Whole-genome sequencing of a sporadic primary immunodeficiency cohort
Autor: | Thaventhiran, James E.D., Lango Allen, Hana, Burren, Oliver S., Rae, William, Greene, Daniel, Staples, Emily, Zhang, Zinan, Farmery, James H.R., Simeoni, Ilenia, Rivers, Elizabeth, Maimaris, Jesmeen, Penkett, Christopher J., Stephens, Jonathan, Deevi, Sri V.V., Sanchis-Juan, Alba, Gleadall, Nicholas S., Thomas, Moira J., Sargur, Ravishankar B., Gordins, Pavels, Baxendale, Helen E., Brown, Matthew, Tuijnenburg, Paul, Worth, Austen, Hanson, Steven, Linger, Rachel J., Buckland, Matthew S., Rayner-Matthews, Paula J., Gilmour, Kimberly C., Samarghitean, Crina, Seneviratne, Suranjith L., Sansom, David M., Lynch, Andy G., Megy, Karyn, Ellinghaus, Eva, Ellinghaus, David, Jorgensen, Silje F., Karlsen, Tom H., Stirrups, Kathleen E., Cutler, Antony J., Kumararatne, Dinakantha S., Chandra, Anita, Edgar, J. David M., Herwadkar, Archana, Cooper, Nichola, Grigoriadou, Sofia, Huissoon, Aarnoud P., Goddard, Sarah, Jolles, Stephen, Schuetz, Catharina, Boschann, Felix, Abbs, Stephen, Adhya, Zoe, Adlard, Julian, Afzal, Maryam, Ahmed, Irshad, Ahmed, Munaza, Ahmed, Saeed, Aitman, Timothy J., Alachkar, Hana, Alamelu, Jayanthi, Alikhan, Raza, Allen, Carl E., Allen, Louise, Allsup, David J., Alvi, Arif, Ambegaonkar, Gautam, Anantharachagan, Ariharan, Ancliff, Philip, Anderson, Julie, Antrobus, Richard, Armstrong, Ruth, Arno, Gavin, Arumugakani, Gururaj, Arya, Rita, Ashford, Sofie, Astle, William J., Attwood, Anthony, Austin, Steve, Aydinok, Yesim, Ayub, Waqar, Babbs, Christian, Bacchelli, Chiara, Baglin, Trevor, Bakchoul, Tamam, Bariana, Tadbir K., Barratt, Jonathan, Barwell, Julian, Baski, John, Bates, Rachel W., Batista, Joana, Baynam, Gareth, Bennett, David L., Bethune, Claire, Bhatnagar, Neha, Bibi, Shahnaz, Bierzynska, Agnieszka, Biss, Tina, Bitner-Glindzicz, Maria A.K., Bleda, Marta, Blesneac, Iulia, Boardman, Barbara, Boddana, Preetham, Bogaard, Harm J., Booth, Claire, Boyce, Sara, Bradley, John R., Brady, Angela, Breen, Gerome, Brennan, Paul, Brewer, Carole, Briley, Annette, Brown, Richard, Browning, Michael J., Brownlie, Mary, Bryson, Christine J., Buchan, Rachel J., Buck, Jackie, Bueser, Teofila, Diz, Carmen Bugarin, Burns, Siobhan O., Calleja, Paul, Carmichael, Jenny, Carr-White, Gerald, Carss, Keren J., Casey, Ruth, Chalmers, Elizabeth, Chambers, Jenny, Chambers, John, Chan, Melanie M.Y., Chan, Melissa V., Cheng, Floria, Chinn, Ivan K., Chinnery, Patrick F., Chitre, Manali, Chong, Sam, Christian, Martin T., Church, Colin, Clement, Emma M., Brod, Naomi Clements, Clifford, Hayley, Clowes, Virginia E., Coghlan, Gerry, Colby, Elizabeth, Cole, Trevor R.P., Collins, Janine H., Collins, Peter W., Condliffe, Robin, Cook, H. Terence, Cook, Stuart, Cookson, Victoria, Corris, Paul A., Creaser-Myers, Amanda, Crisp-Hihn, Abigail, Curry, Nicola S., Da Costa, Rosa, Danesino, Cesare, Daniels, Matthew J., Darby, Damaris, Daugherty, Louise C., Davies, E. G., Davies, Sophie, Davis, John, de