs, R., Salem, A., Ali, M., Ibrahim, A., Ibrahim, M., Barrera, H., Garza, L., Torres, J., Barajas, V., Ulloa-Aguirre, A., Kershenobich, D., Mortaji, Shahroj, Guizar, Pedro, Loera, Eliezer, Moreno, Karen, De León, Adriana, Monsiváis, Daniela, Gómez, Jackeline, Cardiel, Raquel, Fernandez-Lopez, J., Bonifaz-Peña, V., Rangel-Escareño, C., Hidalgo-Miranda, A., Contreras, A., Polfus, L., Wang, X., Philip, V., Carter, G., Abuzenadah, A., Gari, M., Turki, R., Dallol, A., Uyar, A., Kaygun, A., Zaman, S., Marquez, E., George, J., Ucar, D., Hendrickson, C., Emerman, A., Kraushaar, D., Bowman, S., Henig, N., Davis, T., Russello, S., Patel, K., Starr, D., Baird, M., Kirkpatrick, B., Sheets, K., Nitsche, R., Prieto-Lafuente, L., Landrum, M., Lee, J., Rubinstein, W., Maglott, D., Thavanati, P., de Dios, A., Hernandez, R., Aldrate, M., Mejia, M., Kanala, K., Abduljaleel, Z., Khan, W., Al-Allaf, F., Athar, M., Taher, M., Shahzad, N., Bouazzaoui, A., Huber, E., Dan, A., Al-Allaf, F., Herr, W., Sprotte, G., Köstler, J., Hiergeist, A., Gessner, A., Andreesen, R., Holler, E., Al-Allaf, F., Alashwal, A., Abduljaleel, Z., Taher, M., Bouazzaoui, A., Abalkhail, H., Al-Allaf, A., Bamardadh, R., Athar, M., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Al-allaf, F., Mohiuddin, M., Zainularifeen, A., Mohammed, A., Abalkhail, H., Owaidah, T., and Bouazzaoui, A.

