Author: "Antonarakis, S." / Publication Type: Magazines - Searchworks@Jio Institute Digital Library Search Results

1. 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
Published: 2016
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2. Experience of a multidisciplinary task force with exome sequencing for Mendelian disorders

Author: Fokstuen, S., Makrythanasis, P., Hammar, E., Guipponi, M., Ranza, E., Varvagiannis, K., Santoni, F., Albarca-Aguilera, M., Poleggi, M., Couchepin, F., Brockmann, C., Mauron, A., Hurst, S., Moret, C., Gehrig, C., Vannier, A., Bevillard, J., Araud, T., Gimelli, S., Stathaki, E., Paoloni-Giacobino, A., Bottani, A., Sloan-Béna, F., Sizonenko, L., Mostafavi, M., Hamamy, H., Nouspikel, T., Blouin, J., and Antonarakis, S.
Abstract: In order to optimally integrate the use of high-throughput sequencing (HTS) as a tool in clinical diagnostics of likely monogenic disorders, we have created a multidisciplinary “Genome Clinic Task Force” at the University Hospitals of Geneva, which is composed of clinical and molecular geneticists, bioinformaticians, technicians, bioethicists, and a coordinator. We have implemented whole exome sequencing (WES) with subsequent targeted bioinformatics analysis of gene lists for specific disorders. Clinical cases of heterogeneous Mendelian disorders that could potentially benefit from HTS are presented and discussed during the sessions of the task force. Debate concerning the interpretation of identified variants and the content of the final report constitutes a major part of the task force’s work. Furthermore, issues related to bioethics, genetic counseling, quality control, and reimbursement are also addressed. This multidisciplinary task force has enabled us to create a platform for regular exchanges between all involved experts in order to deal with the multiple complex issues related to HTS in clinical practice and to continuously improve the diagnostic use of HTS. In addition, this task force was instrumental to formally approve the reimbursement of HTS for molecular diagnosis of Mendelian disorders in Switzerland.
Published: 2016
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3. A cSNP map and database for human chromosome 21.

Author: Deutsch, S, Iseli, C, Bucher, P, Antonarakis, S E, and Scott, H S
Abstract: Single nucleotide polymorphisms (SNPs) are likely to contribute to the study of complex genetic diseases. The genomic sequence of human chromosome 21q was recently completed with 225 annotated genes, thus permitting efficient identification and precise mapping of potential cSNPs by bioinformatics approaches. Here we present a human chromosome 21 (HC21) cSNP database and the first chromosome-specific cSNP map. Potential cSNPs were generated using three approaches: (1) Alignment of the complete HC21 genomic sequence to cognate ESTs and mRNAs. Candidate cSNPs were automatically extracted using a novel program for context-dependent SNP identification that efficiently discriminates between true variation, poor quality sequencing, and paralogous gene alignments. (2) Multiple alignment of all known HC21 genes to all other human database entries. (3) Gene-targeted cSNP discovery. To date we have identified 377 cSNPs averaging ~1 SNP per 1.5 kb of transcribed sequence, covering 65% of known genes in the chromosome. Validation of our bioinformatics approach was demonstrated by a confirmation rate of 78% for the predicted cSNPs, and in total 32% of the cSNPs in our database have been confirmed. The database is publicly available at http://csnp.unige.ch or http://csnp.isb-sib.ch. These SNPs provide a tool to study the contribution of HC21 loci to complex diseases such as bipolar affective disorder and allele-specific contributions to Down syndrome phenotypes.
Published: 2001
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4. Differential gene expression studies to explore the molecular pathophysiology of Down syndrome

Author: Antonarakis, S. E., Lyle, R., Chrast, R., and Scott, H. S.
Published: 2001
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5. The mouse brain transcriptome by SAGE: differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals.

Author: Chrast, R, Scott, H S, Papasavvas, M P, Rossier, C, Antonarakis, E S, Barras, C, Davisson, M T, Schmidt, C, Estivill, X, Dierssen, M, Pritchard, M, and Antonarakis, S E
Abstract: Trisomy 21, or Down syndrome (DS), is the most common genetic cause of mental retardation. Changes in the neuropathology, neurochemistry, neurophysiology, and neuropharmacology of DS patients' brains indicate that there is probably abnormal development and maintenance of central nervous system structure and function. The segmental trisomy mouse (Ts65Dn) is a model of DS that shows analogous neurobehavioral defects. We have studied the global gene expression profiles of normal and Ts65Dn male and normal female mice brains (P30) using the serial analysis of gene expression (SAGE) technique. From the combined sample we collected a total of 152,791 RNA tags and observed 45,856 unique tags in the mouse brain transcriptome. There are 14 ribosomal protein genes (nine under expressed) among the 330 statistically significant differences between normal male and Ts65Dn male brains, which possibly implies abnormal ribosomal biogenesis in the development and maintenance of DS phenotypes. This study contributes to the establishment of a mouse brain transcriptome and provides the first overall analysis of the differences in gene expression in aneuploid versus normal mammalian brain cells.
Published: 2000

6. Patterns of meiotic recombination on the long arm of human chromosome 21.

Author: Lynn, A, Kashuk, C, Petersen, M B, Bailey, J A, Cox, D R, Antonarakis, S E, and Chakravarti, A
Abstract: In this study we quantify the features of meiotic recombination on the long arm of human chromosome 21. We constructed a 67. 3-centimorgan (cM) high-resolution, comprehensive, and accurate genetic linkage map of chromosome 21q using 187 highly polymorphic markers covering almost the entire long arm; 46 loci, consisting of mutually recombining marker sets, were ordered with greater than 1000:1 odds and with average interlocus distance of 1.46 cM. These markers were used to accurately identify all exchanges in 186 female and 160 male meioses and to show (1) significant excess of recombination in female versus male meioses, (2) an overall decline in female:male recombination between the centromere and the telomere, (3) greater positive chiasma interference in male than in female meioses, and (4) lack of correlation between exchange frequency and parental age. By comparing the genetic map with the 21q sequence map, we show a general trend of increasing male, but near-constant female, recombination versus physical distance across 21q, explaining the gender-specific recombination effect. The recombination rate varies considerably between genders across 21q but is the greatest (eightfold) in the pericentromeric region, with a rate of approximately 250 kb/cM in females and approximately 2125 kb/cM in males. We used information on the locations of all exchanges to construct an empirical map function that confirms the statistical findings of positive interference. These analyses reveal that occurrence of recombination on 21q is not only gender-specific but also region-specific and that recombination suppression at the centromere is not universal. We also find evidence that male exchange location is highly correlated with gene density.
Published: 2000

