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1. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections

Author

Borras, Silvia, Clark, Caroline, Dean, John, Miedzybrodzka, Zosia, Ross, Alison, Tennant, Stephen, Dabir, Tabib, Donnelly, Deirdre, Humphreys, Mervyn, Magee, Alex, McConnell, Vivienne, McKee, Shane, McNerlan, Susan, Morrison, Patrick J., Rea, Gillian, Stewart, Fiona, Cole, Trevor, Cooper, Nicola, Cooper-Charles, Lisa, Cox, Helen, Islam, Lily, Jarvis, Joanna, Keelagher, Rebecca, Lim, Derek, McMullan, Dominic, Morton, Jenny, Naik, Swati, O’Driscoll, Mary, Ong, Kai-Ren, Osio, Deborah, Ragge, Nicola, Turton, Sarah, Vogt, Julie, Williams, Denise, Bodek, Simon, Donaldson, Alan, Hills, Alison, Low, Karen, Newbury-Ecob, Ruth, Norman, Andrew M., Roberts, Eileen, Scurr, Ingrid, Smithson, Sarah, Tooley, Madeleine, Abbs, Steve, Armstrong, Ruth, Dunn, Carolyn, Holden, Simon, Park, Soo-Mi, Paterson, Joan, Raymond, Lucy, Reid, Evan, Sandford, Richard, Simonic, Ingrid, Tischkowitz, Marc, Woods, Geoff, Bradley, Lisa, Comerford, Joanne, Green, Andrew, Lynch, Sally, McQuaid, Shirley, Mullaney, Brendan, Berg, Jonathan, Goudie, David, Mavrak, Eleni, McLean, Joanne, McWilliam, Catherine, Reavey, Eleanor, Azam, Tara, Cleary, Elaine, Jackson, Andrew, Lam, Wayne, Lampe, Anne, Moore, David, Porteous, Mary, Baple, Emma, Baptista, Júlia, Brewer, Carole, Castle, Bruce, Kivuva, Emma, Owens, Martina, Rankin, Julia, Shaw-Smith, Charles, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Bradley, Therese, Davidson, Rosemarie, Gardiner, Carol, Joss, Shelagh, Kinning, Esther, Longman, Cheryl, McGowan, Ruth, Murday, Victoria, Pilz, Daniela, Tobias, Edward, Whiteford, Margo, Williams, Nicola, Barnicoat, Angela, Clement, Emma, Faravelli, Francesca, Hurst, Jane, Jenkins, Lucy, Jones, Wendy, Ajith Kumar, V.K., Lees, Melissa, Loughlin, Sam, Male, Alison, Morrogh, Deborah, Rosser, Elisabeth, Scott, Richard, Wilson, Louise, Beleza, Ana, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Irving, Melita, Izatt, Louise, Josifova, Dragana, Mohammed, Shehla, Molenda, Aneta, Robert, Leema, Roworth, Wendy, Ruddy, Deborah, Ryten, Mina, Yau, Shu, Bennett, Christopher, Blyth, Moira, Campbell, Jennifer, Coates, Andrea, Dobbie, Angus, Hewitt, Sarah, Hobson, Emma, Jackson, Eilidh, Jewell, Rosalyn, Kraus, Alison, Prescott, Katrina, Sheridan, Eamonn, Thomson, Jenny, Bradshaw, Kirsty, Dixit, Abhijit, Eason, Jacqueline, Haines, Rebecca, Harrison, Rachel, Mutch, Stacey, Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Sharif, Abid, Suri, Mohnish, Vasudevan, Pradeep, Canham, Natalie, Ellis, Ian, Greenhalgh, Lynn, Howard, Emma, Stinton, Victoria, Swale, Andrew, Weber, Astrid, Banka, Siddharth, Breen, Catherine, Briggs, Tracy, Burkitt-Wright, Emma, Chandler, Kate, Clayton-Smith, Jill, Donnai, Dian, Douzgou, Sofia, Gaunt, Lorraine, Jones, Elizabeth, Kerr, Bronwyn, Langley, Claire, Metcalfe, Kay, Smith, Audrey, Wright, Ronnie, Bourn, David, Burn, John, Fisher, Richard, Hellens, Steve, Henderson, Alex, Montgomery, Tara, Splitt, Miranda, Straub, Volker, Wright, Michael, Zwolinski, Simon, Allen, Zoe, Bernhard, Birgitta, Brady, Angela, Brooks, Claire, Busby, Louise, Clowes, Virginia, Ghali, Neeti, Holder, Susan, Ibitoye, Rita, Wakeling, Emma, Blair, Edward, Carmichael, Jenny, Cilliers, Deirdre, Clasper, Susan, Gibbons, Richard, Kini, Usha, Lester, Tracy, Nemeth, Andrea, Poulton, Joanna, Price, Sue, Shears, Debbie, Stewart, Helen, Wilkie, Andrew, Albaba, Shadi, Baker, Duncan, Balasubramanian, Meena, Johnson, Diana, Parker, Michael, Quarrell, Oliver, Stewart, Alison, Willoughby, Josh, Crosby, Charlene, Elmslie, Frances, Homfray, Tessa, Jin, Huilin, Lahiri, Nayana, Mansour, Sahar, Marks, Karen, McEntagart, Meriel, Saggar, Anand, Tatton-Brown, Kate, Butler, Rachel, Clarke, Angus, Corrin, Sian, Fry, Andrew, Kamath, Arveen, McCann, Emma, Mugalaasi, Hood, Pottinger, Caroline, Procter, Annie, Sampson, Julian, Sansbury, Francis, Varghese, Vinod, Baralle, Diana, Callaway, Alison, Cassidy, Emma J., Daniels, Stacey, Douglas, Andrew, Foulds, Nicola, Hunt, David, Kharbanda, Mira, Lachlan, Katherine, Mercer, Catherine, Side, Lucy, Temple, I. Karen, Wellesley, Diana, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., FurióTarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., MaleadyCrowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Acosta, Maria T., Adam, Margaret, Adams, David R., Agrawal, Pankaj B., Alejandro, Mercedes E., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dhar, Shweta U., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Douine, Emilie D., Draper, David D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Falk, Marni, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Findley, Laurie C., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Glass, Ian, Godfrey, Rena A., Golden-Grant, Katie, Goldman, Alica M., Goldstein, David B., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Gutierrez, Irma, Hahn, Sihoun, Hamid, Rizwan, Hanchard, Neil A., Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Johnston, Jean M., Karaviti, Lefkothea, Kelley, Emily G., Kennedy, Jennifer, Kiley, Dana, Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Krier, Joel B., Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Mak, Bryan, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McCormack, Colleen E., McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nakano-Okuno, Mariko, Nath, Avi, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Papp, Jeanette C., Parker, Neil H., Phillips, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Scott, C. Ron, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Sharma, Prashant, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Solnica-Krezel, Lilianna, Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tamburro, Cecelia P., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Wallace, Stephanie, Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-Kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Woods, Jeremy D., Yamamoto, Shinya, Yang, John, Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Jeffries, Lauren, Mis, Emily K., McWalter, Kirsty, Donkervoort, Sandra, Brodsky, Nina N., Carpier, Jean-Marie, Ji, Weizhen, Ionita, Cristian, Roy, Bhaskar, Morrow, Jon S., Darbinyan, Armine, Iyer, Krishna, Aul, Ritu B., Chao, Katherine R., Cobbold, Laura, Cohen, Stacey, Custodio, Helena M., Drummond-Borg, Margaret, Finanger, Erika, Hainline, Bryan E., Helbig, Ingo, Hewson, Stacy, Hu, Ying, Jackson, Adam, Konstantino, Monica, Leach, Meganne E., McCormick, David, Nelson, Stanley, Nguyen, Joanne, Nugent, Kimberly, Ortega, Lucy, Goodkin, Howard P., Roeder, Elizabeth, Roy, Sani, Sapp, Katie, Saade, Dimah, Sisodiya, Sanjay M., Stals, Karen, Towner, Shelley, Wilson, William, Khokha, Mustafa K., Bönnemann, Carsten G., Lucas, Carrie L., and Lakhani, Saquib A.