Abstract

O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth weight and subsequent postnatal outcomes: findings from GUSTO, an Asian birth cohort X. Lin, I. Y. Lim, Y. Wu, A. L. Teh, L. Chen, I. M. Aris, S. E. Soh, M. T. Tint, J. L. MacIsaac, F. Yap, K. Kwek, S. M. Saw, M. S. Kobor, M. J. Meaney, K. M. Godfrey, Y. S. Chong, J. D. Holbrook, Y. S. Lee, P. D. Gluckman, N. Karnani, GUSTO study group O4 High-throughput identification of specific qt interval modulating enhancers at the SCN5A locus A. Kapoor, D. Lee, A. Chakravarti O5 Identification of extracellular matrix components inducing cancer cell migration in the supernatant of cultivated mesenchymal stem cells C. Maercker, F. Graf, M. Boutros O6 Single cell allele specific expression (ASE) IN T21 and common trisomies: a novel approach to understand DOWN syndrome and other aneuploidies G. Stamoulis, F. Santoni, P. Makrythanasis, A. Letourneau, M. Guipponi, N. Panousis, M. Garieri, P. Ribaux, E. Falconnet, C. Borel, S. E. Antonarakis O7 Role of microRNA in LCL to IPSC reprogramming S. Kumar, J. Curran, J. Blangero O8 Multiple enhancer variants disrupt gene regulatory network in Hirschsprung disease S. Chatterjee, A. Kapoor, J. Akiyama, D. Auer, C. Berrios, L. Pennacchio, A. Chakravarti O9 Metabolomic profiling for the diagnosis of neurometabolic disorders T. R. Donti, G. Cappuccio, M. Miller, P. Atwal, A. Kennedy, A. Cardon, C. Bacino, L. Emrick, J. Hertecant, F. Baumer, B. Porter, M. Bainbridge, P. Bonnen, B. Graham, R. Sutton, Q. Sun, S. Elsea O10 A novel causal methylation network approach to Alzheimer’s disease Z. Hu, P. Wang, Y. Zhu, J. Zhao, M. Xiong, David A Bennett O11 A microRNA signature identifies subtypes of triple-negative breast cancer and reveals MIR-342-3P as regulator of a lactate metabolic pathway A. Hidalgo-Miranda, S. Romero-Cordoba, S. Rodriguez-Cuevas, R. Rebollar-Vega, E. Tagliabue, M. Iorio, E. D’Ippolito, S. Baroni O12 Transcriptome analysis identifies genes, enhancer RNAs and repetitive elements that are recurrently deregulated across multiple cancer types B. Kaczkowski, Y. Tanaka, H. Kawaji, A. Sandelin, R. Andersson, M. Itoh, T. Lassmann, the FANTOM5 consortium, Y. Hayashizaki, P. Carninci, A. R. R. Forrest O13 Elevated mutation and widespread loss of constraint at regulatory and architectural binding sites across 11 tumour types C. A. Semple O14 Exome sequencing provides evidence of pathogenicity for genes implicated in colorectal cancer E. A. Rosenthal, B. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, A. Burt, P. Robertson, P. Beyers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. Dorschner, D. Nickerson, J. Smith, K. Patterson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. Jarvik, NHLBI GO Exome Sequencing Project O15 The tandem duplicator phenotype as a distinct genomic configuration in cancer F. Menghi, K. Inaki, X. Woo, P. Kumar, K. Grzeda, A. Malhotra, H. Kim, D. Ucar, P. Shreckengast, K. Karuturi, J. Keck, J. Chuang, E. T. Liu O16 Modeling genetic interactions associated with molecular subtypes of breast cancer B. Ji, A. Tyler, G. Ananda, G. Carter O17 Recurrent somatic mutation in the MYC associated factor X in brain tumors H. Nikbakht, M. Montagne, M. Zeinieh, A. Harutyunyan, M. Mcconechy, N. Jabado, P. Lavigne, J. Majewski O18 Predictive biomarkers to metastatic pancreatic cancer treatment J. B. Goldstein, M. Overman, G. Varadhachary, R. Shroff, R. Wolff, M. Javle, A. Futreal, D. Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. Puech, B. Bakall, R. Silva-Garcia, K. Rohrschneider, M. Leys, F. S. Shaya, E. Stone O29 PhenoDB and genematcher, solving unsolved whole exome sequencing data N. L. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, D. Valle, A. Hamosh O30 Baylor-Johns Hopkins Center for Mendelian genomics: a four year review S. N. Jhangiani, Z. Coban Akdemir, M. N. Bainbridge, W. Charng, W. Wiszniewski, T. Gambin, E. Karaca, Y. Bayram, M. K. Eldomery, J. Posey, H. Doddapaneni, J. Hu, V. R. Sutton, D. M. Muzny, E. A. Boerwinkle, D. Valle, J. R. Lupski, R. A. Gibbs O31 Using read overlap assembly to accurately identify structural genetic differences in an ashkenazi jewish trio S. Shekar, W. Salerno, A. English, A. Mangubat, J. Bruestle O32 Legal interoperability: a sine qua non for international data sharing A. Thorogood, B. M. Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. Weinshilboum, R. Gibbs O38 Melanoma reprogramming state correlates with response to CTLA-4 blockade in metastatic melanoma T. Karpinets, T. Calderone, K. Wani, X. Yu, C. Creasy, C. Haymaker, M. Forget, V. Nanda, J. Roszik, J. Wargo, L. Haydu, X. Song, A. Lazar, J. Gershenwald, M. Davies, C. Bernatchez, J. Zhang, A. Futreal, S. Woodman O39 Data-driven refinement of complex disease classification from integration of heterogeneous functional genomics data in GeneWeaver E. J. Chesler, T. Reynolds, J. A. Bubier, C. Phillips, M. A. Langston, E. J. Baker O40 A general statistic framework for genome-based disease risk prediction M. Xiong, L. Ma, N. Lin, C. Amos O41 Integrative large-scale causal network analysis of imaging and genomic data and its application in schizophrenia studies N. Lin, P. Wang, Y. Zhu, J. Zhao, V. Calhoun, M. Xiong O42 Big data and NGS data analysis: the cloud to the rescue O. Dobretsberger, M. Egger, F. Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. Gibbs O56 A diploid personal human genome model for better genomes from diverse sequence data K. C. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, X. Qin, O. A. Hampton, P. Larsen, C. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, A. Yoder, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs O57 Development of PacBio long range capture for detection of pathogenic structural variants Q. Meng, M. Bainbridge, M. Wang, H. Doddapaneni, Y. Han, D. Muzny, R. Gibbs O58 Rhesus macaques exhibit more non-synonymous variation but greater impact of purifying selection than humans R. A. Harris, M. Raveenedran, C. Xue, M. Dahdouli, L. Cox, G. Fan, B. Ferguson, J. Hovarth, Z. Johnson, S. Kanthaswamy, M. Kubisch, M. Platt, D. Smith, E. Vallender, R. Wiseman, X. Liu, J. Below, D. Muzny, R. Gibbs, F. Yu, J. Rogers O59 Assessing RNA structure disruption induced by single-nucleotide variation J. Lin, Y. Zhang, Z. Ouyang P1 A meta-analysis of genome-wide association studies of mitochondrial dna copy number A. Moore, Z. Wang, J. Hofmann, M. Purdue, R. Stolzenberg-Solomon, S. Weinstein, D. Albanes, C.-S. Liu, W.-L. Cheng, T.-T. Lin, Q. Lan, N. Rothman, S. Berndt P2 Missense polymorphic genetic combinations underlying down syndrome susceptibility E. S. Chen P4 The evaluation of alteration of ELAM-1 expression in the endometriosis patients H. Bahrami, A. Khoshzaban, S. Heidari Keshal P5 Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population K. K. R. Alharbi P6 Genome-associated personalized antithrombotical therapy for patients with high risk of thrombosis and bleeding M. Zhalbinova, A. Akilzhanova, S. Rakhimova, M. Bekbosynova, S. Myrzakhmetova P7 Frequency of Xmn1 polymorphism among sickle cell carrier cases in UAE population M. Matar P8 Differentiating inflammatory bowel diseases by using genomic data: dimension of the problem and network organization N. Mili, R. Molinari, Y. Ma, S. Guerrier P9 Vulnerability of genetic variants to the risk of autism among Saudi children N. Elhawary, M. Tayeb, N. Bogari, N. Qotb P10 Chromatin profiles from ex vivo purified dopaminergic neurons establish a promising model to support studies of neurological function and dysfunction S. A. McClymont, P. W. Hook, L. A. Goff, A. McCallion P11 Utilization of a sensitized chemical mutagenesis screen to identify genetic modifiers of retinal dysplasia in homozygous Nr2e3rd7mice Y. Kong, J. R. Charette, W. L. Hicks, J. K. Naggert, L. Zhao, P. M. Nishina P12 Ion torrent next generation sequencing of recessive polycystic kidney disease in Saudi patients B. M. Edrees, M. Athar, F. A. Al-Allaf, M. M. Taher, W. Khan, A. Bouazzaoui, N. A. Harbi, R. Safar, H. Al-Edressi, A. Anazi, N. Altayeb, M. A. Ahmed, K. Alansary, Z. Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. Zhang, A. Schuh, T. Stockley, S. Kamel-Reid P36 Accessing genomic evidence for clinical variants at NCBI S. Sherry, C. Xiao, D. Slotta, K. Rodarmer, M. Feolo, M. Kimelman, G. Godynskiy, C. O’Sullivan, E. Yaschenko P37 NGS-SWIFT: a cloud-based variant analysis framework using control-accessed sequencing data from DBGAP/SRA C. Xiao, E. Yaschenko, S. Sherry P38 Computational assessment of drug induced hepatotoxicity through gene expression profiling C. Rangel-Escareño, H. Rueda-Zarate P40 Flowr: robust and efficient pipelines using a simple language-agnostic approach;ultraseq; fast modular pipeline for somatic variation calling using flowr S. Seth, S. Amin, X. Song, X. Mao, H. Sun, R. G. Verhaak, A. Futreal, J. Zhang P41 Applying “Big data” technologies to the rapid analysis of heterogenous large cohort data S. J. Whiite, T. Chiang, A. English, J. Farek, Z. Kahn, W. Salerno, N. Veeraraghavan, E. Boerwinkle, R. Gibbs P42 FANTOM5 web resource for the large-scale genome-wide transcription start site activity profiles of wide-range of mammalian cells T. Kasukawa, M. Lizio, J. Harshbarger, S. Hisashi, J. Severin, A. Imad, S. Sahin, T. C. Freeman, K. Baillie, A. Sandelin, P. Carninci, A. R. R. Forrest, H. Kawaji, The FANTOM Consortium P43 Rapid and scalable typing of structural variants for disease cohorts W. Salerno, A. English, S. N. Shekar, A. Mangubat, J. Bruestle, E. Boerwinkle, R. A. Gibbs P44 Polymorphism of glutathione S-transferases and sulphotransferases genes in an Arab population A. H. Salem, M. Ali, A. Ibrahim, M. Ibrahim P46 Genetic divergence of CYP3A5*3 pharmacogenomic marker for native and admixed Mexican populations J. C. Fernandez-Lopez, V. Bonifaz-Peña, C. Rangel-Escareño, A. Hidalgo-Miranda, A. V. Contreras P47 Whole exome sequence meta-analysis of 13 white blood cell, red blood cell, and platelet traits L. Polfus, CHARGE and NHLBI Exome Sequence Project Working Groups P48 Association of adipoq gene with type 2 diabetes and related phenotypes in african american men and women: The jackson heart study S. Davis, R. Xu, S. Gebeab, P Riestra, A Gaye, R. Khan, J. Wilson, A. Bidulescu P49 Common variants in casr gene are associated with serum calcium levels in koreans S. H. Jung, N. Vinayagamoorthy, S. H. Yim, Y. J. Chung P50 Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions Y. Zhou, S. Xu P51 A Bayesian framework for generalized linear mixed models in genome-wide association studies X. Wang, V. Philip, G. Carter P52 Targeted sequencing approach for the identification of the genetic causes of hereditary hearing impairment A. A. Abuzenadah, M. Gari, R. Turki, A. Dallol P53 Identification of enhancer sequences by ATAC-seq open chromatin profiling A. Uyar, A. Kaygun, S. Zaman, E. Marquez, J. George, D. Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. Andreesen, E. Holler P61 Compound heterozygous mutation in the LDLRgene in Saudi patients suffering severe hypercholesterolemia F. Al-Allaf, A. Alashwal, Z. Abduljaleel, M. Taher, A. Bouazzaoui, H. Abalkhail, A. Al-Allaf, R. Bamardadh, M. Athar