Bree, Godelieve J., Deacock, Sarah, Deegan, Patrick B., Dempster, John, Dent, Timothy, Deshpande, Charu, Devlin, Lisa A., Dewhurst, Eleanor F., Dixit, Anand K., Dixon, Peter H., Doffinger, Rainer, Dolling, Helen, Dormand, Natalie, Downes, Kate, Drazyk, Anna M., Drewe, Elizabeth, Duarte, Daniel, Dutt, Tina, Edwards, Karen E., Egner, William, Ekani, Melanie N., El-Shanawany, Tariq, Elkhalifa, Shuayb, Elston, Tony, Emmerson, Ingrid, Erber, Wendy N., Erwood, Marie, Estiu, Maria C., Evans, Dafydd Gareth, Evans, Gillian, Everington, Tamara, Eyries, Mélanie, Favier, Remi, Firth, Helen V., Fitzpatrick, Maggie M., Fletcher, Debra, Flinter, Frances A., Fox, James C., Frary, Amy J., French, Courtney E., Freson, Kathleen, Frontini, Mattia, Furie, Bruce, Gale, Daniel P., Gall, Henning J., Gardham, Alice, Gaspar, H. Bobby, Gattens, Michael, Ghali, Neeti, Ghataorhe, Pavandeep K., Ghio, Stefano, Ghofrani, Hossein Ardeschir, Ghurye, Rohit, Gibbs, J. Simon R., Gilbert, Rodney D., Girerd, Barbara, Girling, Joanna C., Gissen, Paul, Gorman, Kathleen M., Gosal, David, Graf, Stefan, Grassi, Luigi, Greenhalgh, Alan J., Greenhalgh, Lynn, Greinacher, Andreas, Gresele, Paolo, Griffiths, Philip G., Griffiths, Sian, Grozeva, Detelina, Hackett, Scott J., Hadden, Robert D.M., Hadinnapola, Charaka, Hague, Rosie, Hague, William M., Haimel, Matthias, Hall, Matthew, Halmagyi, Csaba, Hammerton, Tracey, Hanson, Helen L., Harkness, Kirsty, Harper, Andrew R., Harper, Lorraine, Harris, Claire, Harrison, Claire, Hart, Daniel, Hassan, Ahamad, Hayman, Grant, Heemskerk, Johan W.M., Hegde, Shivaram, Henderson, Alex, Henderson, Robert H., Hensiek, Anke, Henskens, Yvonne M.C., Hodgson, Joshua, Hoffman, Jonathan, Holden, Simon, Holder, Muriel, Horvath, Rita, Houlden, Henry, Houweling, Arjan C., Howard, Luke S., Hu, Fengyuan, Hudson, Gavin, Hughes, Sean, Hughes, Stephen, Huis in ‘t Veld, Anna E., Humbert, Marc, Hurles, Matthew E., Hurst, Jane A., Irvine, Val, Izatt, Louise, James, Roger, Jeevaratnam, Praveen, Johnson, Mark, Johnson, Sally A., Jolley, Jennifer D., Jones, Bryony, Jones, Julie, Josifova, Dragana, Jurkute, Neringa, Karim, Yousuf M., Karoshi, Mahantesh A., Kasanicki, Mary A., Kazkaz, Hanadi, Kazmi, Rashid, Keeling, David, Kelleher, Peter, Kelly, Anne M., Kempster, Carly, Kennedy, Fiona, Kiani, Sorena, Kiely, David G., Kingston, Nathalie, Kinsey, Sally, Klein, Nigel, Klima, Robert, Knox, Ellen, Kostadima, Myrto A., Kovacs, Gabor, Koziell, Ania B., Kreuzhuber, Roman, Krishnakumar, Deepa, Kuijpers, Taco W., Kumar, Ajith, Kurian, Manju A., Laffan, James, Laffan, Michael A., Lalloo, Fiona, Lambert, Michele P., Lawman, Sarah H.A., Lawrie, Allan, Layton, D. Mark, Lear, Sara E., Lees, Melissa M., Lentaigne, Claire, Levine, Adam P., Lewington, Andrew J.P., Li, Wei, Liesner, Ri, Liu, Bin, Longhurst, Hilary, Lorenzo, Lorena E., Louka, Eleni, Hadeler, Silvia Lucato, Lyons, Paul A., Macdougall, Malcolm, Machado, Rajiv D., MacKenzie Ross, Robert V., Mackillop, Lucy