7. A high-resolution physical map of human chromosome 21p using yeast artificial chromosomes.

Author: Wang, S Y, Cruts, M, Del-Favero, J, Zhang, Y, Tissir, F, Potier, M C, Patterson, D, Nizetic, D, Bosch, A, Chen, H, Bennett, L, Estivill, X, Kessling, A, Antonarakis, S E, and van Broeckhoven, C
Abstract: The short arm of human chromosome 21 (21p) contains many different types of repetitive sequences and is highly homologous to the short arms of other acrocentric chromosomes. Owing to its repetitive nature and the lack of chromosome 21p-specific molecular markers, most physical maps of chromosome 21 exclude this region. We constructed a physical map of chromosome 21p using sequence tagged site (STS) content mapping of yeast artificial chromosomes (YACs). To this end, 39 STSs located on the short arm or near the centromere of chromosome 21 were constructed, including four polymorphic simple tandem repeats (STRs) and two expressed sequence tags (ESTs). Thirty YACs were selected from the St. Louis YAC library, the chromosome 21-enriched ICRF YAC library, and the CEPH YAC and megaYAC libraries. These were assembled in a YAC contig map ranging from the centromere to the rDNA gene cluster at 21p12. The total size of the region covered by YACs is estimated between 2.9 and 5 Mb. The integrity of the YAC contig was confirmed by restriction enzyme fingerprinting and fluorescence in situ hybridization (FISH). One gap with an estimated size of 400 kb remained near the telomeric end of the contig. This YAC contig map of the short arm of human chromosome 21 constitutes a basic framework for further structural and functional studies of chromosome 21p.
Published: 1999

8. NOMENCLATURE

Author: White, J.A., McAlpine, P.J., Antonarakis, S., Cann, H., Eppig, J.T., Frazer, K., Frezal, J., Lancet, D., Nahmias, J., Pearson, P., Peters, J., Scott, A., Scott, H., Spurr, N., Talbot, C., and Povey, S.
Published: 1997
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9. Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice.

Author: Semenza, G L, Koury, S T, Nejfelt, M K, Gearhart, J D, and Antonarakis, S E
Abstract: Synthesis of erythropoietin, the primary humoral regulator of erythropoiesis, in liver and kidney is inducible by anemia or hypoxia. Analysis of human erythropoietin gene expression in transgenic mice revealed that sequences located 6-14 kilobases 5' to the gene direct expression to the kidney, whereas sequences within the immediate 3'-flanking region control hepatocyte-specific expression. Human erythropoietin transcription initiation sites were differentially utilized in liver and kidney. Inducible transgene expression was precisely targeted to peritubular interstitial cells in the renal cortex that synthesize endogenous mouse erythropoietin. These studies demonstrate that multiple erythropoietin gene regulatory elements control cell-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia.
Published: 1991
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10. The cellular basis for different fetal hemoglobin levels among sickle cell individuals with two, three, and four alpha-globin genes

Author: Dover, GJ, Chang, VT, Boyer, SH, Serjeant, GR, Antonarakis, S, and Higgs, DR
Abstract: Fetal hemoglobin (HbF) levels vary widely among individuals with sickle cell anemia (SS). Previous studies have suggested that HbF levels in SS individuals with alpha-thalassemia (two or three functional alpha- globin genes) are lower than HbF levels in SS individuals with four normal alpha-globin genes. Using immunocytochemical techniques, we studied F cell production as measured by % F reticulocytes, the amount of HbF per F cell, and the preferential survival of F cells versus non- F cells in 51 subjects with four alpha genes, 32 subjects with three alpha genes, and 18 subjects with two alpha genes. Comparison between alpha-globin gene groups was performed for the total sample as well as for a subset of 82 individuals who had replicate samples and a further subset of 39 age-matched individuals. %HbF levels were 6.8, 4.9, and 4.5 percent for the total four-, three-, and two-alpha-globin-gene groups, respectively. The percentage of F reticulocytes, percentage HbF per F cell, and the enrichment ratio (% F cell/% F reticulocytes) did not change significantly with alpha-globin gene number. Moreover, no correlation existed between alpha-globin gene number and the absolute number of F cells in any group studied. However, there was a strong inverse correlation (r = -0.407, P = .0001) between non-F cell levels (1.7 +/- 2, 2.2 +/- 5, 3.0 +/- 1.0 X 10(12)/L) and decreasing alpha- globin gene number. These data suggest that falling HbF levels among SS individuals with lessened numbers of alpha-globin genes reflect prolonged survival of non-F cells and are not due to intrinsic differences in F cell production or in the amount of HbF per F cell. The improved survival of non-F cells in SS alpha-thalassemia is presumed to be due to the lower MCHC observed in such individuals.
Published: 1987
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11. Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome

Author: Zhu, D., Alcorn, D. M., Antonarakis, S. E., Levin, L. S., Huang, P. C., Mitchell, T. N., Warren, A. C., and Maumenee, I. H.
Abstract: There are three types of X-linked cataracts recorded in Mendelian Inheritance in Man (McKusick 1988): congenital total, with posterior sutural opacities in heterozygotes: congenital, with microcornea or slight microphthalmia; and the cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker close to the gene responsible for the NH syndrome, linkage analysis on 36 members in a three-generation pedigree including seven affected males and nine carrier females was performed using 31 DNA markers. A LOD score of 1.662 at 0=0.16 was obtained with probe 782 from locus DXS85 on Xp22.2–p22.3. Negative LOD scores were found at six loci on the short arm, one distal to DXS85, five proximal, and six probes spanning the long arm were highly negative. These results make the assignment of the locus for NH to the distal end of the short arm of the X chromosome likely.
Published: 1990
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12. beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site.

Author: Antonarakis, S E, Irkin, S H, Cheng, T C, Scott, A F, Sexton, J P, Trusko, S P, Charache, S, and Kazazian, H H
Abstract: beta-Thalassemia genes, although often mild in their effects, are common among American Blacks. We have begun a systematic molecular analysis of beta-thalassemia mutations in this group. DNA polymorphisms in the beta-globin gene cluster were examined among 22 beta-thalassemia chromosomes. Six different haplotypes were observed. beta-globin genes of two of these were cloned, and their phenotypes were examined both in heterologous cells upon transient expression and in vivo. The gene found in the most common haplotype (9 of 22 chromosomes) contained a single base substitution (A----G) at position -29 within the highly conserved proximal promoter element (the "TATA" box). This mutant gene directed beta-globin RNA at 25% of normal levels both in heterologous cells and in vivo. It was associated with a mild beta +-thalassemia phenotype. A different gene, isolated from an apparently rare haplotype (1 of 22 chromosomes), had a single base substitution (A----G) within the acceptor splice site of the second intervening sequence. This mutation abolished normal RNA splicing so that the only RNA made from the gene in vitro was an alternatively spliced RNA, which could not encode beta-globin. The mild deficit in beta-globin production attributable to the -29 A----G mutant allele most likely accounts for the frequently mild nature of beta-thalassemia among American Blacks.
Published: 1984
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13. Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.