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2016
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3. Human genome meeting 2016

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Srivastava, A. K., Wang, Y., Huang, R., Skinner, C., Thompson, T., Pollard, L., Wood, T., Luo, F., Stevenson, R., Polimanti, R., Gelernter, J., Lin, X., Lim, I. Y., Wu, Y., Teh, A. L., Chen, L., Aris, I. M., Soh, S. E., Tint, M. T., MacIsaac, J. L., Yap, F., Kwek, K., Saw, S. M., Kobor, M. S., Meaney, M. J., Godfrey, K. M., Chong, Y. S., Holbrook, J. D., Lee, Y. S., Gluckman, P. D., Karnani, N., Kapoor, A., Lee, D., Chakravarti, A., Maercker, C., Graf, F., Boutros, M., Stamoulis, G., Santoni, F., Makrythanasis, P., Letourneau, A., Guipponi, M., Panousis, N., Garieri, M., Ribaux, P., Falconnet, E., Borel, C., Antonarakis, S. E., Kumar, S., Curran, J., Blangero, J., Chatterjee, S., Akiyama, J., Auer, D., Berrios, C., Pennacchio, L., Donti, T. R., Cappuccio, G., Miller, M., Atwal, P., Kennedy, A., Cardon, A., Bacino, C., Emrick, L., Hertecant, J., Baumer, F., Porter, B., Bainbridge, M., Bonnen, P., Graham, B., Sutton, R., Sun, Q., Elsea, S., Hu, Z., Wang, P., Zhu, Y., Zhao, J., Xiong, M., Bennett, David A., Hidalgo-Miranda, A., Romero-Cordoba, S., Rodriguez-Cuevas, S., Rebollar-Vega, R., Tagliabue, E., Iorio, M., D’Ippolito, E., Baroni, S., Kaczkowski, B., Tanaka, Y., Kawaji, H., Sandelin, A., Andersson, R., Itoh, M., Lassmann, T., Hayashizaki, Y., Carninci, P., Forrest, A. R. R., Semple, C. A., Rosenthal, E. A., Shirts, B., Amendola, L., Gallego, C., Horike-Pyne, M., Burt, A., Robertson, P., Beyers, P., Nefcy, C., Veenstra, D., Hisama, F., Bennett, R., Dorschner, M., Nickerson, D., Smith, J., Patterson, K., Crosslin, D., Nassir, R., Zubair, N., Harrison, T., Peters, U., Jarvik, G., Menghi, F., Inaki, K., Woo, X., Kumar, P., Grzeda, K., Malhotra, A., Kim, H., Ucar, D., Shreckengast, P., Karuturi, K., Keck, J., Chuang, J., Liu, E. T., Ji, B., Tyler, A., Ananda, G., Carter, G., Nikbakht, H., Montagne, M., Zeinieh, M., Harutyunyan, A., Mcconechy, M., Jabado, N., Lavigne, P., Majewski, J., Goldstein, J. B., Overman, M., Varadhachary, G., Shroff, R., Wolff, R., Javle, M., Futreal, A., Fogelman, D., Bravo, L., Fajardo, W., Gomez, H., Castaneda, C., Rolfo, C., Pinto, J. A., Akdemir, K. C., Chin, L., Patterson, S., Statz, C., Mockus, S., Nikolaev, S. N., Bonilla, X. I., Parmentier, L., King, B., Bezrukov, F., Kaya, G., Zoete, V., Seplyarskiy, V., Sharpe, H., McKee, T., Popadin, K., Basset-Seguin, N., Chaabene, R. Ben, Andrianova, M., Verdan, C., Grosdemange, K., Sumara, O., Eilers, M., Aifantis, I., Michielin, O., de Sauvage, F., Antonarakis, S., Likhitrattanapisal, S., Lincoln, S., Kurian, A., Desmond, A., Yang, S., Kobayashi, Y., Ford, J., Ellisen, L., Peters, T. L., Alvarez, K. R., Hollingsworth, E. F., Lopez-Terrada, D. H., Hastie, A., Dzakula, Z., Pang, A. W., Lam, E. T., Anantharaman, T., Saghbini, M., Cao, H., Gonzaga-Jauregui, C., Ma, L., King, A., Rosenzweig, E. Berman, Krishnan, U., Reid, J. G., Overton, J. D., Dewey, F., Chung, W. K., Small, K., DeLuca, A., Cremers, F., Lewis, R. A., Puech, V., Bakall, B., Silva-Garcia, R., Rohrschneider, K., Leys, M., Shaya, F. S., Stone, E., Sobreira, N. L., Schiettecatte, F., Ling, H., Pugh, E., Witmer, D., Hetrick, K., Zhang, P., Doheny, K., Valle, D., Hamosh, A., Jhangiani, S. N., Akdemir, Z. Coban, Bainbridge, M. N., Charng, W., Wiszniewski, W., Gambin, T., Karaca, E., Bayram, Y., Eldomery, M. K., Posey, J., Doddapaneni, H., Hu, J., Sutton, V. R., Muzny, D. M., Boerwinkle, E. A., Lupski, J. R., Gibbs, R. A., Shekar, S., Salerno, W., English, A., Mangubat, A., Bruestle, J., Thorogood, A., Knoppers, B. M., Takahashi, H., Nitta, K. R., Kozhuharova, A., Suzuki, A. M., Sharma, H., Cotella, D., Santoro, C., Zucchelli, S., Gustincich, S., Mulvihill, J. J., Baynam, G., Gahl, W., Groft, S. C., Kosaki, K., Lasko, P., Melegh, B., Taruscio, D., Ghosh, R., Plon, S., Scherer, S., Qin, X., Sanghvi, R., Walker, K., Chiang, T., Muzny, D., Wang, L., Black, J., Boerwinkle, E., Weinshilboum, R., Gibbs, R., Karpinets, T., Calderone, T., Wani, K., Yu, X., Creasy, C., Haymaker, C., Forget, M., Nanda, V., Roszik, J., Wargo, J., Haydu, L., Song, X., Lazar, A., Gershenwald, J., Davies, M., Bernatchez, C., Zhang, J., Woodman, S., Chesler, E. J., Reynolds, T., Bubier, J. A., Phillips, C., Langston, M. A., Baker, E. J., Lin, N., Amos, C., Calhoun, V., Dobretsberger, O., Egger, M., Leimgruber, F., Sadedin, S., Oshlack, A., Antonio, V. A. A., Ono, N., Ahmed, Z., Bolisetty, M., Zeeshan, S., Anguiano, E., Sarkar, A., Nandineni, M. R., Zeng, C., Shao, J., Liang, T., Pham, K., Chee-Wei, Y., Dongsheng, L., Lai-Ping, W., Lian, D., Hee, R. O. Twee, Yunus, Y., Aghakhanian, F., Mokhtar, S. S., Lok-Yung, C. V., Bhak, J., Phipps, M., Shuhua, X., Yik-Ying, T., Kumar, V., Boon-Peng, H., Campbell, I., Young, M. -A., James, P., Rain, M., Mohammad