H., MacLaren, Robert, Madan, Bella, Magee, Laura, Mahdi-Rogers, Mohamed, Maher, Eamonn R., Makris, Mike, Mangles, Sarah, Manson, Ania, Manzur, Adnan, Mapeta, Rutendo, Marchbank, Kevin J., Mark, Patrick B., Marks, Stephen, Markus, Hugh S., Marschall, Hanns Ulrich, Marshall, Andrew, Martin, Jennifer M., Masati, Larahmie, Mathias, Mary, Matser, Vera, Matthews, Emma L., Maw, Anna, Maxwell, Heather, McAlinden, Paul, McCarthy, Mark I., McDermott, Elizabeth M., McGowan, Simon J., McJannet, Coleen, McKinney, Harriet, Meacham, Stuart, Mead, Adam J., Castello, Ignacio Medina, Meehan, Sharon, Mehta, Sarju, Mercer, Catherine L., Michaelides, Michel, Michell, Anna C., Milford, David, Millar, Carolyn M., Millar, Hazel, Mistry, Anoop, Moenen, Floor, Moledina, Shahin, Montani, David, Moore, Anthony T., Moore, Jason, Morrell, Nicholas W., Morrisson, Valerie, Mozere, Monika, Muir, Keith W., Mumford, Andrew D., Murng, Sai H.K., Nasir, Iman, Nejentsev, Sergey, Newnham, Michael, Ng, Joanne, Ngoh, Adeline, Noorani, Sadia, Noori, Muna, Nurden, Paquita, O’Sullivan, Jennifer M., Obaji, Samya, Okoli, Steven, Oksenhendler, Eric, Olschewski, Andrea, Olschewski, Horst, Ong, Albert C.M., Ong, Kai Ren, Oram, Helen, Ormondroyd, Elizabeth, Othman, Shokri, Ouwehand, Willem H., Pantazis, Antonis, Papadia, Sofia, Papandreou, Apostolos, Park, Soo Mi, Parker, Alasdair P.J., Parry, David, Parsons, Georgina, Pasi, K. John, Paterson, Joan, Payne, Jeanette H., Peacock, Andrew J., Peerlinck, Kathelijne, Pepke-Zaba, Joanna, Perry, David, Petersen, Romina, Piechowski-Jozwiak, Bartlomiej, Pinto, Fernando, Polwarth, Gary J., Ponsford, Mark J., Prasad, Sanjay, Prokopenko, Inga, Psaila, Beth, Pyle, Angela, Qasim, Waseem, Quinn, Ellen, Quinti, Isabella, Raina, Sanjay, Ranganathan, Lavanya, Rankin, Julia, Rankin, Stuart, Rao, Anupama, Raymond, F. Lucy, Rehnstrom, Karola, Reid, Evan, Reilly, Mary M., Renton, Tara, Revel-Vilk, Shoshana, Rhodes, Christopher J., Rice, Andrew S.C., Richards, Emma E., Richards, Mike, Richardson, Sylvia, Richter, Alex, Robert, Leema, Roberts, Irene, Rondina, Matthew T., Rosser, Elisabeth, Rothwell, Peter, Roughley, Catherine, Roy, Noemi B., Rue-Albrecht, Kevin, Sadeghi-Alavijeh, Omid, Saleem, Moin A., Salmon, Richard M., Samani, Nilesh J., Sambrook, Jennifer G., Sandford, Richard, Santra, Saikat, Satchell, Simon C., Savic, Sinisa, Scelsi, Laura, Schotte, Gwen, Schulman, Sol, Schulze, Harald, Scott, Richard, Scully, Marie, Searle, Claire, Seeger, Werner, Sewell, W. A.Carrock, Seyres, Denis, Shackley, Fiona, Shamardina, Olga, Shapiro, Susan E., Sharma, Pankaj, Shehata, Hassan A., Shipley, Deborah, Shtoyerman, Rakefet, Sibson, Keith, Side, Lucy, Simpson, Michael, Sims, Matthew C., Sinha, Manish D., Sivapalaratnam, Suthesh, Skytte, Anne Bine, Smith, Kenneth G.C., Snape, Katie, Sneddon, Linda, Sohal, Aman, Soubrier, Florent, Southgate, Laura, Southwood, Mark, Splitt, Miranda, Staines, Simon, Stark, Hannah, Stauss, Hans, Steele, Cathal