Author: Higuchi, M, Antonarakis, S E, Kasch, L, Oldenburg, J, Economou-Petersen, E, Olek, K, Arai, M, Inaba, H, and Kazazian, H H
Abstract: To date it has been difficult to characterize completely a genetic disorder, such as hemophilia A, in which the involved gene is large and unrelated affected individuals have different mutations, most of which are point mutations. Toward this end, we analyzed the DNA of 29 patients with mild-to-moderate hemophilia A in which the causative mutation is likely to be a missense mutation. Using computer analysis, we determined the melting properties of factor VIII gene sequences to design primer sets for PCR amplification and subsequent denaturing gradient gel electrophoresis (DGGE). A total of 45 primer sets was chosen to amplify 99% of the coding region of the gene and 41 of 50 splice junctions. To facilitate detection of point mutations, we mixed DNA from two male patients, and both homoduplexes and heteroduplexes were analyzed. With these 45 primer sets, 26 DNAs containing previously identified point mutations in the factor VIII gene were studied, and all 26 mutations were easily distinguishable from normal. After analyzing the 29 patients with unknown mutations, we identified the disease-producing mutation in 25 (86%). Two polymorphisms and two rare normal variants were also found. Therefore, DGGE after computer analysis is a powerful method for nearly complete characterization of disease-producing mutations and polymorphisms in large genes such as that for factor VIII.
Published: 1991
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14. Origin of the beta S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both.

Author: Antonarakis, S E, Boehm, C D, Serjeant, G R, Theisen, C E, Dover, G J, and Kazazian, H H
Abstract: In order to investigate the origin(s) of the mutation(s) leading to the beta S-globin gene in North American populations of African ancestry, we analyzed DNA polymorphisms in the beta-globin gene cluster in a large number of both beta A- and beta S-globin gene-bearing chromosomes in U.S. and Jamaican Blacks. We found 16 different haplotypes of polymorphic sites associated with 170 beta S-globin gene-bearing chromosomes. The three most common beta S haplotypes, which account for 151/170 of the beta S-globin gene-bearing chromosomes, are only rarely seen in the chromosomes bearing the beta A-globin gene in these populations (6/47). Two observations suggest multiple origins or interallelic gene conversion, or both, of the beta S mutation. First, the mutation is present in all three beta-globin gene frameworks. Second, the beta S haplotypes can be divided into four groups, each of which cannot be derived from any other by less than two crossing-over events. In summary, our observation of the beta S mutation on 16 different haplotypes in African populations can be best explained by (i) a number of simple recombination events 5' to the beta-globin gene and (ii) up to four independent mutations and/or interallelic gene conversions.
Published: 1984
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15. Structure of the human CRFB4 gene: Comparison with its IFNAR neighbor

Author: Lutfalla, G., McInnis, M. G., Antonarakis, S. E., and Uzé, G.
Abstract: The cytokine receptor family consists of a growing number of structurally and evolutionarily related transmembrane receptors. CRFB4 and IFNAR are two of the most similar members of this family. They are encoded by two neighboring genes on both human chromosome 21 and murine chromosome 16. The sequence of the human CRFB4 gene was determined from the first exon to the last intron. The nature of the repetitive sequences present in the introns was analyzed and compared with those present in the human IFNAR gene. This analysis leads to considerations of the antiquity of the duplication that gave rise to both genes from a common ancestor. A pseudogene for USF has been identified in the IFNAR gene and a new definition for the repetitive sequence MER37 is proposed. The polymorphism associated with two CA repeats present in the CRFB4 gene is described.
Published: 1995
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16. β-Thalassemia in China: a Systematic Molecular Characterization of β-Thalassemia Mutations

Author: Huang, S., Waber, P. G., Dowling, C. E., Wong, C., Antonarakis, S. E., Cai, R. L., Wang, M. Q., Lo, W. H. Y., and Kazazian, H. H.
Abstract: In order to initiate a program of prenatal diagnosis for the prevention of β-thalassemia in China, we have begun systematic studies of the β-thal assemia mutations among the Chinese. DNA polymorphisms in the β-globin gene cluster were examined in 46 β-thalassemia chromosomes. Six different haplotypes were observed. One β-thalassemia gene associated with a new haplotype was cloned and sequenced. The mutation was a single base substitution (A→G) at position -29 within the highly conserved proximal promoter element (the "TATA" box). This mutation was not observed previously in the Chinese. The β-thalassemia genes were further screened with oligonucleotide probes specific for all known mutations in the Chinese. Five mutations were identified and accounted for 35 β-thalassemia alleles.
Published: 1988
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17. Isolation of the human BACH1 transcription regulator gene, which maps to chromosome 21q22.1

Author: Blouin, Jean-Louis, Duriaux Saïl, Geneviève, Guipponi, Michel, Rossier, Colette, Pappasavas, Marie-Pierre, and Antonarakis, S. E.
Abstract: Abstract: In order to contribute to the development of the transcriptional map of chromosome 21, we performed exon trapping using cosmid clones mapped in the region 21q22.1–22.2 and identified a number of potential exons. One of the trapped exons (Genbank No. AF026200) showed a strong homology with the mouse Bach1 gene (Genbank No. D86603), a transcription factor regulating gene expression. We then isolated the full-length coding region of the human BACH1 gene using expressed sequence tags, reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. The predicted BACH1 protein contains 736 amino acids and is 88% identical to its mouse homolog. It contains basic leucine zipper and BTB-zinc finger domains (which are directly involved in DNA binding for transcription regulation). The BACH1 gene maps in a relatively gene-poor region on 21q22.1 in yeast artificial chromosome 814c1 of the collection of Chumakov et al. Northern blot analysis revealed that it is expressed as an mRNA species of approximately 5.8 kb in all 16 adult and 4 fetal tissues examined; an additional mRNA species of 2.8 kb was observed in adult testis. The contribution of the BACH1 gene to the pathophysiology of trisomy or monosomy 21 is unknown. In addition, no monogenic disorders associated with mutations in the BACH1 gene have yet been identified.
Published: 1998
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18. Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region.