, G., Kukreti, R., Pasha, Q., Akilzhanova, A. R., Guelly, C., Abilova, Z., Rakhimova, S., Akhmetova, A., Kairov, U., Trajanoski, S., Zhumadilov, Z., Bekbossynova, M., Schumacher, C., Sandhu, S., Harkins, T., Makarov, V., Glenn, R., Momin, Z., Dilrukshi, B., Chao, H., Meng, Q., Gudenkauf, B., Kshitij, R., Jayaseelan, J., Nessner, C., Lee, S., Blankenberg, K., Lewis, L., Han, Y., Dinh, H., Jireh, S., Buhay, C., Liu, X., Wang, Q., Ding, Y., Veeraraghavan, N., Yang, Y., Beaudet, A. L., Eng, C. M., Worley, K. C. C., Liu, Y., Hughes, D. S. T., Murali, S. C., Harris, R. A., English, A. C., Hampton, O. A., Larsen, P., Beck, C., Wang, M., Kovar, C. L., Salerno, W. J., Yoder, A., Richards, S., Rogers, J., Raveenedran, M., Xue, C., Dahdouli, M., Cox, L., Fan, G., Ferguson, B., Hovarth, J., Johnson, Z., Kanthaswamy, S., Kubisch, M., Platt, M., Smith, D., Vallender, E., Wiseman, R., Below, J., Yu, F., Lin, J., Zhang, Y., Ouyang, Z., Moore, A., Wang, Z., Hofmann, J., Purdue, M., Stolzenberg-Solomon, R., Weinstein, S., Albanes, D., Liu, C. S., Cheng, W. L., Lin, T. T., Lan, Q., Rothman, N., Berndt, S., Chen, E. S., Bahrami, H., Khoshzaban, A., Keshal, S. Heidari, Alharbi, K. K. R., Zhalbinova, M., Akilzhanova, A., Bekbosynova, M., Myrzakhmetova, S., Matar, M., Mili, N., Molinari, R., Ma, Y., Guerrier, S., Elhawary, N., Tayeb, M., Bogari, N., Qotb, N., McClymont, S. A., Hook, P. W., Goff, L. A., McCallion, A., Kong, Y., Charette, J. R., Hicks, W. L., Naggert, J. K., Zhao, L., Nishina, P. M., Edrees, B. M., Athar, M., Al-Allaf, F. A., Taher, M. M., Khan, W., Bouazzaoui, A., Harbi, N. A., Safar, R., Al-Edressi, H., Anazi, A., Altayeb, N., Ahmed, M. A., Alansary, K., Abduljaleel, Z., Kratz, A., Beguin, P., Poulain, S., Kaneko, M., Takahiko, C., Matsunaga, A., Kato, S., Bertin, N., Vigot, R., Plessy, C., Launey, T., Graur, D., Friis-Nielsen, J., Izarzugaza, J. M., Brunak, S., Chakraborty, A., Basak, J., Mukhopadhyay, A., Soibam, B. S., Das, D., Biswas, N., Das, S., Sarkar, S., Maitra, A., Panda, C., Majumder, P., Morsy, H., Gaballah, A., Samir, M., Shamseya, M., Mahrous, H., Ghazal, A., Arafat, W., Hashish, M., Gruber, J. J., Jaeger, N., Snyder, M., Patel, K., Bowman, S., Davis, T., Kraushaar, D., Emerman, A., Russello, S., Henig, N., Hendrickson, C., Zhang, K., Rodriguez-Dorantes, M., Cruz-Hernandez, C. D., Garcia-Tobilla, C. D. P., Solorzano-Rosales, S., Jäger, N., Chen, J., Haile, R., Hitchins, M., Brooks, J. D., Jiménez-Morales, S., Ramírez, M., Nuñez, J., Bekker, V., Leal, Y., Jiménez, E., Medina, A., Hidalgo, A., Mejía, J., Halytskiy, V., Naggert, J., Collin, G. B., DeMauro, K., Hanusek, R., Belhassa, K., Belhassan, K., Bouguenouch, L., Samri, I., Sayel, H., moufid, FZ., El Bouchikhi, I., Trhanint, S., Hamdaoui, H., Elotmani, I., Khtiri, I., Kettani, O., Quibibo, L., Ahagoud, M., Abbassi, M., Ouldim, K., Marusin, A. V., Kornetov, A. N., Swarovskaya, M., Vagaiceva, K., Stepanov, V., De La Paz, E. M. Cutiongco, Sy, R., Nevado, J., Reganit, P., Santos, L., Magno, J. D., Punzalan, F. E., Ona, D., Llanes, E., Santos-Cortes, R. L., Tiongco, R., Aherrera, J., Abrahan, L., Pagauitan-Alan, P., Morelli, K. H., Domire, J. S., Pyne, N., Harper, S., Burgess, R., Gari, M. A., Dallol, A., Alsehli, H., Gari, A., Gari, M., Abuzenadah, A., Thomas, M., Sukhai, M., Garg, S., Misyura, M., Zhang, T., Schuh, A., Stockley, T., Kamel-Reid, S., Sherry, S., Xiao, C., Slotta, D., Rodarmer, K., Feolo, M., Kimelman, M., Godynskiy, G., O’Sullivan, C., Yaschenko, E., Rangel-Escareño, C., Rueda-Zarate, H., Tayubi, I. A., Mohammed, R., Ahmed, I., Ahmed, T., Seth, S., Amin, S., Mao, X., Sun, H., Verhaak, R. G., Whiite, S. J., Farek, J., Kahn, Z., Kasukawa, T., Lizio, M., Harshbarger, J., Hisashi, S., Severin, J., Imad, A., Sahin, S., Freeman, T. C., Baillie, K., Shekar, S. N., Salem, A. H., Ali, M., Ibrahim, A., Ibrahim, M., Barrera, H. A., Garza, L., Torres, J. A., Barajas, V., Ulloa-Aguirre, A., Kershenobich, D., Mortaji, Shahroj, Guizar, Pedro, Loera, Eliezer, Moreno, Karen, De León, Adriana, Monsiváis, Daniela, Gómez, Jackeline, Cardiel, Raquel, Fernandez-Lopez, J. C., Bonifaz-Peña, V., Contreras, A. V., Polfus, L., Wang, X., Philip, V., Abuzenadah, A. A., Turki, R., Uyar, A., Kaygun, A., Zaman, S., Marquez, E., George, J., Hendrickson, C. L., Starr, D. B., Baird, M., Kirkpatrick, B., Sheets, K., Nitsche, R., Prieto-Lafuente, L., Landrum, M., Lee, J., Rubinstein, W., Maglott, D., Thavanati, P. K. R., de Dios, A. Escoto, Hernandez, R. E. Navarro, Aldrate, M. E. Aguilar, Mejia, M. R. Ruiz, Kanala, K. R. R., Shahzad, N., Huber, E., Dan, A., Herr, W., Sprotte, G., Köstler, J., Hiergeist, A., Gessner, A., Andreesen, R., Holler, E., Al-Allaf, F., Alashwal, A., Taher, M., Abalkhail, H., Al-Allaf, A., Bamardadh, R., Filiptsova, O., Kobets, M., Kobets, Y., Burlaka, I., Timoshyna, I., Kobets, M. N., Al-allaf, F. A., Mohiuddin, M. T., Zainularifeen, A., Mohammed, A., and Owaidah, T.