L., Stein, Daniel, Stein, Penelope E., Stock, Sophie, Stubbs, Matthew J., Suntharalingam, Jay, Swietlik, Emilia M., Symington, Emily, Tait, R. Campbell, Talks, Kate, Tan, Rhea Y.Y., Taylor, Gordon B., Thachil, Jecko, Themistocleous, Andreas C., Thomas, David C., Thomas, Ellen, Thomas, Patrick, Thompson, Dorothy A., Thomson, Kate, Thrasher, Adrian J., Thys, Chantal, Tilly, Tobias, Tischkowitz, Marc, Titterton, Catherine, Todd, John A., Toh, Cheng Hock, Tool, Anton T.J., Toshner, Mark R., Traylor, Matthew, Treacy, Carmen M., Treadaway, Paul, Trembath, Richard C., Trippier, Sarah, Tuna, Salih, Turek, Wojciech, Turro, Ernest, Upton, Paul D., Urniaz, Rafal, Vale, Tom, Van Geet, Chris, van Zuydam, Natalie, Vandersteen, Anthony M., Vazquez-Lopez, Marta, Veltman, Marijcke W.M., Vogt, Julie, von Ziegenweidt, Julie, Noordegraaf, Anton Vonk, Vora, Ajay, Vries, Minka J.A., Wakeling, Emma L., Walker, Neil, Walker, Suellen M., Walsh, Roddy, Wanjiku, Ivy, Ware, James S., Warner, Timothy Q., Wassmer, Evangeline, Watkins, Hugh, Watson, Henry G., Watt, Christopher, Waugh, Dean, Webb, Nick, Webster, Andrew R., Wei, Wei, Welch, Angela, Welch, Steven B., Werring, David, Wessels, Julie, Westbury, Sarah K., Westwood, John Paul W., Wharton, John, Whitehorn, Deborah, Whitworth, James, Wilkins, Martin R., Willcocks, Lisa, Williams, David J., Williamson, Catherine, Wong, Edwin K.S., Wood, Nicholas, Wood, Yvette, Woods, Christopher Geoffrey, Woodward, Emma R., Workman, Sarita, Wort, Stephen J., Yates, Katherine, Yeatman, Nigel, Yong, Patrick F.K., Young, Timothy, Yu, Ping, Yu-Wai-Man, Patrick, Zlamalova, Eliska |
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Přispěvatelé: | Wellcome Trust, Thaventhiran, James [0000-0001-8616-074X], Lango Allen, Hana [0000-0002-7803-8688], Burren, Oliver [0000-0002-3388-5760], Rae, William [0000-0003-0095-2514], Zhang, Zinan [0000-0003-3831-2272], Megy, Karyn [0000-0002-2826-3879], Johnson, Kathleen [0000-0002-6823-3252], Smith, Kenneth [0000-0003-3829-4326], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, Ege Üniversitesi, Experimental Immunology, Graduate School, AII - Inflammatory diseases, Infectious diseases, APH - Aging & Later Life, APH - Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, ARD - Amsterdam Reproduction and Development, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Human genetics, APH - Quality of Care, ACS - Atherosclerosis & ischemic syndromes, Biochemie, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, Faculteit FHML Centraal, MUMC+: DA CDL Algemeen (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), Interne Geneeskunde, Promovendi CD |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Protein Tyrosine Phosphatase Non-Receptor Type 2/genetics Genome-wide association study VARIANTS Regulatory Sequences Nucleic Acid medicine.disease_cause Genome Cohort Studies 0302 clinical medicine RARE QR180 Immunology Primary Immunodeficiency Consortium for the NIHR Bioresource Genetics