Author: Chrast, R, Scott, H S, Chen, H, Kudoh, J, Rossier, C, Minoshima, S, Wang, Y, Shimizu, N, and Antonarakis, S E
Abstract: As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3-q21 and 21q22.2, respectively; SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, and Drosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3' ends. Northern blot analysis revealed one mRNA SIM1 species of approximately 9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis.
Published: 1997

19. Characterization of five partial deletions of the factor VIII gene.

Author: Youssoufian, H, Antonarakis, S E, Aronis, S, Tsiftis, G, Phillips, D G, and Kazazian, H H
Abstract: Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.
Published: 1987
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20. Molecular mechanism in the formation of a human ring chromosome 21.

Author: Wong, C, Kazazian, H H, Stetten, G, Earnshaw, W C, Van Keuren, M L, and Antonarakis, S E
Abstract: We have characterized the structural rearrangements of a chromosome 21 that led to the de novo formation of a human ring chromosome 21 [r(21)]. Molecular cloning and chromosomal localization of the DNA regions flanking the ring junction provide evidence for a long arm to long arm fusion in formation of the r(21). In addition, the centromere and proximal long arm region of a maternal chromosome 21 are duplicated in the r(21). Therefore, the mechanism in formation of the r(21) was complex involving two sequential chromosomal rearrangements. (i) Duplication of the centromere and long arm of one maternal chromosome 21 occurred forming a rearranged intermediate. (ii) Chromosomal breaks in both the proximal and telomeric long arm regions on opposite arms of this rearranged chromosome occurred with subsequent reunion producing the r(21).
Published: 1989
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21. Identification of Sequence Variants and Analysis of the Role of the Catechol-O-Methyl-Transferase Gene in Schizophrenia Susceptibility

Author: Karayiorgou, M., Gogos, J. A., Galke, B. L., Wolyniec, P. S., Nestadt, G., Antonarakis, S. E., Kazazian, H. H., Housman, D. E., and Pulver, A. E.
Published: 1998
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22. Analysis of DNA haplotypes suggests a genetic predisposition to trisomy 21 associated with DNA sequences on chromosome 21.

Author: Antonarakis, S E, Kittur, S D, Metaxotou, C, Watkins, P C, and Patel, A S
Abstract: To test the hypothesis that there is a genetic predisposition to nondisjunction and trisomy 21 associated with DNA sequences on chromosome 21, we used DNA polymorphism haplotypes for chromosomes 21 to examine the distribution of different chromosomes 21 in Down syndrome and control families from the same ethnic group. The chromosomes 21 from 20 Greek families with a Down syndrome child and 27 control Greek families have been examined for DNA polymorphism haplotypes by using four common polymorphic sites adjacent to two closely linked single-copy DNA sequences (namely pW228C and pW236B), which map somewhere near the proximal long arm of chromosome 21. Three haplotypes, +, +---, and - with respective frequencies of 43/108, 24/108, and 23/108, account for the majority of chromosomes 21 in the control families. However, haplotype - was found to be much more commonly associated with chromosomes 21 that underwent nondisjunction in the Down syndrome families (frequency of 21/50; X2 for the two distributions is 9.550; P = 0.023; degrees of freedom, 3). The two populations (control and trisomic families) did not differ in the distribution of haplotypes for two DNA polymorphisms on chromosome 17. The data from this initial study suggest that the chromosome 21, which is marked in Greeks with haplotype - for the four above described polymorphic sites, is found more commonly in chromosomes that participate in nondisjunction than in controls. We propose an increased tendency for nondisjunction due to DNA sequences associated with a subset of chromosomes 21 bearing this haplotype.
Published: 1985
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23. beta-Thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects.

Author: Cheng, T C, Orkin, S H, Antonarakis, S E, Potter, M J, Sexton, J P, Markham, A F, Giardina, P J, Li, A, and Kazazian, H H
Abstract: To perform a systematic analysis of beta-thalassemia genes among Chinese, we have determined the DNA haplotype in the beta-globin gene region of 37 Chinese beta-thalassemia chromosomes. Only four haplotypes were found. Blot hybridization analysis of erythroid RNA from patients homozygous for haplotypes 1, 2, and 3 demonstrated different patterns, suggesting that a different mutation was associated with each haplotype. The mutation associated with haplotype 1 was a C----T substitution at IVS-2, position 654. This mutation produces a new donor splice site and leads to formation of a beta-globin RNA with an insertion of 73 nucleotides. The mutation associated with haplotype 2 was a nucleotide insertion of A between codons 71 and 72, which results in a frameshift and premature termination of beta-globin synthesis. Haplotype analysis suggests that these two mutations may account for up to 85% of beta-thalassemia genes in this ethnic group. The haplotype 3 gene contained a transcriptional "TATA" box mutation that has been previously reported. Oligonucleotide hybridization demonstrated that the mutation associated with haplotype 4 was the same IVS-1 position 5 substitution commonly observed among beta-thalassemia genes in Asian Indians. Since haplotype 4 of Chinese differs at polymorphic sites on either side of the IVS-1 position 5 mutation from the haplotype associated with this mutation in Indians, the mutation presumably arose independently in these two populations.
Published: 1984
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24. The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome.

Author: Economou, E P, Bergen, A W, Warren, A C, and Antonarakis, S E
Abstract: To identify DNA polymorphisms that are abundant in the human genome and are detectable by polymerase chain reaction amplification of genomic DNA, we tested the hypothesis that the polydeoxyadenylate tract of the Alu family of repetitive elements is polymorphic among human chromosomes. We analyzed the 3' ends of three specific Alu sequences and found that two (in the adenosine deaminase gene and the beta-globin pseudogene) were polymorphic. This novel class of polymorphisms, termed AluVpA [Alu variable poly(A)] may represent one of the most useful and informative group of DNA markers in the human genome.
Published: 1990
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25. Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene.

Author: Higuchi, M, Kazazian, H H, Kasch, L, Warren, T C, McGinniss, M J, Phillips, J A, Kasper, C, Janco, R, and Antonarakis, S E
Abstract: Hemophilia A is an X chromosome-linked disorder resulting from deficiency of factor VIII, an important protein in blood coagulation. A large number of disease-producing mutations have been reported in the factor VIII gene. However, a comprehensive analysis of the mutations has been difficult because of the large gene size, its many scattered exons, and the high frequency of de novo mutations. Recently, we have shown that nearly all mutations resulting in mild-to-moderate hemophilia A can be detected by PCR and denaturing gradient gel electrophoresis (DGGE). In this study, we attempted to discover the mutations causing severe hemophilia A by analyzing 47 unselected patients, 30 of whom had severe hemophilia and 17 of whom had mild-to-moderate disease. Using DGGE as a screening method, we analyzed 99% of the coding region, 94% of the splice junctions, the promoter region, and the polyadenylylation site of the gene. We found the mutation in 16 of 17 (94%) patients with mild-to-moderate disease but in only 16 of 30 (53%) patients with severe hemophilia A. Since DGGE after computer analysis appears to detect all mutations in a given fragment, the lower-than-expected yield of mutations in patients with severe disease is likely not due to failure of the detection method; it is probably due to the presence of mutations in DNA sequences outside the regions studied. Such sequences may include locus-controlling regions, other sequences within introns or outside the gene that are important for its expression, or another gene involved in factor VIII expression that is very closely linked to the factor VIII gene.
Published: 1991
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26. Beta-globin locus is linked to the parathyroid hormone (PTH) locus and lies between the insulin and PTH loci in man.