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4. SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum

Author

Valentina, Serpieri, Fulvio, D'Abrusco, Jennifer C, Dempsey, Yong-Han Hank, Cheng, Filippo, Arrigoni, Janice, Baker, Roberta, Battini, Enrico Silvio, Bertini, Renato, Borgatti, Angela K, Christman, Cynthia, Curry, Stefano, D'Arrigo, Joel, Fluss, Michael, Freilinger, Simone, Gana, Gisele E, Ishak, Vincenzo, Leuzzi, Hailey, Loucks, Filippo, Manti, Nancy, Mendelsohn, Laura, Merlini, Caitlin V, Miller, Ansar, Muhammad, Sara, Nuovo, Romina, Romaniello, Wolfgang, Schmidt, Sabrina, Signorini, Sabrina, Siliquini, Krzysztof, Szczałuba, Gessica, Vasco, Meredith, Wilson, Ginevra, Zanni, Eugen, Boltshauser, Dan, Doherty, Enza Maria, Valente, X, Zhang, University of Washington Center for Mendelian Genomics (UW-CMG) group, Bamshad, M.J., Leal, S.M., Nickerson, D.A., Anderson, P., Bacus, T.J., Blue, E.E., Brower, K., Buckingham, K.J., Chong, J.X., Cornejo Sánchez, D., Davis, C.P., Davis, C.J., Frazar, C.D., Gomeztagle-Burgess, K., Gordon, W.W., Horike-Pyne, M., Hurless, J.R., Jarvik, G.P., Johanson, E., Kolar, J.T., Marvin, C.T., McGee, S., McGoldrick, D.J., Mekonnen, B., Nielsen, P.M., Patterson, K., Radhakrishnan, A., Richardson, M.A., Roote, G.T., Ryke, E.L., Schrauwen, I., Shively, K.M., Smith, J.D., Tackett, M., Wang, G., Weiss, J.M., Wheeler, M.M., Yi, Q., and Zhang, X.

Subjects
Male, Proband, Pediatrics, medicine.medical_specialty, Ataxia, Cerebellar Ataxia, Cerebellar dysplasia, cerebellar diseases, Haploinsufficiency, Abnormalities, Multiple/genetics, Cerebellar Ataxia/genetics, Cerebellum/abnormalities, Cerebellum/diagnostic imaging, Eye Abnormalities/genetics, Haploinsufficiency/genetics, Humans, Intellectual Disability/genetics, Kidney Diseases, Cystic/diagnosis, Kidney Diseases, Cystic/genetics, Phenotype, Repressor Proteins/genetics, Retina/abnormalities, and neonatal diseases and abnormalities, central nervous system diseases, congenital, early diagnosis, genetic variation, hereditary, Retina, Joubert syndrome, neonatal diseases and abnormalities, Cerebellum, Intellectual Disability, Genetics, medicine, Abnormalities, Multiple, Eye Abnormalities, Genetics (clinical), business.industry, Kidney Diseases, Cystic, medicine.disease, Penetrance, Hypotonia, Repressor Proteins, Ciliopathy, medicine.symptom, business
Abstract

BackgroundJoubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies.MethodsWe reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes.ResultsHeterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents.ConclusionHeterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

Published
2021

5. Dual diagnosis of UQCRFS1 -related mitochondrial complex III deficiency and recessive GJA8 -related cataracts.

Author

Blue EE, Huang SJ, Khan A, Golden-Grant K, Boyd B, Rosenthal EA, Gillentine MA, Fleming LR, Adams DR, Wolfe L, Allworth A, Bamshad MJ, Caruana NJ, Chanprasert S, Chen J, Dargie N, Doherty D, Friederich MW, Hisama FM, Horike-Pyne M, Lee JC, Donovan TE, Hock DH, Leppig KA, Miller DE, Mirzaa G, Ranchalis J, Raskind WH, Michel CR, Reisdorph R, Schwarze U, Sheppeard S, Strohbehn S, Stroud DA, Sybert VP, Wener MH, Stergachis AB, Lam CT, Jarvik GP, Dipple KM, Van Hove JLK, and Glass IA

Abstract

Biallelic pathogenic variants in UQCRFS1 underlie a rare form of isolated mitochondrial complex III deficiency associated with lactic acidosis and a distinctive scalp alopecia previously described in two unrelated probands. Here, we describe a participant in the Undiagnosed Diseases Network (UDN) with a dual diagnosis of two autosomal recessive disorders revealed by genome sequencing: UQCRFS1 -related mitochondrial complex III deficiency and GJA8 -related cataracts. Both pathogenic variants have been reported before: UQCRFS1 (NM_006003.3:c.215-1 G>C, p.Val72_Thr81del10) in a case with mitochondrial complex III deficiency and GJA8 (NM 005267.5:c.736 G>T, p.Glu246*) as a somatic change in aged cornea leading to decreased junctional coupling. A multi-modal approach combining enzyme assays and cellular proteomics analysis provided clear evidence of complex III respiratory chain dysfunction and low abundance of the Rieske iron-sulfur protein, validating the pathogenic effect of the UQCRFS1 variant. This report extends the genotypic and phenotypic spectrum for these two rare disorders and highlights the utility of deep phenotyping and genomics data to achieve diagnosis and insights into rare disease.

Published
2024
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6. Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition.

Author

Vollger MR, Korlach J, Eldred KC, Swanson E, Underwood JG, Cheng YH, Ranchalis J, Mao Y, Blue EE, Schwarze U, Munson KM, Saunders CT, Wenger AM, Allworth A, Chanprasert S, Duerden BL, Glass I, Horike-Pyne M, Kim M, Leppig KA, McLaughlin IJ, Ogawa J, Rosenthal EA, Sheppeard S, Sherman SM, Strohbehn S, Yuen AL, Reh TA, Byers PH, Bamshad MJ, Hisama FM, Jarvik GP, Sancak Y, Dipple KM, and Stergachis AB

Abstract

Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid de novo genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes ( NBEA , PDK3 , MAB21L1 , and RB1 ) previously associated with single-gene MCs. Notably, the function of each gene was disrupted via a distinct mechanism that required integration of the four 'omes' to resolve. These included nonsense-mediated decay, fusion transcript formation, enhancer adoption, transcriptional readthrough silencing, and inappropriate X chromosome inactivation of autosomal genes. Overall, this highlights the utility of synchronized long-read multi-omic profiling for mechanistically resolving complex phenotypes., Competing Interests: Conflicts J.K., J.G.U., C.T.S., A.M.W., M.K. and I.J.M. are full-time employees at PacBio, a company developing single-molecule sequencing technologies. A.B.S. is a co-inventor on a patent relating to the Fiber-seq method (US17/995,058).