Protein Tyrosine Phosphatase Non-Receptor Type 2 Multidisciplinary Suppressor of Cytokine Signaling 1 Protein/genetics GENETIC-VARIATION RNA-Binding Proteins Primary Immunodeficiency Diseases/diagnosis ASSOCIATION Penetrance Multidisciplinary Sciences DEFICIENCY QR180 Science & Technology - Other Topics Female General Science & Technology Primary Immunodeficiency Diseases Transcription Factors/genetics Genomics COMMON VARIABLE IMMUNODEFICIENCY QH426 Genetics Biology Article Actin-Related Protein 2-3 Complex 03 medical and health sciences Suppressor of Cytokine Signaling 1 Protein SDG 3 - Good Health and Well-being SUPPRESSOR Actin-Related Protein 2-3 Complex/genetics medicine Humans QH426 Whole genome sequencing Science & Technology Whole Genome Sequencing Common variable immunodeficiency DAS Bayes Theorem Immune dysregulation Regulatory Sequences Nucleic Acid/genetics medicine.disease RNA-Binding Proteins/genetics STAT1 MUTATIONS 030104 developmental biology Primary immunodeficiency IUIS PHENOTYPIC CLASSIFICATION GAIN 030215 immunology Genome-Wide Association Study Transcription Factors |
Zdroj: | Primary Immunodeficiency Consortium for the NIHR Bioresource, Evans, D G & Daniels, M J 2020, ' Whole-genome sequencing of a sporadic primary immunodeficiency cohort ', Nature, vol. 583, no. 7814, pp. 90-95 . https://doi.org/10.1038/s41586-020-2265-1, https://doi.org/10.1038/s41586-020-2265-1 Nature, 583(7814), 90-95. Nature Publishing Group Thaventhiran, J E D, Lango Allen, H, Burren, O S, Rae, W, Greene, D, Staples, E, Zhang, Z, Farmery, J H R, Simeoni, I, Rivers, E, Maimaris, J, Penkett, C J, Stephens, J, Deevi, S V V, Sanchis-Juan, A, Gleadall, N S, Thomas, M J, Sargur, R B, Gordins, P, Baxendale, H E, Brown, M, Tuijnenburg, P, Worth, A, Hanson, S, Linger, R J, Buckland, M S, Rayner-Matthews, P J, Gilmour, K C, Samarghitean, C, Seneviratne, S L, Sansom, D M, Lynch, A G, Megy, K, Ellinghaus, E, Ellinghaus, D, Jorgensen, S F, Karlsen, T H, Stirrups, K E, Cutler, A J, Kumararatne, D S, Chandra, A, Edgar, J D M, Herwadkar, A, Cooper, N, Grigoriadou, S, Huissoon, A P, Goddard, S, Jolles, S, Schuetz, C, Boschann, F, Abbs, S, Adhya, Z, Adlard, J, Afzal, M, Ahmed, I, Ahmed, M, Ahmed, S, Aitman, T J, Alachkar, H, Alamelu, J, Alikhan, R, Allen, C E, Allen, L, Allsup, D J, Alvi, A, Ambegaonkar, G, Anantharachagan, A, Ancliff, P, Anderson, J, Antrobus, R, Armstrong, R, Arno, G, Arumugakani, G, Arya, R, Ashford, S, Astle, W J, Attwood, A, Austin, S, Aydinok, Y, Ayub, W, Babbs, C, Bacchelli, C, Baglin, T, Bakchoul, T, Bariana, T K, Barratt, J, Barwell, J, Baski, J, Bates, R W, Batista, J, Baxendale, H E, Baynam, G, Bennett, D L, Bethune, C, Bhatnagar, N, Bibi, S, Bierzynska, A, Biss, T, Bitner-Glindzicz, M A K, Bleda, M, Blesneac, I, Boardman, B, Boddana, P, Bogaard, H J, Booth, C, Boyce, S, Bradley, J R, Brady, A, Breen, G, Brennan, P, Brewer, C, Briley, A, Brown, M, Brown, R, Browning, M J, Brownlie, M, Bryson, C J, Buchan, R J, Buck, J, Buckland, M