Author: Antonarakis, S E, Phillips, J A, Mallonee, R L, Kazazian, H H, Fearon, E R, Waber, P G, Kronenberg, H M, Ullrich, A, and Meyers, D A
Abstract: Using a parathyroid hormone (PTH) cDNA probe we found a common Pst I polymorphic restriction site 3' to the PTH gene in all ethnic groups examined. Because the PTH, insulin, and beta-globin loci have been localized to the short arm of chromosome 11 (11p) we used DNA polymorphisms adjacent to each of these three loci to determine whether they are genetically linked and to determine their order. We found that the PTH and beta-globin loci are closely linked (estimated recombination fraction, 0.07; 95% confidence limits, 0.05-0.10; lod score, 4.63; odds favoring linkage, 42,000:1). Furthermore, our findings strongly indicate that the beta-globin gene cluster lies between the PTH and insulin loci. Therefore, the gene order on 11p is centromere-PTH-beta-globin-insulin.
Published: 1983
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27. Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: a GABA receptor subunit highly expressed in the retina.

Author: Cutting, G R, Lu, L, O'Hara, B F, Kasch, L M, Montrose-Rafizadeh, C, Donovan, D M, Shimada, S, Antonarakis, S E, Guggino, W B, and Uhl, G R
Abstract: Type A gamma-aminobutyric acid (GABAA) receptors are a family of ligand-gated chloride channels that are the major inhibitory neurotransmitter receptors in the nervous system. Molecular cloning has revealed diversity in the subunits that compose this heterooligomeric receptor, but each previously elucidated subunit displays amino acid similarity in conserved structural elements. We have used these highly conserved regions to identify additional members of this family by using the polymerase chain reaction (PCR). One PCR product was used to isolate a full-length cDNA from a human retina cDNA library. The mature protein predicted from this cDNA sequence in 458 amino acids long and displays between 30 and 38% amino acid similarity to the previously identified GABAA subunits. This gene is expressed primarily in the retina but transcripts are also detected in the brain, lung, and thymus. Injection of Xenopus oocytes with RNA transcribed in vitro produces a GABA-responsive chloride conductance and expression of the cDNA in COS cells yields GABA-displaceable muscimol binding. These features are consistent with our identification of a GABA subunit, GABA rho 1, with prominent retinal expression that increases the diversity and tissue specificity of this ligand-gated ion-channel receptor family.
Published: 1991
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28. Report of the Fifth International Workshop on Human Chromosome 21 Mapping 1994

Author: Shimizu, N., Ohki, M., Sakaki, Y., Minoshima, S., Eki, T., Murakami, Y., Sugawara, H., Suwa, S., Antonarakis, S., Patterson, D., Van Broeckhoven, C., and Delabar, J.M.
Published: 1995
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29. Human erythropoietin gene expression in transgenic mice: multiple transcription initiation sites and cis-acting regulatory elements

Author: Semenza, G L, Dureza, R C, Traystman, M D, Gearhart, J D, and Antonarakis, S E
Abstract: Erythropoietin (EPO) is the primary humoral regulator of mammalian erythropoiesis. The single-copy EPO gene is normally expressed in liver and kidney, and increased transcription is induced by anemia or cobalt chloride administration. To identify cis-acting DNA sequences responsible for regulated expression, transgenic mice were generated by microinjection of a 4-kilobase-pair (kb) (tgEPO4) or 10-kb (tgEPO10) cloned DNA fragment containing the human EPO gene, 0.7 kb of 3'-flanking sequence, and either 0.4 or 6 kb of 5'-flanking sequence, respectively. tgEPO4 mice expressed the transgene in liver, where expression was inducible by anemia or cobalt chloride, kidney, where expression was not inducible, and other tissues that do not normally express EPO. Human EPO RNA in tgEPO10 mice was detected only in liver of anemic or cobalt-treated mice. Both tgEPO4 and tgEPO10 mice were polycythemic, demonstrating that the human EPO RNA transcribed in liver is functional. These results suggest that (i) a liver inducibility element maps within 4 kb encompassing the gene, 0.4 kb of 5'-flanking sequence, and 0.7 kb of 3'-flanking sequence; (ii) a negative regulatory element is located between 0.4 and 6 kb 5' to the gene; and (iii) sequences required for inducible kidney expression are located greater than 6 kb 5' or 0.7 kb 3' to the gene. RNase protection analysis revealed that human EPO RNA in anemic transgenic mouse liver and hypoxic human hepatoma cells is initiated from several sites, only a subset of which is utilized in nonanemic transgenic liver and human fetal liver.
Published: 1990
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30. Familial isolated aniridia associated with a translocation involving chromosomes 11 and 22 [t(11;22)(p13;q12.2)]

Author: Moore, Jay, Hyman, Susan, Antonarakis, S., Mules, Emilie, and Thomas, G.
Abstract: Isolated aniridia segregated as an autosomal dominant trait in a family with 11 affected members spanning five generations. Four of the eight individuals studied had aniridia associated with glaucoma and cataracts. Cytogenetic studies revealed an apparently balanced reciprocal translocation between chromosomes 11 and 22 [t(11;22)(p13;q12.2)], while four unaffected relatives had normal karyotypes. There is no evidence of Wilms tumor or genitourinary abnormalities in any members of the family. Restriction enzyme analysis of the human catalase gene revealed no abnormalities in the individuals with the translocation. A summary of phenotypic abnormalities in 61 cases associated with aniridia is presented, as well as a comparison of breakpoints in 44 cases of 11p deletion. These data indicate that single breaks at 11p13 are associated with isolated aniridia, while deletion of 11p13 results in aniridia combined with Wilms tumor, genitourinary abnormalities, and/or mental retardation.
Published: 1986
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31. The human gene encoding insulin-like growth factor I is located on chromosome 12