Published
2023
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7. Full-length Isoform Sequencing for Resolving the Molecular Basis of Charcot-Marie-Tooth 2A.

Author

Stergachis AB, Blue EE, Gillentine MA, Wang LK, Schwarze U, Cortés AS, Ranchalis J, Allworth A, Bland AE, Chanprasert S, Chen J, Doherty D, Folta AB, Glass I, Horike-Pyne M, Huang AY, Khan AT, Leppig KA, Miller DE, Mirzaa G, Parhin A, Raskind WH, Rosenthal EA, Sheppeard S, Strohbehn S, Sybert VP, Tran TT, Wener MH, Byers PHH, Nelson SF, Bamshad MJ, Dipple KM, Jarvik GP, Hoppins S, and Hisama FM

Abstract

Objectives: Transcript sequencing of patient-derived samples has been shown to improve the diagnostic yield for solving cases of suspected Mendelian conditions, yet the added benefit of full-length long-read transcript sequencing is largely unexplored., Methods: We applied short-read and full-length transcript sequencing and mitochondrial functional studies to a patient-derived fibroblast cell line from an individual with neuropathy that previously lacked a molecular diagnosis., Results: We identified an intronic homozygous MFN2 c.600-31T>G variant that disrupts the branch point critical for intron 6 splicing. Full-length long-read isoform complementary DNA (cDNA) sequencing after treatment with a nonsense-mediated mRNA decay (NMD) inhibitor revealed that this variant creates 5 distinct altered splicing transcripts. All 5 altered splicing transcripts have disrupted open reading frames and are subject to NMD. Furthermore, a patient-derived fibroblast line demonstrated abnormal lipid droplet formation, consistent with MFN2 dysfunction. Although correctly spliced full-length MFN2 transcripts are still produced, this branch point variant results in deficient MFN2 levels and autosomal recessive Charcot-Marie-Tooth disease, axonal, type 2A (CMT2A)., Discussion: This case highlights the utility of full-length isoform sequencing for characterizing the molecular mechanism of undiagnosed rare diseases and expands our understanding of the genetic basis for CMT2A., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Published
2023
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8. Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

Author

Pujol-Giménez J, Mirzaa G, Blue EE, Albano G, Miller DE, Allworth A, Bennett JT, Byers PH, Chanprasert S, Chen J, Doherty D, Folta AB, Gillentine MA, Glass I, Hing A, Horike-Pyne M, Leppig KA, Parhin A, Ranchalis J, Raskind WH, Rosenthal EA, Schwarze U, Sheppeard S, Strohbehn S, Sybert VP, Timms A, Wener M, Bamshad MJ, Hisama FM, Jarvik GP, Dipple KM, Hediger MA, and Stergachis AB

Subjects
Humans, Child, Heterozygote, Serine metabolism, Amino Acid Transport System ASC genetics, Amino Acid Transport System ASC metabolism, Microcephaly, Epilepsy genetics, Epileptic Syndromes
Abstract

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Published
2023
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9. Returning integrated genomic risk and clinical recommendations: The eMERGE study.

Author

Linder JE, Allworth A, Bland HT, Caraballo PJ, Chisholm RL, Clayton EW, Crosslin DR, Dikilitas O, DiVietro A, Esplin ED, Forman S, Freimuth RR, Gordon AS, Green R, Harden MV, Holm IA, Jarvik GP, Karlson EW, Labrecque S, Lennon NJ, Limdi NA, Mittendorf KF, Murphy SN, Orlando L, Prows CA, Rasmussen LV, Rasmussen-Torvik L, Rowley R, Sawicki KT, Schmidlen T, Terek S, Veenstra D, Velez Edwards DR, Absher D, Abul-Husn NS, Alsip J, Bangash H, Beasley M, Below JE, Berner ES, Booth J, Chung WK, Cimino JJ, Connolly J, Davis P, Devine B, Fullerton SM, Guiducci C, Habrat ML, Hain H, Hakonarson H, Harr M, Haverfield E, Hernandez V, Hoell C, Horike-Pyne M, Hripcsak G, Irvin MR, Kachulis C, Karavite D, Kenny EE, Khan A, Kiryluk K, Korf B, Kottyan L, Kullo IJ, Larkin K, Liu C, Malolepsza E, Manolio TA, May T, McNally EM, Mentch F, Miller A, Mooney SD, Murali P, Mutai B, Muthu N, Namjou B, Perez EF, Puckelwartz MJ, Rakhra-Burris T, Roden DM, Rosenthal EA, Saadatagah S, Sabatello M, Schaid DJ, Schultz B, Seabolt L, Shaibi GQ, Sharp RR, Shirts B, Smith ME, Smoller JW, Sterling R, Suckiel SA, Thayer J, Tiwari HK, Trinidad SB, Walunas T, Wei WQ, Wells QS, Weng C, Wiesner GL, Wiley K, and Peterson JF

Subjects
Humans, Prospective Studies, Risk Factors, Risk Assessment, Genome, Genomics methods
Abstract

Purpose: Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk., Methods: To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report and will assess uptake of care recommendations after return of results., Results: GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022., Conclusion: Return of a novel report for communicating monogenic, polygenic, and family history-based risk factors will inform the benefits of integrated genetic risk assessment for routine health care., Competing Interests: Conflict of Interest N.S.A.-H. is an employee and equity holder of 23andMe; serves as a scientific advisory board member for Allelica, Inc; received personal fees from Genentech Inc, Allelica Inc, and 23andMe; received research funding from Akcea Therapeutics; and was previously employed by Regeneron Pharmaceuticals. T.W. has grant funding from Gilead Sciences, Inc. L.O. and T.R.-B are founders of a company developing MeTree. T.S., E.D.E., and E.H. are employees and stockholders of Invitae Corporation. E.M.M. has been a consultant for Avidity Bioscience, Amgen Inc, AstraZeneca, Cytokinetics, Invitae Corporation, Janssen Pharmaceuticals, Pfizer Inc, PepGen Inc, Tenaya Therapeutics, and Stealth BioTherapeutics Inc; she is also the founder of Ikaika Therapeutics. E.E.K. received personal fees from Illumina Inc, 23andMe, and Regeneron Pharmaceuticals and serves as a scientific advisory board member for Encompass Bioscience, Foresite Labs, and Galateo Bio. B.K. is an advisory board member and stockholder of Genome Medical. M.S. is a member of the Institutional Review Board of the All of Us Research Program. E.F.P. is a paid consultant for Allecia Inc. J.F.P. is a paid consultant for Natera Inc. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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10. Assessment of a Peer Physician Coaching Partnership Between a Designated Cancer Center Genetics Service and a Community Cancer Network Hospital.