S, Bueser, T, Diz, C B, Burns, S O, Burren, O S, Calleja, P, Carmichael, J, Carr-White, G, Carss, K J, Casey, R, Chalmers, E, Chambers, J, Chambers, J, Chan, M M Y, Chan, M V, Chandra, A, Cheng, F, Chinn, I K, Chinnery, P F, Chitre, M, Chong, S, Christian, M T, Church, C, Clement, E M, Brod, N C, Clifford, H, Clowes, V E, Coghlan, G, Colby, E, Cole, T R P, Collins, J H, Collins, P W, Condliffe, R, Cook, H T, Cook, S, Cookson, V, Cooper, N, Corris, P A, Creaser-Myers, A, Crisp-Hihn, A, Curry, N S, Cutler, A J, Da Costa, R, Danesino, C, Daniels, M J, Darby, D, Daugherty, L C, Davies, E G, Davies, S, Davis, J, de Bree, G J, Deacock, S, Deegan, P B, Deevi, S V V, Dempster, J, Dent, T, Deshpande, C, Devlin, L A, Dewhurst, E F, Dixit, A K, Dixon, P H, Doffinger, R, Dolling, H, Dormand, N, Downes, K, Drazyk, A M, Drewe, E, Duarte, D, Dutt, T, Edgar, J D M, Edwards, K E, Egner, W, Ekani, M N, El-Shanawany, T, Elkhalifa, S, Elston, T, Emmerson, I, Erber, W N, Erwood, M, Estiu, M C, Evans, D G, Evans, G, Everington, T, Eyries, M, Farmery, J H R, Favier, R, Firth, H V, Fitzpatrick, M M, Fletcher, D, Flinter, F A, Fox, J C, Frary, A J, French, C E, Freson, K, Frontini, M, Furie, B, Gale, D P, Gall, H J, Gardham, A, Gaspar, H B, Gattens, M, Ghali, N, Ghataorhe, P K, Ghio, S, Ghofrani, H A, Ghurye, R, Gibbs, J S R, Gilbert, R D, Gilmour, K C, Girerd, B, Girling, J C, Gissen, P, Gleadall, N S, Goddard, S, Gordins, P, Gorman, K M, Gosal, D, Graf, S, Grassi, L, Greene, D, Greenhalgh, A J, Greenhalgh, L, Greinacher, A, Gresele, P, Griffiths, P G, Griffiths, S, Grigoriadou, S, Grozeva, D, Hackett, S J, Hadden, R D M, Hadinnapola, C, Hague, R, Hague, W M, Haimel, M, Hall, M, Halmagyi, C, Hammerton, T, Hanson, H L, Harkness, K, Harper, A R, Harper, L, Harris, C, Harrison, C, Hart, D, Hassan, A, Hayman, G, Heemskerk, J W M, Hegde, S, Henderson, A, Henderson, R H, Hensiek, A, Henskens, Y M C, Herwadkar, A, Hodgson, J, Hoffman, J, Holden, S, Holder, M, Horvath, R, Houlden, H, Houweling, A C, Howard, L S, Hu, F, Hudson, G, Hughes, S, Hughes, S, Huis in ‘t Veld, A E, Huissoon, A P, Humbert, M, Hurles, M E, Hurst, J A, Irvine, V, Izatt, L, James, R, Jeevaratnam, P, Johnson, M, Johnson, S A, Jolles, S, Jolley, J D, Jones, B, Jones, J, Josifova, D, Jurkute, N, Karim, Y M, Karoshi, M A, Kasanicki, M A, Kazkaz, H, Kazmi, R, Keeling, D, Kelleher, P, Kelly, A M, Kempster, C, Kennedy, F, Kiani, S, Kiely, D G, Kingston, N, Kinsey, S, Klein, N, Klima, R, Knox, E, Kostadima, M A, Kovacs, G, Koziell, A B, Kreuzhuber, R, Krishnakumar, D, Kuijpers, T W, Kumar, A, Kumararatne, D S, Kurian, M A, Laffan, J, Laffan, M A, Lalloo, F, Lambert, M P, Lango Allen, H, Lawman, S H A, Lawrie, A, Layton, D M, Lear, S E, Lees, M M, Lentaigne, C, Levine, A P, Lewington, A J P, Li, W, Liesner, R, Linger, R J, Liu, B, Longhurst, H, Lorenzo, L E, Louka, E, Hadeler, S L, Lyons, P A, Macdougall, M, Machado, R D, MacKenzie Ross, R V, Mackillop, L