Author: Höppener, J. W. M., Pagter-Holthuizen, P., Kessel, A. H. M. Geurts, Jansen, M., Kittur, S. D., Antonarakis, S. E., Lips, C. J. M., and Sussenbach, J. S.
Abstract: A cDNA probe corresponding to mRNA encoding human somatomedin-C/insulin-like growth factor I (IGF-I) was used for the chromosomal assignment of the IGF-I gene. Southern-blot hybridization analysis of DNA from human-Chinese hamster somatic cell hybrids showed that the IGF-I gene is located on chromosome 12. Comparison of the chromosomal assignments of the IGF-I gene and two other members of the insulin gene family, with three c-ras oncogenes, reveals a remarkable association of the two gene families.
Published: 1985
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32. A method for the extraction of genomic DNA from human brain tissue fixed and stored in formalin for many years

Author: Savioz, A., Blouin, J.-L., Guidi, S., Antonarakis, S. E., and Bouras, C.
Abstract: Abstract: We report a method providing access to high molecular weight, polymerase chain reaction (PCR)-amplifiable genomic DNA from brains stored in formalin for many years. It consists mainly of an intensive proteinase K treatment of ground tissue previously embedded in agarose plugs, followed by a washing and an elution step. The method was tested on brains fixed and stored in formalin for up to 46 years. All extracted DNA show an identical pattern of degradation ranging from well-preserved (more than 20 kb) to 400-bp-long fragments. This was demonstrated for DNA extracted from the cerebellums of elderly psychiatric and geriatric patients (of more than 60 years of age), male and female, demented or not, with postmortem delays longer than 1 h and shorter than 1 day. In all these cases PCR amplification of a 838-bp-long β-actin product was successfully performed when proteinase K treatment was sufficiently effective to generate pure DNA. Thus, high molecular weight, PCR-amplifiable genomic DNA can be extracted from brains stored in formalin for almost half a century.
Published: 1997
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33. Construction of human chromosome 21-specific yeast artificial chromosomes.

Author: McCormick, M K, Shero, J H, Cheung, M C, Kan, Y W, Hieter, P A, and Antonarakis, S E
Abstract: Chromosome 21-specific yeast artificial chromosomes (YACs) have been constructed by a method that performs all steps in agarose, allowing size selection by pulsed-field gel electrophoresis and the use of nanogram to microgram quantities of DNA. The DNA sources used were hybrid cell line WAV-17, containing chromosome 21 as the only human chromosome and flow-sorted chromosome 21. The transformation efficiency of ligation products was similar to that obtained in aqueous transformations and yielded YACs with sizes ranging from 100 kilobases (kb) to greater than 1 megabase when polyamines were included in the transformation procedure. Twenty-five YACs containing human DNA have been obtained from a mouse-human hybrid, ranging in size from 200 to greater than 1000 kb, with an average size of 410 kb. Ten of these YACs were localized to subregions of chromosome 21 by hybridization of RNA probes (corresponding to the YAC ends recovered in Escherichia coli) to a panel of somatic cell hybrid DNA. Twenty-one human YACs, ranging in size from 100 to 500 kb, with an average size of 150 kb, were obtained from approximately equal to 50 ng of flow-sorted chromosome 21 DNA. Three were localized to subregions of chromosome 21. YACs will aid the construction of a physical map of human chromosome 21 and the study of disorders associated with chromosome 21 such as Alzheimer disease and Down syndrome.
Published: 1989
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34. Polycythemia in transgenic mice expressing the human erythropoietin gene.

Author: Semenza, G L, Traystman, M D, Gearhart, J D, and Antonarakis, S E
Abstract: Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5' flanking sequence and 0.7 kilobase of 3' flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver, adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.
Published: 1989
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35. On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups.

Author: Wong, C, Antonarakis, S E, Goff, S C, Orkin, S H, Boehm, C D, and Kazazian, H H
Abstract: Seven beta-thalassemia genes were characterized after they were identified as candidates for previously undescribed mutations based upon the close association of DNA polymorphism haplotypes in the beta-globin gene cluster with specific ethnic mutations. The molecular defect in four of these genes was identical, a frameshift deletion of four nucleotides (-CTTT) within codons 41 and 42. This gene represents a common Southeast Asian mutation shared by a Laotian beta-thalassemia gene, [framework 1 (FR1)], a Vietnamese (FR1), and two Chinese patients (FR3 Asian and FR1). The deletion has been observed previously in Chinese (FR1) and Asian Indians (FR2) and is an example of independent origins of the same molecular defect, possible interallelic gene conversion (as it is seen on two different beta-globin gene frameworks in Chinese), and mutant gene migration in the Asian countries. A second example of mutant gene migration was identified in an Iranian patient with a nucleotide insertion (G) between codons 8 and 9, the same mutation previously found in an Asian Indian in the same chromosomal background. The last two genes examined represent further strong evidence for independent origins of mutation. A C-to-T substitution at position -88 in an Asian Indian has been identified previously in an American Black on a different beta-globin gene framework, and a G-to-A transition at nucleotide 1 of intervening sequence 2 found in an American Black has been observed previously on a different chromosome background in Mediterraneans. This study suggests that there are not many common beta-thalassemia mutations remaining to be discovered. It also suggests that certain sequences in the beta-globin gene are relatively mutation sensitive.
Published: 1986
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36. Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

Author: Semenza, G L, Nejfelt, M K, Chi, S M, and Antonarakis, S E
Abstract: Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia.
Published: 1991
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37. Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372----histidine).

Author: Arai, M, Inaba, H, Higuchi, M, Antonarakis, S E, Kazazian, H H, Fujimaki, M, and Hoyer, L W
Abstract: An immunoadsorbent method has been developed for the direct analysis of normal and variant plasma factor VIII. Using this method, the molecular defect responsible for mild hemophilia A has been identified for a patient whose plasma factor VIII activity is 0.05 unit/ml, even though the factor VIII antigen content is 3.25 units/ml. Although the variant factor VIII has an apparently normal molecular mass and chain composition, the 92-kDa heavy chain accumulates when the variant protein is incubated with thrombin and the 44-kDa heavy chain fragment cannot be detected. In contrast, thrombin cleavage of the 80-kDa light chain to the 72-kDa fragment is normal. As these data indicate a loss of factor VIII cleavage by thrombin at arginine-372, the genetic defect was determined by polymerase-chain-reaction amplification of exon 8 of the factor VIII gene and direct sequencing of the amplified product. A single-base substitution (guanine----adenine) was identified that produces an arginine to histidine substitution at amino acid residue 372. These data identify the molecular basis of an abnormal factor VIII, "factor VIII-Kumamoto," that lacks procoagulant function because of impaired thrombin activation.
Published: 1989
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38. Hemophilia A due to mutations that create new N-glycosylation sites.