Published
2024
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2. Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis

Author

Ambrose, J.C., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de, Burca A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., Furió-Tarí, P., Hackett, J.M., Halai, D., Holman, J.E., Hubbard, T.J.P., Jackson, R., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., Maleady-Crowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Wood, S.M., Zarowiecki, M., Owen, Nicholas, Toms, Maria, Young, Rodrigo M., Eintracht, Jonathan, Sarkar, Hajrah, Brooks, Brian P., and Moosajee, Mariya

Published
2022
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3. Tools for exploring mouse models of human disease

Author

Haendel, M, Papatheodorou, I, Oellrich, A, Mungall, CJ, Washington, N, Lewis, SE, Robinson, PN, and Smedley, D

Subjects
Networking and Information Technology R&D, Biotechnology, Genetics, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Neurology & Neurosurgery, Neurosciences, Pharmacology and Pharmaceutical Sciences
Abstract

Despite significant computational challenges, a number of tools have been developed recently to leverage the mouse to model human disease. Here we review these tools and show how they can be applied in the identification of candidate genes and therapeutic targets as well as mouse models for mechanistic studies and drug validation.

Published
2016

4. Genome wide conditional mouse knockout resources

Author

Kaloff, C, Anastassiadis, K, Ayadi, A, Baldock, R, Beig, J, Birling, M-C, Bradley, A, Brown, SDM, Bürger, A, Bushell, W, Chiani, F, Collins, FS, Doe, B, Eppig, JT, Finnell, RH, Fletcher, C, Flicek, P, Fray, M, Friedel, RH, Gambadoro, A, Gates, H, Hansen, J, Herault, Y, Hicks, GG, Hörlein, A, de Angelis, M Hrabé, Iyer, V, de Jong, PJ, Koscielny, G, Kühn, R, Liu, P, Lloyd, KCK, Lopez, RG, Marschall, S, Martínez, S, McKerlie, C, Meehan, T, von Melchner, H, Moore, M, Murray, SA, Nagy, A, Nutter, LMJ, Pavlovic, G, Pombero, A, Prosser, H, Ramirez-Solis, R, Ringwald, M, Rosen, B, Rosenthal, N, Rossant, J, Noppinger, P Ruiz, Ryder, E, Skarnes, WC, Schick, J, Schnütgen, F, Schofield, P, Seisenberger, C, Selloum, M, Smedley, D, Simpson, EM, Stewart, AF, Teboul, L, Valentini, GP Tocchini, Valenzuela, D, West, AP, and Wurst, W

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Biotechnology, Genetics, Stem Cell Research - Embryonic - Non-Human, Stem Cell Research, Human Genome, 2.6 Resources and infrastructure (aetiology), Generic health relevance, Neurosciences, Neurology & Neurosurgery, Pharmacology and pharmaceutical sciences
Abstract

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6,000 mutant mouse strains have been produced by the IKMC and mostly the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 inducible cre-driver mouse strains in a C57BL/6 background. Complementing the cre-driver resource, a collection of comprising 27 cre-driver rAAVs has also been produced. The resources can be easily accessed at the IKMC/IMPC web portal (www.mousephenotype.org). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds that enables the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research.

Published
2016

5. Biallelic CRELD1 variants cause a multisystem syndrome including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections.