Author

Santos LG, Buzdnitskaya T, Rolf BA, Souza W, Sienko M, Ruiz-Bonilla JA, Shah B, Jewell P, Jensen L, Horike-Pyne M, Elrod JA, Crews J, Laurino M, Weeks KA, and Dubard-Gault ME

Subjects
Male, Humans, Female, Aged, Community Networks, Prospective Studies, Precision Medicine, Genetic Services, Hospitals, Community, Mentoring, Pancreatic Neoplasms, Physicians, Ovarian Neoplasms
Abstract

Background: Patients with cancer seen in rural and underserved areas disproportionately face barriers to access genetic services. Genetic testing is critical to inform treatment decisions, for early detection of another cancer, and to identify at-risk family members who may benefit from screening and prevention., Objective: To examine medical oncologists' genetic testing ordering trends for patients with cancer., Design, Setting, and Participants: This prospective quality improvement study was performed in 2 phases over 6 months between August 1, 2020, and January 31, 2021, at a community network hospital. Phase 1 focused on observation of clinic processes. Phase 2 incorporated peer coaching from cancer genetics experts for medical oncologists at the community network hospital. The follow-up period lasted 9 months., Main Outcomes and Measures: The number of genetic tests ordered was compared between phases., Results: The study included 634 patients (mean [SD] age, 71.0 [10.8] years [range, 39-90 years]; 409 women [64.5%]; 585 White [92.3%]); 353 (55.7%) had breast cancer, 184 (29.0%) had prostate cancer, and 218 (34.4%) had a family history of cancer. Of the 634 patients with cancer, 29 of 415 (7.0%) received genetic testing in phase 1, and 25 of 219 (11.4%) received genetic testing in phase 2. Of the 29 patients who received testing in phase 1, 20 (69.0%) had germline genetic testing; 23 of 25 patients (92.0%) had germline genetic testing in phase 2. Uptake of germline genetic testing increased by 23.0% between phases, but the difference was not statistically significant (P = .06). Uptake of germline genetic testing was highest among patients with pancreatic cancer (4 of 19 [21.1%]) and ovarian cancer (6 of 35 [17.1%]); the National Comprehensive Cancer Network (NCCN) recommends offering genetic testing to all patients with pancreatic cancer and ovarian cancer., Conclusions and Relevance: This study suggests that peer coaching from cancer genetics experts was associated with an increase in ordering of genetic testing by medical oncologists. Efforts made to (1) standardize gathering of personal and family history of cancer, (2) review biomarker data suggestive of a hereditary cancer syndrome, (3) facilitate ordering tumor and/or germline genetic testing every time NCCN criteria are met, (4) encourage data sharing between institutions, and (5) advocate for universal coverage for genetic testing may help realize the benefits associated with precision oncology for patients and their families seeking care at community cancer centers.

Published
2023
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11. Insurance coverage does not predict outcomes of genetic testing: The search for meaning in payer decisions for germline cancer tests.

Author

Amendola LM, Hart MR, Bennett RL, Horike-Pyne M, Dorschner M, Shirts B, and Jarvik GP

Subjects
Adult, Female, Humans, Male, Middle Aged, Exome Sequencing, Genetic Predisposition to Disease, Genetic Testing standards, Germ-Line Mutation, Insurance Coverage, Neoplasms genetics
Abstract

In this work, we explore the results of germline cancer genetic tests in individuals whose insurance would not cover this testing. We enrolled 31 patients with a personal history of cancer whose health insurer denied coverage for a clinical germline cancer panel genetic test recommended by a medical genetics provider into a study providing exome sequencing and return of cancer-related results. Five participants (16%) had a pathogenic variant identified related to increased cancer risk. Three participants (10%) had a variant of uncertain significance (VUS) in a gene related to their cancer history. These rates are not significantly different than the 12% rate of pathogenic or likely pathogenic (P/LP) variants and VUS in 1,462 patients approved by insurance to have a similar clinical germline cancer test (p = .59 for P/LP variants; p = .87 for VUS; Shirts et al., Genet Med, 18:974, 2016). Health insurance guidelines may not meaningfully differentiate between patients with cancer who are likely to benefit from germline cancer genetic testing and those who will not. Failure to identify pathogenic variants in this research cohort would have led to suboptimal care. Strategic evaluation of current germline cancer genetic testing coverage policies is needed to appropriately deliver precision medicine., (© 2019 National Society of Genetic Counselors.)

Published
2019
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12. Clinical exome sequencing vs. usual care for hereditary colorectal cancer diagnosis: A pilot comparative effectiveness study.

Author

Niu X, Amendola LM, Hart R, Bennette CS, Heagerty P, Horike-Pyne M, Trinidad SB, Rosenthal EA, Comstock B, Nefcy C, Hisama FM, Bennett RL, Grady WM, Gallego CJ, Tarczy-Hornoch P, Fullerton SM, Burke W, Regier DA, Dorschner MO, Shirts BH, Robertson PD, Nickerson DA, Patrick DL, Jarvik GP, and Veenstra DL

Subjects
Adenomatous Polyposis Coli diagnosis, Adenomatous Polyposis Coli genetics, Aged, Communication, Comparative Effectiveness Research, Confidentiality, Cost-Benefit Analysis, Exome, Female, Humans, Male, Middle Aged, Research Design, Sequence Analysis, DNA, Socioeconomic Factors, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Genetic Predisposition to Disease genetics, Health Resources statistics & numerical data, Health Services statistics & numerical data
Abstract

Background: Clinical exome sequencing (CES) provides the advantage of assessing genetic variation across the human exome compared to a traditional stepwise diagnostic approach or multi-gene panels. Comparative effectiveness research methods offer an approach to better understand the patient-centered and economic outcomes of CES., Purpose: To evaluate CES compared to usual care (UC) in the diagnostic work-up of inherited colorectal cancer/polyposis (CRCP) in a randomized controlled trial (RCT)., Methods: The primary outcome was clinical sensitivity for the diagnosis of inherited CRCP; secondary outcomes included psychosocial outcomes, family communication, and healthcare resource utilization. Participants were surveyed 2 and 4 weeks after results return and at 3-month intervals up to 1 year., Results: Evolving outcome measures and standard of care presented critical challenges. The majority of participants in the UC arm received multi-gene panels [94.73%]. Rates of genetic findings supporting the diagnosis of hereditary CRCP were 7.5% [7/93] vs. 5.4% [5/93] in the CES and UC arms, respectively (P = 0.28). Differences in privacy concerns after receiving CRCP results were identified (0.88 in UC vs 0.38 in CES, P = 0.05); however, healthcare resource utilization, family communication and psychosocial outcomes were similar between the two arms. More participants with positive results (17.7%) intended to change their life insurance 1  month after the first return visit compared to participants returned a variant of uncertain significance (9.1%) or negative result (4.8%) (P = 0.09)., Conclusion: Our results suggest that CES provides similar clinical benefits to multi-gene panels in the diagnosis of hereditary CRCP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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13. Rare loss of function variants in candidate genes and risk of colorectal cancer.