Author: Aly, A M, Higuchi, M, Kasper, C K, Kazazian, H H, Antonarakis, S E, and Hoyer, L W
Abstract: In studying the molecular defects responsible for cross-reacting material-positive hemophilia A, we have identified two patients in whom the nonfunctional factor VIII-like protein has abnormal, slower-moving heavy or light chains on SDS/PAGE. Both patients have severe hemophilia A (less than 1% of normal factor VIII activity) with a normal plasma level of factor VIII antigen. The molecular defects were identified by denaturing gradient gel electrophoresis screening of PCR-amplified products of the factor VIII-coding DNA sequence followed by nucleotide sequencing of the abnormal PCR products. In patient ARC-21, a methionine-to-threonine substitution at position 1772 in the factor VIII light chain creates a potential new N-glycosylation site at asparagine-1770. In patient ARC-22, an isoleucine-to-threonine substitution at position 566 creates a potential new N-glycosylation site at asparagine-564 in the A2 domain of the factor VIII heavy chain. The mobility of these chains on SDS/PAGE was normal after N-Glycanase digestion and procoagulant activity was generated--to a maximum of 23% and 45% of control normal plasma. Abnormal N-glycosylation, blocking factor VIII procoagulant activity, represents a newly recognized mechanism for the pathogenesis of severe hemophilia A.
Published: 1992
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39. Early-onset dementias: clinical, neuropathological and genetic characteristics

Author: Giannakopoulos, P., Hof, P. R., Savioz, A., Guimon, J., Antonarakis, S. E., and Bouras, C.
Published: 1996
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40. Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4).

Author: Karathanasis, S K, Oettgen, P, Haddad, I A, and Antonarakis, S E
Abstract: The genes coding for three proteins of the plasma lipid transport system--apolipoproteins A1 (APOA1), C3 (APOC3), and A4 (APOA4)--are closely linked and tandemly organized on the long arm of human chromosome 11. In this study the human APOA4 gene has been isolated and characterized. In contrast to APOA1 and APOC3 genes, which contain three introns, the APOA4 gene contains only two. An intron interrupting the 5' noncoding region of the APOA1 and APOC3 mRNAs is absent from the corresponding position of the APOA4 mRNA. However, similar to APOA1 and APOC3 genes, the introns of the APOA4 gene separate nucleotide sequences coding for the signal peptide and the amphipathic domains in APOA4. These results suggest that the APOA1, APOC3, and APOA4 genes were derived from a common evolutionary ancestor and indicate that during evolution the APOA4 gene lost one of its ancestral introns. Two restriction endonuclease sites, an Xba I located in the second intron of the APOA4 gene and a different Xba I located 9 kilobases 3' to the APOA4 gene, are polymorphic in Mediterranean and Northern European populations. Haplotype analysis indicated that even though these polymorphic sites are located within 9 kilobases they do not display significant nonrandom association. Finally, restriction mapping analysis of DNA from a patient with combined APOA1-APOC3 deficiency and premature coronary artery disease indicated that this patient has a structurally normal APOA4 gene.
Published: 1986
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41. Linkage map of the short arm of human chromosome 11: location of the genes for catalase, calcitonin, and insulin-like growth factor II.

Author: Kittur, S D, Hoppener, J W, Antonarakis, S E, Daniels, J D, Meyers, D A, Maestri, N E, Jansen, M, Korneluk, R G, Nelkin, B D, and Kazazian, H H
Abstract: The following order of genes on the short arm of human chromosome 11 (11p) was determined previously: parathyroid hormone (PTH)-the beta-globin gene cluster (HBBC)-HRAS1/insulin. Although it is generally agreed that HRAS1 (formerly termed c-Ha-ras-1) and the insulin gene are close to each other [1-4 centimorgans (cM)], their order on chromosome 11p is still in question. We have now added three other genes, those for catalase, calcitonin, and insulin-like growth factor II (IGF-II), to this map of chromosome 11p by use of restriction site polymorphisms adjacent to these genes in classical linkage analysis. Most importantly, we find no evidence of linkage between the catalase and HBBC loci. In addition, our data indicate that the calcitonin gene is located between the catalase gene and the PTH gene. Our best estimate of the distance between the catalase and calcitonin gene is approximately 16 cM, while that between the calcitonin and PTH genes is approximately equal to 8 cM. In agreement, very loose linkage was found between the catalase and PTH loci (approximately 26 cM). Since the catalase locus has been mapped to 11p13, these data support the view that the PTH, HBBC, HRAS1, and insulin loci are located on the distal short arm of chromosome 11. The IGF-II gene is tightly linked to both the HRAS1 oncogene and the insulin gene since no recombinants were observed between the IGF-II and the HRAS1/insulin loci. Thus, based on our linkage analysis we propose that the most likely gene order for the short arm of chromosome 11 is centromere-catalase-calcitonin-PTH-HBBC-HRAS1/insulin-tel ome re and that the IGF-II gene is very close to both the HRAS1 and the insulin genes.
Published: 1985
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42. Posterpräsentation

Author: Wirthner, D., Germond, M., Grandi, P., Paul, Janecek, Brunner, A., Linder, H., Hänggi, W., Birkhäuser, M., Macas, E., Imthurn, B., Münch, M., Rosselli, M., Keller, P., Dombi, V., DeLozier-Blanchet, C., Blouin, J., Guerne, P., Antonarakis, S., Haller, U., Walt, H., Schär, G., Köchli, O., Fink, D., Bajka, M., Haller, U., Fanger, G., Keel, B., Peschers, U., Vodusek, D., Schär, G., and Schüßler, B.
Published: 1995
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43. Evidence for multiple origins of the beta E-globin gene in Southeast Asia.

Author: Antonarakis, S E, Orkin, S H, Kazazian, H H, Goff, S C, Boehm, C D, Waber, P G, Sexton, J P, Ostrer, H, Fairbanks, V F, and Chakravarti, A
Abstract: To investigate whether recurrent mutation has contributed to the high frequency of the beta E-globin gene in Southeast Asia, we used the haplotypes at three polymorphic restriction sites within and to the 3' side of the beta-globin gene to predict the framework of 23 beta E-globin genes. These haplotypes suggested that beta E-globin genes are present in two different beta-globin gene frameworks. DNA sequence determination of one gene representing each framework demonstrated that the same mutation (GAG leads to AAG at codon 26) was present in both frameworks. Moreover, the frameworks differed at three nucleotide positions known to be polymorphic in Mediterraneans. These polymorphic sites are located 70 nucleotides to the 5' side of the beta E mutation and 382 and 1032 nucleotides to the 3' side of it. The existence of the beta E mutation in these two beta-globin gene frameworks can be explained by (i) recurrent mutation giving rise to beta E-globin, (ii) a double crossing-over event, or (iii) two single crossing-over events. Mathematical analysis suggests that the first alternative, recurrent mutation of G leads to A at the first nucleotide of codon 26, is most likely.
Published: 1982
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44. Restriction site polymorphism in the phosphoglycerate kinase gene on the X chromosome