Author

Jeffries, Lauren, primary, Mis, Emily K., additional, McWalter, Kirsty, additional, Donkervoort, Sandra, additional, Brodsky, Nina N., additional, Carpier, Jean-Marie, additional, Ji, Weizhen, additional, Ionita, Cristian, additional, Roy, Bhaskar, additional, Morrow, Jon S., additional, Darbinyan, Armine, additional, Iyer, Krishna, additional, Aul, Ritu B., additional, Banka, Siddharth, additional, Chao, Katherine R., additional, Cobbold, Laura, additional, Cohen, Stacey, additional, Custodio, Helena M., additional, Drummond-Borg, Margaret, additional, Elmslie, Frances, additional, Finanger, Erika, additional, Hainline, Bryan E., additional, Helbig, Ingo, additional, Hewson, Stacy, additional, Hu, Ying, additional, Jackson, Adam, additional, Josifova, Dragana, additional, Konstantino, Monica, additional, Leach, Meganne E., additional, Mak, Bryan, additional, McCormick, David, additional, McGee, Elisabeth, additional, Nelson, Stanley, additional, Nguyen, Joanne, additional, Nugent, Kimberly, additional, Ortega, Lucy, additional, Goodkin, Howard P., additional, Roeder, Elizabeth, additional, Roy, Sani, additional, Sapp, Katie, additional, Saade, Dimah, additional, Sisodiya, Sanjay M., additional, Stals, Karen, additional, Towner, Shelley, additional, Wilson, William, additional, Khokha, Mustafa K., additional, Bönnemann, Carsten G., additional, Lucas, Carrie L., additional, Lakhani, Saquib A., additional, Acosta, Maria T., additional, Adam, Margaret, additional, Adams, David R., additional, Agrawal, Pankaj B., additional, Alejandro, Mercedes E., additional, Alvey, Justin, additional, Amendola, Laura, additional, Andrews, Ashley, additional, Ashley, Euan A., additional, Azamian, Mahshid S., additional, Bacino, Carlos A., additional, Bademci, Guney, additional, Baker, Eva, additional, Balasubramanyam, Ashok, additional, Baldridge, Dustin, additional, Bale, Jim, additional, Bamshad, Michael, additional, Barbouth, Deborah, additional, Bayrak-Toydemir, Pinar, additional, Beck, Anita, additional, Beggs, Alan H., additional, Behrens, Edward, additional, Bejerano, Gill, additional, Bennet, Jimmy, additional, Berg-Rood, Beverly, additional, Bernstein, Jonathan A., additional, Berry, Gerard T., additional, Bican, Anna, additional, Bivona, Stephanie, additional, Blue, Elizabeth, additional, Bohnsack, John, additional, Bonnenmann, Carsten, additional, Bonner, Devon, additional, Botto, Lorenzo, additional, Boyd, Brenna, additional, Briere, Lauren C., additional, Brokamp, Elly, additional, Brown, Gabrielle, additional, Burke, Elizabeth A., additional, Burrage, Lindsay C., additional, Butte, Manish J., additional, Byers, Peter, additional, Byrd, William E., additional, Carey, John, additional, Carrasquillo, Olveen, additional, Peter Chang, Ta Chen, additional, Chanprasert, Sirisak, additional, Chao, Hsiao-Tuan, additional, Clark, Gary D., additional, Coakley, Terra R., additional, Cobban, Laurel A., additional, Cogan, Joy D., additional, Coggins, Matthew, additional, Cole, F Sessions, additional, Colley, Heather A., additional, Cooper, Cynthia M., additional, Craigen, William J., additional, Crouse, Andrew B., additional, Cunningham, Michael, additional, D'Souza, Precilla, additional, Dai, Hongzheng, additional, Dasari, Surendra, additional, Davids, Mariska, additional, Dayal, Jyoti G., additional, Deardorff, Matthew, additional, Dell'Angelica, Esteban C., additional, Dhar, Shweta U., additional, Dipple, Katrina, additional, Doherty, Daniel, additional, Dorrani, Naghmeh, additional, Douine, Emilie D., additional, Draper, David D., additional, Duncan, Laura, additional, Earl, Dawn, additional, Eckstein, David J., additional, Emrick, Lisa T., additional, Eng, Christine M., additional, Esteves, Cecilia, additional, Estwick, Tyra, additional, Falk, Marni, additional, Fernandez, Liliana, additional, Ferreira, Carlos, additional, Fieg, Elizabeth L., additional, Findley, Laurie C., additional, Fisher, Paul G., additional, Fogel, Brent L., additional, Forghani, Irman, additional, Fresard, Laure, additional, Gahl, William A., additional, Glass, Ian, additional, Godfrey, Rena A., additional, Golden-Grant, Katie, additional, Goldman, Alica M., additional, Goldstein, David B., additional, Grajewski, Alana, additional, Groden, Catherine A., additional, Gropman, Andrea L., additional, Gutierrez, Irma, additional, Hahn, Sihoun, additional, Hamid, Rizwan, additional, Hanchard, Neil A., additional, Hassey, Kelly, additional, Hayes, Nichole, additional, High, Frances, additional, Hing, Anne, additional, Hisama, Fuki M., additional, Holm, Ingrid A., additional, Hom, Jason, additional, Horike-Pyne, Martha, additional, Huang, Alden, additional, Huang, Yong, additional, Isasi, Rosario, additional, Jamal, Fariha, additional, Jarvik, Gail P., additional, Jarvik, Jeffrey, additional, Jayadev, Suman, additional, Johnston, Jean M., additional, Karaviti, Lefkothea, additional, Kelley, Emily G., additional, Kennedy, Jennifer, additional, Kiley, Dana, additional, Kohane, Isaac S., additional, Kohler, Jennefer N., additional, Krakow, Deborah, additional, Krasnewich, Donna M., additional, Kravets, Elijah, additional, Korrick, Susan, additional, Koziura, Mary, additional, Krier, Joel B., additional, Lalani, Seema R., additional, Lam, Byron, additional, Lam, Christina, additional, Lanpher, Brendan C., additional, Lanza, Ian R., additional, Lau, C Christopher, additional, LeBlanc, Kimberly, additional, Lee, Brendan H., additional, Lee, Hane, additional, Levitt, Roy, additional, Lewis, Richard A., additional, Lincoln, Sharyn A., additional, Liu, Pengfei, additional, Liu, Xue Zhong, additional, Longo, Nicola, additional, Loo, Sandra K., additional, Loscalzo, Joseph, additional, Maas, Richard L., additional, Macnamara, Ellen F., additional, MacRae, Calum A., additional, Maduro, Valerie V., additional, Majcherska, Marta M., additional, Christine V Malicdan, May, additional, Mamounas, Laura A., additional, Manolio, Teri A., additional, Mao, Rong, additional, Maravilla, Kenneth, additional, Markello, Thomas C., additional, Marom, Ronit, additional, Marth, Gabor, additional, Martin, Beth A., additional, Martin, Martin G., additional, Martínez-Agosto, Julian A., additional, Marwaha, Shruti, additional, McCauley, Jacob, additional, McCormack, Colleen E., additional, McCray, Alexa T., additional, Mefford, Heather, additional, Merritt, J Lawrence, additional, Might, Matthew, additional, Mirzaa, Ghayda, additional, Morava, Eva, additional, Moretti, Paolo M., additional, Morimoto, Marie, additional, Mulvihill, John J., additional, Murdock, David R., additional, Nakano-Okuno, Mariko, additional, Nath, Avi, additional, Nelson, Stan F., additional, Newman, John H., additional, Nicholas, Sarah K., additional, Nickerson, Deborah, additional, Nieves-Rodriguez, Shirley, additional, Novacic, Donna, additional, Oglesbee, Devin, additional, Orengo, James P., additional, Pace, Laura, additional, Pak, Stephen, additional, Pallais, J Carl, additional, Papp, Jeanette C., additional, Parker, Neil H., additional, Phillips, John A., additional, Posey, Jennifer E., additional, Potocki, Lorraine, additional, Pusey, Barbara N., additional, Quinlan, Aaron, additional, Raskind, Wendy, additional, Raja, Archana N., additional, Rao, Deepak A., additional, Renteria, Genecee, additional, Reuter, Chloe M., additional, Rives, Lynette, additional, Robertson, Amy K., additional, Rodan, Lance H., additional, Rosenfeld, Jill A., additional, Rosenwasser, Natalie, additional, Ruzhnikov, Maura, additional, Sacco, Ralph, additional, Sampson, Jacinda B., additional, Samson, Susan L., additional, Saporta, Mario, additional, Scott, C Ron, additional, Schaechter, Judy, additional, Schedl, Timothy, additional, Scott, Daryl A., additional, Sharma, Prashant, additional, Shin, Jimann, additional, Signer, Rebecca, additional, Sillari, Catherine H., additional, Silverman, Edwin K., additional, Sinsheimer, Janet S., additional, Sisco, Kathy, additional, Smith, Edward C., additional, Smith, Kevin S., additional, Solem, Emily, additional, Solnica-Krezel, Lilianna, additional, Stoler, Joan M., additional, Stong, Nicholas, additional, Sullivan, Jennifer A., additional, Sun, Angela, additional, Sutton, Shirley, additional, Sweetser, David A., additional, Sybert, Virginia, additional, Tabor, Holly K., additional, Tamburro, Cecelia P., additional, Tekin, Mustafa, additional, Telischi, Fred, additional, Thorson, Willa, additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Tran, Alyssa A., additional, Tucker, Brianna M., additional, Urv, Tiina K., additional, Vanderver, Adeline, additional, Velinder, Matt, additional, Viskochil, Dave, additional, Vogel, Tiphanie P., additional, Wahl, Colleen E., additional, Wallace, Stephanie, additional, Walley, Nicole M., additional, Walsh, Chris A., additional, Walker, Melissa, additional, Wambach, Jennifer, additional, Wan, Jijun, additional, Wang, Lee-Kai, additional, Wangler, Michael F., additional, Ward, Patricia A., additional, Wegner, Daniel, additional, Wener, Mark, additional, Wenger, Tara, additional, Perry, Katherine Wesseling, additional, Westerfield, Monte, additional, Wheeler, Matthew T., additional, Whitlock, Jordan, additional, Wolfe, Lynne A., additional, Woods, Jeremy D., additional, Yamamoto, Shinya, additional, Yang, John, additional, Yu, Guoyun, additional, Zastrow, Diane B., additional, Zhao, Chunli, additional, Zuchner, Stephan, additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, FurióTarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, MaleadyCrowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, and Witkowska, K., additional