Author

Rosenthal EA, Shirts BH, Amendola LM, Horike-Pyne M, Robertson PD, Hisama FM, Bennett RL, Dorschner MO, Nickerson DA, Stanaway IB, Nassir R, Vickers KT, Li C, Grady WM, Peters U, and Jarvik GP

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Risk Factors, BRCA2 Protein genetics, Colorectal Neoplasms genetics, Deoxyribonuclease (Pyrimidine Dimer) genetics, Fanconi Anemia Complementation Group Proteins genetics, Genetic Loci, Genetic Variation, RNA Helicases genetics
Abstract

Although ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. We found a significant enrichment of PDVs in cases vs. controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR = 1.9, p = 0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p = 0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p = 0.0001), BRCA2 (p = 0.01) and BRIP1 (p = 0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P.

Published
2018
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14. Discordance in selected designee for return of genomic findings in the event of participant death and estate executor.

Author

Goodman JL, Amendola LM, Horike-Pyne M, Trinidad SB, Fullerton SM, Burke W, and Jarvik GP

Abstract

Background: Legal and ethical questions arise regarding disseminating genetic research results to family members in the event of a research participant's death; failure to return or return to legal next of kin or estate executor may not reflect participant desires. We sought to determine participant preferences for whether and to whom they would like their data released in the case of their death prior to receiving genomic results, focusing on whether the person selected was also their estate executor., Methods: The University of Washington NEXT Medicine Study of the Clinical Sequencing Exploratory Research program previously reported participant preferences regarding designating an individual to receive genomic results in the event of death, including whether they want results shared, and if so, with what person. Participants were also asked whether this designee is executor of their will or estate., Results: To date, 61 individuals were asked about the concordance of their study designee and legal representative: 42 (69%) reported having a will or estate plan and of these, 14 (33%) chose someone other than their executor to receive their results. For the 14 who chose someone other than their estate executor to receive genetic results, 12 (86%) chose a family member, typically a biological relative, as their designee. Those with a different genomic designee than their executor were less likely to be partnered ( P  = 0.0024). For those partnered participants without an estate plan, spouses were not always chosen for return of genomic results., Conclusion: For one-third of our participants, the individual deemed most appropriate by the participant to receive their genomic results was not the executor. In the absence of an explicit designation, HIPAA may prohibit access to genomic results to persons other than the executor; hence asking for designation at the time of study enrollment (or initiation of clinical testing) is important.

Published
2017
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15. Patients' Choices for Return of Exome Sequencing Results to Relatives in the Event of Their Death.

Author

Amendola LM, Horike-Pyne M, Trinidad SB, Fullerton SM, Evans BJ, Burke W, and Jarvik GP

Subjects
Adult, Aged, Aged, 80 and over, Colorectal Neoplasms genetics, Disclosure ethics, Disclosure statistics & numerical data, Female, Humans, Male, Middle Aged, Patient Preference statistics & numerical data, Young Adult, Death, Disclosure legislation & jurisprudence, Exome genetics, Genomics, Informed Consent, Patient Preference legislation & jurisprudence, Sequence Analysis
Abstract

The informed consent process for genetic testing does not commonly address preferences regarding disclosure of results in the event of the patient's death. Adults being tested for familial colorectal cancer were asked whether they want their exome sequencing results disclosed to another person in the event of their death prior to receiving the results. Of 78 participants, 92% designated an individual and 8% declined to. Further research will help refine practices for informed consent., (© 2015 American Society of Law, Medicine & Ethics, Inc.)

Published
2015
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16. Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and Polyposis Syndromes: A Cost-Effectiveness Analysis.

Author

Gallego CJ, Shirts BH, Bennette CS, Guzauskas G, Amendola LM, Horike-Pyne M, Hisama FM, Pritchard CC, Grady WM, Burke W, Jarvik GP, and Veenstra DL

Subjects
Adenomatous Polyposis Coli diagnosis, Colorectal Neoplasms diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis economics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Cost-Benefit Analysis, Decision Support Techniques, Genetic Testing, Health Care Costs, Humans, Immunohistochemistry, Models, Economic, Mutation, Phenotype, Probability, Quality-Adjusted Life Years, Adenomatous Polyposis Coli economics, Adenomatous Polyposis Coli genetics, Colorectal Neoplasms economics, Colorectal Neoplasms genetics, High-Throughput Nucleotide Sequencing economics
Abstract

Purpose: To evaluate the cost effectiveness of next-generation sequencing (NGS) panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in patients referred to cancer genetics clinics., Patients and Methods: We developed a decision model to evaluate NGS panel testing compared with current standard of care in patients referred to a cancer genetics clinic. We obtained data on the prevalence of genetic variants from a large academic laboratory and calculated the costs and health benefits of identifying relatives with a pathogenic variant, in life-years and quality-adjusted life-years (QALYs). We classified the CRCP syndromes according to their type of inheritance and penetrance of colorectal cancer. One-way and probabilistic sensitivity analyses were conducted to assess uncertainty., Results: Evaluation with an NGS panel that included Lynch syndrome genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient, resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared with standard care and a 99% probability that this panel was cost effective at a threshold of $100,000 per QALY. When compared with this panel, the addition of genes with low colorectal cancer penetrance resulted in an incremental cost-effectiveness ratio of $77,300 per QALY., Conclusion: The use of an NGS panel that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome genes as a first-line test is likely to provide meaningful clinical benefits in a cost-effective manner at a $100,000 per QALY threshold., (© 2015 by American Society of Clinical Oncology.)

Published
2015
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17. Comparative effectiveness of next generation genomic sequencing for disease diagnosis: design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes.

Author

Gallego CJ, Bennette CS, Heagerty P, Comstock B, Horike-Pyne M, Hisama F, Amendola LM, Bennett RL, Dorschner MO, Tarczy-Hornoch P, Grady WM, Fullerton SM, Trinidad SB, Regier DA, Nickerson DA, Burke W, Patrick DL, Jarvik GP, and Veenstra DL

Subjects
Adenomatous Polyposis Coli diagnosis, Adenomatous Polyposis Coli genetics, Colorectal Neoplasms psychology, Colorectal Neoplasms, Hereditary Nonpolyposis diagnosis, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Comparative Effectiveness Research, Cost-Benefit Analysis, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing economics, High-Throughput Nucleotide Sequencing methods, Humans, Precision Medicine, Sequence Analysis, DNA economics, Sequence Analysis, DNA methods, Colorectal Neoplasms diagnosis, Colorectal Neoplasms genetics, Exome, Research Design
Abstract

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes. Approximately 220 patients will be randomized and followed for 12 months after return of genomic findings. Patients will receive findings associated with colorectal cancer in a first return of results visit, and findings not associated with colorectal cancer (incidental findings) during a second return of results visit. The primary outcome is efficacy to detect mutations associated with these syndromes; secondary outcomes include psychosocial impact, cost-effectiveness and comparative costs. The secondary outcomes will be obtained via surveys before and after each return visit. The expected challenges in conducting this randomized controlled trial include the relatively low prevalence of genetic disease, difficult interpretation of some genetic variants, and uncertainty about which incidental findings should be returned to patients. The approaches utilized in this study may help guide other investigators in clinical genomics to identify useful outcome measures and strategies to address comparative effectiveness questions about the clinical implementation of genomic sequencing in clinical care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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