H, MacLaren, R, Madan, B, Magee, L, Mahdi-Rogers, M, Maher, E R, Maimaris, J, Makris, M, Mangles, S, Manson, A, Manzur, A, Mapeta, R, Marchbank, K J, Mark, P B, Marks, S, Markus, H S, Marschall, H U, Marshall, A, Martin, J M, Masati, L, Mathias, M, Matser, V, Matthews, E L, Maw, A, Maxwell, H, McAlinden, P, McCarthy, M I, McDermott, E M, McGowan, S J, McJannet, C, McKinney, H, Meacham, S, Mead, A J, Castello, I M, Meehan, S, Megy, K, Mehta, S, Mercer, C L, Michaelides, M, Michell, A C, Milford, D, Millar, C M, Millar, H, Mistry, A, Moenen, F, Moledina, S, Montani, D, Moore, A T, Moore, J, Morrell, N W, Morrisson, V, Mozere, M, Muir, K W, Mumford, A D, Murng, S H K, Nasir, I, Nejentsev, S, Newnham, M, Ng, J, Ngoh, A, Noorani, S, Noori, M, Nurden, P, O’Sullivan, J M, Obaji, S, Okoli, S, Oksenhendler, E, Olschewski, A, Olschewski, H, Ong, A C M, Ong, K R, Oram, H, Ormondroyd, E, Othman, S, Ouwehand, W H, Pantazis, A, Papadia, S, Papandreou, A, Park, S M, Parker, A P J, Parry, D, Parsons, G, Pasi, K J, Paterson, J, Payne, J H, Peacock, A J, Peerlinck, K, Penkett, C J, Pepke-Zaba, J, Perry, D, Petersen, R, Piechowski-Jozwiak, B, Pinto, F, Polwarth, G J, Ponsford, M J, Prasad, S, Prokopenko, I, Psaila, B, Pyle, A, Qasim, W, Quinn, E, Quinti, I, Raina, S, Ranganathan, L, Rankin, J, Rankin, S, Rao, A, Raymond, F L, Rayner-Matthews, P J, Rehnstrom, K, Reid, E, Reilly, M M, Renton, T, Revel-Vilk, S, Rhodes, C J, Rice, A S C, Richards, E E, Richards, M, Richardson, S, Richter, A, Robert, L, Roberts, I, Rondina, M T, Rosser, E, Rothwell, P, Roughley, C, Roy, N B, Rue-Albrecht, K, Sadeghi-Alavijeh, O, Saleem, M A, Salmon, R M, Samani, N J, Samarghitean, C, Sambrook, J G, Sanchis-Juan, A, Sandford, R, Santra, S, Sargur, R B, Satchell, S C, Savic, S, Scelsi, L, Schotte, G, Schulman, S, Schulze, H, Scott, R, Scully, M, Searle, C, Seeger, W, Seneviratne, S L, Sewell, W A C, Seyres, D, Shackley, F, Shamardina, O, Shapiro, S E, Sharma, P, Shehata, H A, Shipley, D, Shtoyerman, R, Sibson, K, Side, L, Simeoni, I, Simpson, M, Sims, M C, Sinha, M D, Sivapalaratnam, S, Skytte, A B, Smith, K G C, Snape, K, Sneddon, L, Sohal, A, Soubrier, F, Southgate, L, Southwood, M, Splitt, M, Staines, S, Staples, E, Stark, H, Stauss, H, Steele, C L, Stein, D, Stein, P E, Stephens, J, Stirrups, K E, Stock, S, Stubbs, M J, Suntharalingam, J, Swietlik, E M, Symington, E, Tait, R C, Talks, K, Tan, R Y Y, Taylor, G B, Thachil, J, Thaventhiran, J E D, Themistocleous, A C, Thomas, D C, Thomas, E, 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Burns, S O, Kuijpers, T W, Turro, E, Ouwehand, W H, Thrasher, A J, Smith, K G C & Primary Immunodeficiency Consortium for the NIHR Bioresource 2020, ' Whole-genome sequencing of a sporadic primary immunodeficiency cohort ', Nature, vol. 583, no. 7814, pp. 90-95 . https://doi.org/10.1038/s41586-020-2265-1 Thaventhiran, J E D, Lango Allen, H, Burren, O S, Rae, W, Greene, D, Staples, E, Zhang, Z, Farmery, J H R, Simeoni, I, Rivers, E, Maimaris, J, Penkett, C