Published
2023
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8. Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia

Author

Morsy, Heba, primary, Benkirane, Mehdi, additional, Cali, Elisa, additional, Rocca, Clarissa, additional, Zhelcheska, Kristina, additional, Cipriani, Valentina, additional, Galanaki, Evangelia, additional, Maroofian, Reza, additional, Efthymiou, Stephanie, additional, Murphy, David, additional, O’Driscoll, Mary, additional, Suri, Mohnish, additional, Banka, Siddharth, additional, Clayton-Smith, Jill, additional, Wright, Thomas, additional, Redman, Melody, additional, Bassetti, Jennifer A., additional, Nizon, Mathilde, additional, Cogne, Benjamin, additional, Jamra, Rami Abu, additional, Bartolomaeus, Tobias, additional, Heruth, Marion, additional, Krey, Ilona, additional, Gburek-Augustat, Janina, additional, Wieczorek, Dagmar, additional, Gattermann, Felix, additional, Mcentagart, Meriel, additional, Goldenberg, Alice, additional, Guyant-Marechal, Lucie, additional, Garcia-Moreno, Hector, additional, Giunti, Paola, additional, Chabrol, Brigitte, additional, Bacrot, Severine, additional, Buissonnière, Roger, additional, Magry, Virginie, additional, Gowda, Vykuntaraju K., additional, Srinivasan, Varunvenkat M., additional, Melegh, Béla, additional, Szabó, András, additional, Sümegi, Katalin, additional, Cossée, Mireille, additional, Ziff, Monica, additional, Butterfield, Russell, additional, Hunt, David, additional, Bird-Lieberman, Georgina, additional, Hanna, Michael, additional, Koenig, Michel, additional, Stankewich, Michael, additional, Vandrovcova, Jana, additional, Houlden, Henry, additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Brittain, H., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, and Zarowiecki, M., additional

Published
2023
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9. Genome wide conditional mouse knockout resources

Author

Kaloff, C., Anastassiadis, K., Ayadi, A., Baldock, R., Beig, J., Birling, M.-C., Bradley, A., Brown, S.D.M., Bürger, A., Bushell, W., Chiani, F., Collins, F.S., Doe, B., Eppig, J.T., Finnell, R.H., Fletcher, C., Flicek, P., Fray, M., Friedel, R.H., Gambadoro, A., Gates, H., Hansen, J., Herault, Y., Hicks, G.G., Hörlein, A., Hrabé de Angelis, M., Iyer, V., de Jong, P.J., Koscielny, G., Kühn, R., Liu, P., Lloyd, K.C.K, Lopez, R.G., Marschall, S., Martínez, S., McKerlie, C., Meehan, T., von Melchner, H., Moore, M., Murray, S.A., Nagy, A., Nutter, L.M.J., Pavlovic, G., Pombero, A., Prosser, H., Ramirez-Solis, R., Ringwald, M., Rosen, B., Rosenthal, N., Rossant, J., Ruiz Noppinger, P., Ryder, E., Skarnes, W.C., Schick, J., Schnütgen, F., Schofield, P., Seisenberger, C., Selloum, M., Smedley, D., Simpson, E.M., Stewart, A.F., Teboul, L., Tocchini Valentini, G.P., Valenzuela, D., West, A.P., and Wurst, W.

Published
2016
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10. Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy

Author

Park, Joohyun, primary, Tucci, Arianna, additional, Cipriani, Valentina, additional, Demidov, German, additional, Rocca, Clarissa, additional, Senderek, Jan, additional, Butryn, Michaela, additional, Velic, Ana, additional, Lam, Tanya, additional, Galanaki, Evangelia, additional, Cali, Elisa, additional, Vestito, Letizia, additional, Maroofian, Reza, additional, Deininger, Natalie, additional, Rautenberg, Maren, additional, Admard, Jakob, additional, Hahn, Gesa-Astrid, additional, Bartels, Claudius, additional, van Os, Nienke J.H., additional, Horvath, Rita, additional, Chinnery, Patrick F., additional, Tiet, May Yung, additional, Hewamadduma, Channa, additional, Hadjivassiliou, Marios, additional, Tofaris, George K., additional, Wood, Nicholas W., additional, Hayer, Stefanie N., additional, Bender, Friedemann, additional, Menden, Benita, additional, Cordts, Isabell, additional, Klein, Katrin, additional, Nguyen, Huu Phuc, additional, Krauss, Joachim K., additional, Blahak, Christian, additional, Strom, Tim M., additional, Sturm, Marc, additional, van de Warrenburg, Bart, additional, Lerche, Holger, additional, Maček, Boris, additional, Synofzik, Matthis, additional, Ossowski, Stephan, additional, Timmann, Dagmar, additional, Wolf, Marc E., additional, Smedley, Damian, additional, Riess, Olaf, additional, Schöls, Ludger, additional, Houlden, Henry, additional, Haack, Tobias B., additional, Hengel, Holger, additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Brittain, H., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, and Zarowiecki, M., additional

Published
2022
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11. Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism

Author

Chopra, M., McEntagart, M., Clayton-Smith, J., Platzer, K., Shukla, A., Girisha, K.M., Kaur, A., Kaur, P., Pfundt, R., Veenstra-Knol, H., Mancini, G.M.S., Cappuccio, G., Brunetti-Pierri, N., Kortum, F., Hempel, M., Denecke, J., Lehman, A., Kleefstra, T., Stuurman, K.E., Wilke, M., Thompson, M.L., Bebin, E.M., Bijlsma, E.K., Hoffer, M.J.V., Peeters-Scholte, C., Slavotinek, A., Weiss, W.A., Yip, T., Hodoglugil, U., Whittle, A., Monda, J., Neira, J., Yang, S., Kirby, A., Pinz, H., Lechner, R., Sleutels, F., Helbig, I., McKeown, S., Helbig, K., Willaert, R., Juusola, J., Semotok, J., Hadonou, M., Short, J., Yachelevich, N., Lala, S., Fernandez-Jaen, A., Pelayo, J.P., Klockner, C., Kamphausen, S.B., Abou Jamra, R., Arelin, M., Innes, A.M., Niskakoski, A., Amin, S., Williams, M., Evans, J., Smithson, S., Smedley, D., Burca, A., Kini, U., Delatycki, M.B., Gallacher, L., Yeung, A., Pais, L., Field, M., Martin, E., Charles, P., Courtin, T., Keren, B., Iascone, M., Cereda, A., Poke, G., Abadie, V., Chalouhi, C., Parthasarathy, P., Halliday, B.J., Robertson, S.P., Lyonnet, S., Amiel, J., Gordon, C.T., CAUSES Study, Genomics England Res Consortium, Clinical Genetics, Chopra, Maya, Mcentagart, Meriel, Clayton-Smith, Jill, Platzer, Konrad, Shukla, Anju, Girisha, Katta M, Kaur, Anupriya, Kaur, Parneet, Pfundt, Rolph, Veenstra-Knol, Hermine, Mancini, Grazia M S, Cappuccio, Gerarda, Brunetti-Pierri, Nicola, Kortüm, Fanny, Hempel, Maja, Denecke, Jona, Lehman, Anna, Kleefstra, Tjitske, Stuurman, Kyra E, Wilke, Martina, Thompson, Michelle L, Bebin, E Martina, Bijlsma, Emilia K, Hoffer, Mariette J V, Peeters-Scholte, Cacha, Slavotinek, Anne, Weiss, William A, Yip, Tiffany, Hodoglugil, Ugur, Whittle, Amy, Dimonda, Janette, Neira, Juanita, Yang, Sandra, Kirby, Amelia, Pinz, Hailey, Lechner, Rosan, Sleutels, Frank, Helbig, Ingo, Mckeown, Sarah, Helbig, Katherine, Willaert, Rebecca, Juusola, Jane, Semotok, Jennifer, Hadonou, Medard, Short, John, Yachelevich, Naomi, Lala, Sajel, Fernández-Jaen, Alberto, Pelayo, Janvier Porta, Klöckner, Chiara, Kamphausen, Susanne B, Abou Jamra, Rami, Arelin, Maria, Innes, A Micheil, Niskakoski, Anni, Amin, Sam, Williams, Maggie, Evans, Julie, Smithson, Sarah, Smedley, Damian, de Burca, Anna, Kini, Usha, Delatycki, Martin B, Gallacher, Lyndon, Yeung, Alison, Pais, Lynn, Field, Michael, Martin, Ellenore, Charles, Perrine, Courtin, Thoma, Keren, Bori, Iascone, Maria, Cereda, Anna, Poke, Gemma, Abadie, Véronique, Chalouhi, Christel, Parthasarathy, Padmini, Halliday, Benjamin J, Robertson, Stephen P, Lyonnet, Stanisla, Amiel, Jeanne, and Gordon, Christopher T

Subjects
Male, speech delay, Haploinsufficiency, Craniofacial Abnormalities, 0302 clinical medicine, Neurodevelopmental disorder, Loss of Function Mutation, Intellectual disability, Missense mutation, Ankyrin, Child, Genetics (clinical), Genetics, chemistry.chemical_classification, 0303 health sciences, RNA-Binding Proteins, Syndrome, Pedigree, ANKYRIN REPEAT, Phenotype, Child, Preschool, Speech delay, Female, medicine.symptom, Signal Transduction, Adult, Heterozygote, Adolescent, MASK, ANKRD17, dysmorphism, Biology, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Intellectual Disability, Report, medicine, Humans, Language Development Disorders, Yorkie, Loss function, 030304 developmental biology, HIPPO PATHWAY, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MUTATIONS, Infant, medicine.disease, GENE, neurodevelopmental syndrome, chemistry, Ankyrin repeat, 030217 neurology & neurosurgery
Abstract

ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.

Published
2021

12. Genotype–phenotype correlations for COL4A3–COL4A5 variants resulting in Gly substitutions in Alport syndrome

Author

Gibson, Joel T., Huang, Mary, Shenelli Croos Dabrera, Marina, Shukla, Krushnam, Rothe, Hansjörg, Hilbert, Pascale, Deltas, Constantinos, Storey, Helen, Lipska-Ziętkiewicz, Beata S., Chan, Melanie M. Y., Sadeghi-Alavijeh, Omid, Gale, Daniel P., Ambrose, J. C., Arumugam, P., Baple, E. L., Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Giess, A., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Kousathanas, A., Lahnstein, L., Lawson, K., Leigh, S. E. A., Leong, I. U. S., Lopez, F. J., Maleady-Crowe, F., Mason, J., McDonagh, E. M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., Odhams, C. A., Orioli, A., Patch, C., Perez-Gil, D., Pereira, M. B., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R. H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K. R., Smith, S. C., Sosinsky, A., Spooner, W., Stevens, H. E., Stuckey, A., Sultana, R., Tanguy, M., Thomas, E. R. A., Thompson, S. R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S. A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Cerkauskaite, Agne, and Savige, Judy

Subjects
Multidisciplinary, otorhinolaryngologic diseases, urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

Alport syndrome is the commonest inherited kidney disease and nearly half the pathogenic variants in the COL4A3–COL4A5 genes that cause Alport syndrome result in Gly substitutions. This study examined the molecular characteristics of Gly substitutions that determine the severity of clinical features. Pathogenic COL4A5 variants affecting Gly in the Leiden Open Variation Database in males with X-linked Alport syndrome were correlated with age at kidney failure (n = 157) and hearing loss diagnosis (n = 80). Heterozygous pathogenic COL4A3 and COL4A4 variants affecting Gly (n = 304) in autosomal dominant Alport syndrome were correlated with the risk of haematuria in the UK 100,000 Genomes Project. Gly substitutions were stratified by exon location (1 to 20 or 21 to carboxyl terminus), being adjacent to a non-collagenous region (interruption or terminus), and the degree of instability caused by the replacement residue. Pathogenic COL4A5 variants that resulted in a Gly substitution with a highly destabilising residue reduced the median age at kidney failure by 7 years (p = 0.002), and age at hearing loss diagnosis by 21 years (p = 0.004). Substitutions adjacent to a non-collagenous region delayed kidney failure by 19 years (p = 0.014). Heterozygous pathogenic COL4A3 and COL4A4 variants that resulted in a Gly substitution with a highly destabilising residue (Arg, Val, Glu, Asp, Trp) were associated with an increased risk of haematuria (p = 0.018), and those adjacent to a non-collagenous region were associated with a reduced risk (p = 0.046). Exon location had no effect. In addition, COL4A5 variants adjacent to non-collagenous regions were over-represented in the normal population in gnomAD (p