Author: Hutz, Mara H., Michelson, A. M., Antonarakis, S. E., Orkin, S. H., and Kazazian, H. H.
Abstract: Using a human phosphoglycerate kinase (PGK) cDNA probe, we have identified a common Pst I restriction site polymorphism on the human X chromosome in all ethnic groups studied. the polymorphic Pst I site was absent in 40.4% of 94 X chromosomes of unrelated subjects. Heterozygous females can only be detected by the combined use of a Pst I digest and a Xba I+Pst I digest due to the presence of autosomal and X-linked bands of the same size in simple Pst I digests. Since 48% of females are heterozygotes for the Pst I polymorphism, this site can serve as a useful genetic marker on the long arm of X chromosome in man.
Published: 1984
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45. Base substitution at position -88 in a beta-thalassemic globin gene. Further evidence for the role of distal promoter element ACACCC.

Author: Orkin, S H, Antonarakis, S E, and Kazazian, H H
Abstract: A base substitution (C----T) at position -88 relative to the cap site was identified in the beta-globin gene cloned from an individual with a mild form of beta-thalassemia. This nucleotide change lies in the sequence ACACCC proposed as a distal promoter element. Transient expression of the mutant gene in HeLa cells revealed a modest deficit in beta-globin mRNA production. RNA processing was normal. The -88 beta-thalassemia mutation lends further support for the in vivo role of the distal element in transcription.
Published: 1984
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46. Identification de nouveaux gènes impliqués dans les carcinomes basocellulaires sporadiques

Author: Parmentier, L., Bonilla, X., King, B., Bezrukov, F., Kaya, G., Zoete, V., Seplyarskiy, V., Sharpe, H., McKee, T., Letourneau, A., Ribaux, P., Papodin, K., Basset-Seguin, N., Ben Chaabene, R., Santoni, F., Guipponi, M., Andrianova, M., Garieri, M., Verdan, C., Grosdemange, K., Sumara, O., Eilers, M., Aifantis, I., Michielin, O., de Sauvage, F., Antonarakis, S., and Nikolaev, S.
Abstract: Les carcinomes basocellulaires (BCC) sont les cancers cutanés les plus fréquents chez l’homme. Leur déterminisme est lié à l’activation de la voie hedgehog, qui est actuellement la cible d’inhibiteurs spécifiques. Néanmoins, l’implication de mutations dans des gènes liés à d’autres voies physiopathologiques n’a pas été explorée de façon systématique et exhaustive. Celles-ci pourraient intervenir dans l’agressivité tumorale et/ou la différentiation en sous-types histologiques particuliers. La recherche de variants de séquences dans l’ADN tumoral, à l’aide de techniques de séquençage à haut débit des parties codantes du génome (« exome sequencing »), est une première approche pour appréhender cette question.
Published: 2016
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47. Chromosome 21: from sequence to applications

Author: Antonarakis, S
Published: 2001

48. Primary Ciliary Dyskinesia: A search for the responsible genes through linkage and candidate gene approaches

Author: Delozier-Blanchet, C D, Bartoloni, L, Gehriq, C, Radhakrishna, U, Meeks, M, Duriaux-Sail, G, Maiti, A, Guerne, P A, Walt, H, Gardiner, R M, Antonarakis, S E, and Blouin, J L
Abstract: Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder in which dysmotility to immobility of cilia and flagella result in upper respiratory tract infections, bronchiectasis and male sub-fertility. About half of patients have situs inversus (Kartagener syndrome). Extensive genetic heterogeneity is expected given the complex ultrastructure of cilia and flagella. Recently, the first report of mutations in a specific gene (DNAI1) were reported in a single Kartagener patient (Pennarun et al., AM J HUM GENET 65 suppl, A35, 1999). In Switzerland and as part of a European consortium, we collected DNA samples from 61 families, 31 of which had two or more affected members. A genome-wide linkage search was performed using 188 evenly-spaced microsatellites. Linkage analysis was performed in all families with two affecteds, and in sub-sets of families with situs inversus and with dynein arm deficiency. Data was analyzed using both parametric and non-parametric methods. Although no marker showed statistically-significant values for linkage, several chromosomal regions (4q, 5p, 8p, 16p, and 19q) were identified with suggestive scores. These findings support the hypothesis that mutations in several distinct genes may produce the PCD/ Kartagener phenotypes. As dyneins are good candidates for this disorder, we are currently screening PCD patients for mutations in dynein-related genes mapping to the pinpointed chromosomal regions. Supported by the Swiss OFES (950458) and the Milena Carvajal Foundation, Geneva.
Published: 2000
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49. 221. Schizophrenia: the identification of genetic subgroups

Author: Pulver, A. E., Antonarakis, S. E., Blouin, J. L., Housman, D., Kazazian, H. H., Lasseter, V. K., Mulle, J. G., Nestadt, G., and Wolyniec, P. S.
Published: 2000
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50. 800 ANAIXSIS OF DNA HAPLOTYPES SUGGESTS A GENETIC PREDISPOSITION TO TRISOMY 21 ASSOCIATED WITH DNA SEQUENCES ON CHROMOSOME 21

Author: Antonarakis, S E, Kittur, S D, Metaxotou, C, Patel, A S, Watkins, P E, and Kazazian, H H
Abstract: To test the hypothesis that there is a genetic predisposition to non-disjunction (NDJ) associated with DNA sequences on chromosome 21 (C21), we used DNA polymorphism haplotypes for C21s to examine the distribution of different C21s in Down Syndrome (DS) and control families. The C21s from 20 Greek families with DS and 27 control Greek families have been examined for haplotypes using four common polymorphic sites adjacent to two very closely linked single copy DNA sequences which map to the proximal long arm of C21. Three haplotypes ++++, +——, -+++ with frequencies of 43/108, 24/108, 23/108, respectively, account for the majority of C21s in the control families. However, in the DS families haplotype -+++ was commonly associated with C21s which underwent NDJ (frequency 21/50, X2= 9.6, p=0.023, df=3). There was no difference between the haplotypes of C21s which did not participate in NDJ in the DS families and those of the control families. In addition, DS and control families did not differ in the distribution of haplotypes for two DNA polymorphisms on chromosome 17. We conclude that the C21 which is marked in Greeks by -+++ for the four polymorphic sites examined is found much more commonly in chromosomes which participate in NDJ than in controls. We propose an increased tendency for NDJ due to DNA sequences associated with a subset of C21s bearing this haplotype.
Published: 1985
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