J, Stephens, J, Deevi, S V V, Sanchis-Juan, A, Gleadall, N S, Thomas, M J, Sargur, R B, Gordins, P, Baxendale, H E, Brown, M, Tuijnenburg, P, Worth, A, Hanson, S, Linger, R J, Buckland, M S, Rayner-Matthews, P J, Gilmour, K C, Samarghitean, C, Seneviratne, S L, Sansom, D M, Lynch, A G, Megy, K, Ellinghaus, E, Ellinghaus, D, Jorgensen, S F, Karlsen, T H, Stirrups, K E, Cutler, A J, Kumararatne, D S, Chandra, A, Edgar, J D M, Herwadkar, A, Cooper, N, Grigoriadou, S, Huissoon, A P, Johnson, M, Thomas, D C, Wei, W & Primary Immunodeficiency Consortium for the NIHR Bioresource 2020, ' Whole-genome sequencing of a sporadic primary immunodeficiency cohort ', Nature, vol. 583, no. 7814, pp. 90-95 . https://doi.org/10.1038/s41586-020-2265-1 Nature |
ISSN: | 0028-0836 |
DOI: | 10.1038/s41586-020-2265-1 |
Popis: | Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2 and SOCS1 loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. Wellcome Trust, WT: 104807/Z/14/Z University College London, UCL: 100140/Z/12/Z, 107212/Z/15/Z, MR/L019027, 203141/Z/16/Z, 091157/Z/10/Z Bundesministerium für Bildung und Forschung, BMBF: 01ZX1306A University of Cambridge 201250/Z/16/Z 01ZX1709 Seventh Framework Programme, FP7 NIHR Bristol Biomedical Research Centre Deutsche Forschungsgemeinschaft, DFG Deutsche Forschungsgemeinschaft, DFG: EXC 2167-390884018 Juvenile Diabetes Research Foundation United Kingdom, JDRF: 9-2011-253, 5-SRA-2015-130-A-N National Institute for Health Research, NIHR: RG65966 Medical Research Council, MRC: RG95376, MR/L006197/1 Great Ormond Street Hospital for Children, GOSH Acknowledgements The NBR-RD PID Consortium is part of the NIHR BioResource, for which funding was provided by the NIHR (NIHR, grant number RG65966). We acknowledge the participation of all NIHR BioResource volunteers, and thank the NIHR BioResource centre and staff for their contribution. J.E.D.T. is supported by the Medical Research Council (MRC) (RG95376 and MR/L006197/1); A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; K.G.C.S. is supported by the MRC (programme grant MR/L019027) and is a Wellcome Investigator; A.J.C. was supported by the Wellcome Trust (091157/Z/10/Z, 107212/Z/15/Z, 100140/Z/12/Z, 203141/Z/16/Z), JDRF (9-2011-253, 5-SRA-2015-130-A-N), NIHR Oxford Biomedical Research Centre and NIHR Cambridge Biomedical Research Centre; E.E. has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement number 609020-Scientia Fellows; E.R. is supported by the Wellcome Trust (201250/Z/16/Z); D.E. is supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (SysInflame grant 01ZX1306A; GB-XMAP grant 01ZX1709) and funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) under Germany’s Excellence Strategy (EXC 2167-390884018). The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the NIHR. This research was co-funded by the support listed above and the NIHR Cambridge BRC. |
Databáze: | OpenAIRE |
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