Published
2022

13. Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis

Author

Owen, Nicholas, primary, Toms, Maria, additional, Young, Rodrigo M., additional, Eintracht, Jonathan, additional, Sarkar, Hajrah, additional, Brooks, Brian P., additional, Moosajee, Mariya, additional, Ambrose, J.C., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de, Burca A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Jackson, R., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, and Zarowiecki, M., additional

Published
2022
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14. Expanding SPTAN1monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia

Author

Morsy, Heba, Benkirane, Mehdi, Cali, Elisa, Rocca, Clarissa, Zhelcheska, Kristina, Cipriani, Valentina, Galanaki, Evangelia, Maroofian, Reza, Efthymiou, Stephanie, Murphy, David, O’Driscoll, Mary, Suri, Mohnish, Banka, Siddharth, Clayton-Smith, Jill, Wright, Thomas, Redman, Melody, Bassetti, Jennifer A., Nizon, Mathilde, Cogne, Benjamin, Jamra, Rami Abu, Bartolomaeus, Tobias, Heruth, Marion, Krey, Ilona, Gburek-Augustat, Janina, Wieczorek, Dagmar, Gattermann, Felix, Mcentagart, Meriel, Goldenberg, Alice, Guyant-Marechal, Lucie, Garcia-Moreno, Hector, Giunti, Paola, Chabrol, Brigitte, Bacrot, Severine, Buissonnière, Roger, Magry, Virginie, Gowda, Vykuntaraju K., Srinivasan, Varunvenkat M., Melegh, Béla, Szabó, András, Sümegi, Katalin, Cossée, Mireille, Ziff, Monica, Butterfield, Russell, Hunt, David, Bird-Lieberman, Georgina, Hanna, Michael, Koenig, Michel, Stankewich, Michael, Vandrovcova, Jana, Houlden, Henry, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Brittain, H., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., Furió-Tarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., Maleady-Crowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Wood, S.M., and Zarowiecki, M.

Abstract

Nonerythrocytic αII-spectrin (SPTAN1) variants have been previously associated with intellectual disability and epilepsy. We conducted this study to delineate the phenotypic spectrum of SPTAN1variants.

Published
2023
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16. Heterozygous UCHL1loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy

Author

Park, Joohyun, Tucci, Arianna, Cipriani, Valentina, Demidov, German, Rocca, Clarissa, Senderek, Jan, Butryn, Michaela, Velic, Ana, Lam, Tanya, Galanaki, Evangelia, Cali, Elisa, Vestito, Letizia, Maroofian, Reza, Deininger, Natalie, Rautenberg, Maren, Admard, Jakob, Hahn, Gesa-Astrid, Bartels, Claudius, van Os, Nienke J.H., Horvath, Rita, Chinnery, Patrick F., Tiet, May Yung, Hewamadduma, Channa, Hadjivassiliou, Marios, Tofaris, George K., Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Brittain, H., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., Furió-Tarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., Maleady-Crowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Wood, S.M., Zarowiecki, M., Wood, Nicholas W., Hayer, Stefanie N., Bender, Friedemann, Menden, Benita, Cordts, Isabell, Klein, Katrin, Nguyen, Huu Phuc, Krauss, Joachim K., Blahak, Christian, Strom, Tim M., Sturm, Marc, van de Warrenburg, Bart, Lerche, Holger, Maček, Boris, Synofzik, Matthis, Ossowski, Stephan, Timmann, Dagmar, Wolf, Marc E., Smedley, Damian, Riess, Olaf, Schöls, Ludger, Houlden, Henry, Haack, Tobias B., and Hengel, Holger

Abstract

Biallelic variants in UCHL1have been associated with a progressive early-onset neurodegenerative disorder, autosomal recessive spastic paraplegia type 79. In this study, we investigated heterozygous UCHL1variants on the basis of results from cohort-based burden analyses.

Published
2022
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17. Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy

Author

Parry, David A., primary, Martin, Carol-Anne, additional, Greene, Philip, additional, Marsh, Joseph A., additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Brittain, H., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Giess, A., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Kousathanas, A., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Orioli, A., additional, Patch, C., additional, Perez-Gil, D., additional, Pereira, M.B., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Smith, S.C., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Tanguy, M., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, Zarowiecki, M., additional, Blyth, Moira, additional, Cox, Helen, additional, Donnelly, Deirdre, additional, Greenhalgh, Lynn, additional, Greville-Heygate, Stephanie, additional, Harrison, Victoria, additional, Lachlan, Katherine, additional, McKenna, Caoimhe, additional, Quigley, Alan J., additional, Rea, Gillian, additional, Robertson, Lisa, additional, Suri, Mohnish, additional, and Jackson, Andrew P., additional

Published
2021
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18. Ensembl 2008

Author

Flicek, P, Aken, BL, Beal, K, Ballester, B, Caccamo, M, Chen, Y, Clarke, L, Coates, G, Cunningham, F, Cutts, T, Down, T, Dyer, SC, Eyre, T, Fitzgerald, S, Fernandez-Banet, J, Gräf, S, Haider, S, Hammond, M, Holland, R, Howe, KL, Howe, K, Johnson, N, Jenkinson, A, Kähäri, A, Keefe, D, Kokocinski, F, Kulesha, E, Lawson, D, Longden, I, Megy, K, Meidl, P, Overduin, B, Parker, A, Pritchard, B, Prlic, A, Rice, S, Rios, D, Schuster, M, Sealy, I, Slater, G, Smedley, D, Spudich, G, Trevanion, S, Vilella, AJ, Vogel, J, White, S, Wood, M, Birney, E, Cox, T, Curwen, V, Durbin, R, Fernandez-Suarez, XM, Herrero, J, Hubbard, TJP, Kasprzyk, A, Proctor, G, Smith, J, Ureta-Vidal, A, and Searle, S

Subjects
Internet, Mice, User-Computer Interface, ComputingMethodologies_PATTERNRECOGNITION, Databases, Genetic, Computer Graphics, Animals, Humans, Genomics, Regulatory Elements, Transcriptional, Software
Abstract

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Published
2020
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20. DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

Author

Vig, Anjali, primary, Poulter, James A., additional, Ottaviani, Daniele, additional, Tavares, Erika, additional, Toropova, Katerina, additional, Tracewska, Anna Maria, additional, Mollica, Antonio, additional, Kang, Jasmine, additional, Kehelwathugoda, Oshini, additional, Paton, Tara, additional, Maynes, Jason T., additional, Wheway, Gabrielle, additional, Arno, Gavin, additional, Ambrose, J.C., additional, Arumugam, P., additional, Baple, E.L., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Brittain, H., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Hamblin, A., additional, Henderson, S., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Ibáñez, K., additional, Jackson, R., additional, Jones, L.J., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Murugaesu, N., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Riesgo-Ferreiro, P., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Sawant, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Sultana, R., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, Zarowiecki, M., additional, Khan, Kamron N., additional, McKibbin, Martin, additional, Toomes, Carmel, additional, Ali, Manir, additional, Di Scipio, Matteo, additional, Li, Shuning, additional, Ellingford, Jamie, additional, Black, Graeme, additional, Webster, Andrew, additional, Rydzanicz, Małgorzata, additional, Stawiński, Piotr, additional, Płoski, Rafał, additional, Vincent, Ajoy, additional, Cheetham, Michael E., additional, Inglehearn, Chris F., additional, Roberts, Anthony, additional, and Heon, Elise, additional

Published
2020
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21. De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas

Author

Tolchin, Dara, primary, Yeager, Jessica P., additional, Prasad, Priya, additional, Dorrani, Naghmeh, additional, Russi, Alvaro Serrano, additional, Martinez-Agosto, Julian A., additional, Haseeb, Abdul, additional, Angelozzi, Marco, additional, Santen, G.W.E., additional, Ruivenkamp, Claudia, additional, Mercimek-Andrews, Saadet, additional, Depienne, Christel, additional, Kuechler, Alma, additional, Mikat, Barbara, additional, Ludecke, Hermann-Josef, additional, Bilan, Frederic, additional, Le Guyader, Gwenael, additional, Gilbert-Dussardier, Brigitte, additional, Keren, Boris, additional, Heide, Solveig, additional, Haye, Damien, additional, Van Esch, Hilde, additional, Keldermans, Liesbeth, additional, Ortiz, Damara, additional, Lancaster, Emily, additional, Krantz, Ian D., additional, Krock, Bryan L., additional, Pechter, Kieran B., additional, Arkader, Alexandre, additional, Medne, Livija, additional, DeChene, Elizabeth T., additional, Calpena, Eduardo, additional, Melistaccio, Giada, additional, Wilkie, Andrew O.M., additional, Suri, Mohnish, additional, Foulds, Nicola, additional, Begtrup, Amber, additional, Henderson, Lindsay B., additional, Forster, Cara, additional, Reed, Patrick, additional, McDonald, Marie T., additional, McConkie-Rosell, Allyn, additional, Thevenon, Julien, additional, Le Tanno, Pauline, additional, Coutton, Charles, additional, Tsai, Anne C.H., additional, Stewart, Sarah, additional, Maver, Ales, additional, Gorazd, Rudolf, additional, Pichon, Olivier, additional, Nizon, Mathilde, additional, Cogné, Benjamin, additional, Isidor, Bertrand, additional, Martin-Coignard, Dominique, additional, Stoeva, Radka, additional, Lefebvre, Véronique, additional, Le Caignec, Cédric, additional, Ambrose, J.C., additional, Bleda, M., additional, Boardman-Pretty, F., additional, Boissiere, J.M., additional, Boustred, C.R., additional, Caulfield, M.J., additional, Chan, G.C., additional, Craig, C.E.H., additional, Daugherty, L.C., additional, de Burca, A., additional, Devereau, A., additional, Elgar, G., additional, Foulger, R.E., additional, Fowler, T., additional, Furió-Tarí, P., additional, Hackett, J.M., additional, Halai, D., additional, Holman, J.E., additional, Hubbard, T.J.P., additional, Kasperaviciute, D., additional, Kayikci, M., additional, Lahnstein, L., additional, Lawson, K., additional, Leigh, S.E.A., additional, Leong, I.U.S., additional, Lopez, F.J., additional, Maleady-Crowe, F., additional, Mason, J., additional, McDonagh, E.M., additional, Moutsianas, L., additional, Mueller, M., additional, Need, A.C., additional, Odhams, C.A., additional, Patch, C., additional, Perez-Gil, D., additional, Polychronopoulos, D., additional, Pullinger, J., additional, Rahim, T., additional, Rendon, A., additional, Rogers, T., additional, Ryten, M., additional, Savage, K., additional, Scott, R.H., additional, Siddiq, A., additional, Sieghart, A., additional, Smedley, D., additional, Smith, K.R., additional, Sosinsky, A., additional, Spooner, W., additional, Stevens, H.E., additional, Stuckey, A., additional, Thomas, E.R.A., additional, Thompson, S.R., additional, Tregidgo, C., additional, Tucci, A., additional, Walsh, E., additional, Watters, S.A., additional, Welland, M.J., additional, Williams, E., additional, Witkowska, K., additional, Wood, S.M., additional, and Zarowiecki, M., additional

Published
2020
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22. Ensembl 2009

Author

Hubbard, T. J. P., Aken, B. L., Ayling, S., Ballester, B., Beal, K., Bragin, E., Brent, S., Chen, Y., Clapham, P., Clarke, L., Coates, G., Fairley, S., Fitzgerald, S., Fernandez-Banet, J., Gordon, L., Graf, S., Haider, S., Hammond, M., Holland, R., Howe, K., Jenkinson, A., Johnson, N., Kahari, A., Keefe, D., Keenan, S., Kinsella, R., Kokocinski, F., Kulesha, E., Lawson, D., Longden, I., Megy, K., Meidl, P., Overduin, B., Parker, A., Pritchard, B., Rios, D., Schuster, M., Slater, G., Smedley, D., Spooner, W., Spudich, G., Trevanion, S., Vilella, A., Vogel, J., White, S., Wilder, S., Zadissa, A., Birney, E., Cunningham, F., Curwen, V., Durbin, R., Fernandez-Suarez, X. M., Herrero, J., Kasprzyk, A., Proctor, G., Smith, J., Searle, S., and Flicek, P.

Published
2009

23. Ensembl 2008

Author

Flicek, P., Aken, B. L., Beal, K., Ballester, B., Caccamo, M., Chen, Y., Clarke, L., Coates, G., Cunningham, F., Cutts, T., Down, T., Dyer, S. C., Eyre, T., Fitzgerald, S., Fernandez-Banet, J., Gräf, S., Haider, S., Hammond, M., Holland, R., Howe, K. L., Howe, K., Johnson, N., Jenkinson, A., Kähäri, A., Keefe, D., Kokocinski, F., Kulesha, E., Lawson, D., Longden, I., Megy, K., Meidl, P., Overduin, B., Parker, A., Pritchard, B., Prlic, A., Rice, S., Rios, D., Schuster, M., Sealy, I., Slater, G., Smedley, D., Spudich, G., Trevanion, S., Vilella, A. J., Vogel, J., White, S., Wood, M., Birney, E., Cox, T., Curwen, V., Durbin, R., Fernandez-Suarez, X. M., Herrero, J., Hubbard, T. J. P., Kasprzyk, A., Proctor, G., Smith, J., Ureta-Vidal, A., and Searle, S.

Published
2008

24. Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4through evolutionary conserved vertebrate gene analysis

Author

Owen, Nicholas, Toms, Maria, Young, Rodrigo M., Eintracht, Jonathan, Sarkar, Hajrah, Brooks, Brian P., Moosajee, Mariya, Ambrose, J.C., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de, Burca A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., Furió-Tarí, P., Hackett, J.M., Halai, D., Holman, J.E., Hubbard, T.J.P., Jackson, R., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., Maleady-Crowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Wood, S.M., and Zarowiecki, M.

Abstract

Ocular coloboma arises from genetic or environmental perturbations that inhibit optic fissure (OF) fusion during early eye development. Despite high genetic heterogeneity, 70% to 85% of patients remain molecularly undiagnosed. In this study, we have identified new potential causative genes using cross-species comparative meta-analysis.

Published
2022
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25. Germline selection shapes human mitochondrial DNA diversity

Author

Wei, W, Tuna, S, Keogh, MJ, Smith, KR, Aitman, TJ, Beales, PL, Bennett, DL, Gale, DP, Bitner-Glindzicz, MAK, Black, GC, Brennan, P, Elliott, P, Flinter, FA, Floto, RA, Houlden, H, Irving, M, Koziell, A, Maher, ER, Markus, HS, Morrell, NW, Newman, WG, Roberts, I, Sayer, JA, Smith, KGC, Taylor, JC, Watkins, H, Webster, AR, Wilkie, AOM, Williamson, C, Attwood, A, Brown, M, Brod, NC, Crisp-Hihn, A, Davis, J, Deevi, SVV, Dewhurst, EF, Edwards, K, Erwood, M, Fox, J, Frary, AJ, Hu, F, Jolley, J, Kingston, N, Linger, R, Mapeta, R, Martin, J, Meacham, S, Papadia, S, Rayner-Matthews, PJ, Samarghitean, C, Shamardina, O, Simeoni, I, Staines, S, Staples, E, Stark, H, Stephens, J, Titterton, C, Von Ziegenweidt, J, Watt, C, Whitehorn, D, Wood, Y, Yates, K, Yu, P, James, R, Ashford, S, Penkett, CJ, Stirrups, KE, Bariana, T, Lentaigne, C, Sivapalaratnam, S, Westbury, SK, Allsup, DJ, Bakchoul, T, Biss, T, Boyce, S, Collins, J, Collins, PW, Curry, NS, Downes, K, Dutt, T, Erber, WN, Evans, G, Everington, T, Favier, R, Gomez, K, Greene, D, Gresele, P, Hart, D, Kazmi, R, Kelly, AM, Lambert, M, Madan, B, Mangles, S, Mathias, M, Millar, C, Obaji, S, Peerlinck, K, Roughley, C, Schulman, S, Scully, M, Shapiro, SE, Sibson, K, Sims, MC, Tait, RC, Talks, K, Thys, C, Toh, C-H, Van Geet, C, Westwood, J-P, Mumford, AD, Ouwehand, WH, Freson, K, Laffan, MA, Tan, RYY, Harkness, K, Mehta, S, Muir, KW, Hassan, A, Traylor, M, Drazyk, AM, Parry, D, Ahmed, M, Kazkaz, H, Vandersteen, AM, Ormondroyd, E, Thomson, K, Dent, T, Buchan, RJ, Bueser, T, Carr-White, G, Cook, S, Daniels, MJ, Harper, AR, Ware, JS, Dixon, PH, Chambers, J, Cheng, F, Estiu, MC, Hague, WM, Marschall, H-U, Vazquez-Lopez, M, Arno, G, French, CE, Michaelides, M, Moore, AT, Sanchis-Juan, A, Carss, K, Raymond, FL, Chinnery, PF, Griffiths, P, Horvath, R, Hudson, G, Jurkute, N, Pyle, A, Yu-Wai-Man, P, Whitworth, J, Adlard, J, Armstrong, R, Brewer, C, Casey, R, Cole, TRP, Evans, DG, Greenhalgh, L, Hanson, HL, Hoffman, J, Izatt, L, Kumar, A, Lalloo, F, Ong, KR, Park, S-M, Searle, C, Side, L, Snape, K, Woodward, E, Tischkowitz, M, Grozeva, D, Kurian, MA, Themistocleous, AC, Gosal, D, Marshall, A, Matthews, E, McCarthy, MI, Renton, T, Rice, ASC, Vale, T, Walker, SM, Woods, CG, Thaventhiran, JE, Allen, HL, Savic, S, Alachkar, H, Antrobus, R, Baxendale, HE, Browning, MJ, Buckland, MS, Cooper, N, Edgar, JDM, Egner, W, Gilmour, KC, Goddard, S, Gordins, P, Grigoriadou, S, Hackett, S, Hague, R, Hayman, G, Herwadkar, A, Huissoon, AP, Jolles, S, Kelleher, P, Kumararatne, D, Longhurst, H, Lorenzo, LE, Lyons, PA, Maimaris, J, Noorani, S, Richter, A, Sargur, RB, Sewell, WAC, Thomas, D, Thomas, MJ, Worth, A, Yong, PFK, Kuijpers, TW, Thrasher, AJ, Levine, AP, Sadeghi-Alavijeh, O, Wong, EKS, Cook, HT, Chan, MMY, Hall, M, Harris, C, McAlinden, P, Marchbank, KJ, Marks, S, Maxwell, H, Mozere, M, Wessels, J, Johnson, SA, Bleda, M, Hadinnapola, C, Haimel, M, Swietlik, E, Bogaard, H, Church, C, Coghlan, G, Condliffe, R, Corris, P, Danesino, C, Eyries, M, Gall, H, Ghofrani, H-A, Gibbs, JSR, Girerd, B, Holden, S, Houweling, A, Howard, LS, Humbert, M, Kiely, DG, Kovacs, G, Lawrie, A, Ross, RVM, Moledina, S, Montani, D, Newnham, M, Olschewski, A, Olschewski, H, Peacock, A, Pepke-Zaba, J, Scelsi, L, Seeger, W, Soubrier, F, Suntharalingam, J, Toshner, M, Treacy, C, Trembath, R, Noordegraaf, AV, Waisfisz, Q, Wharton, J, Wilkins, MR, Wort, SJ, Graf, S, Louka, E, Roy, NB, Rao, A, Ancliff, P, Babbs, C, Layton, DM, Mead, AJ, O'Sullivan, J, Okoli, S, Saleem, M, Bierzynska, A, Diz, CB, Colby, E, Ekani, MN, Satchell, S, Fowler, T, Rendon, A, Scott, R, Smedley, D, Thomas, E, Caulfield, M, Abbs, S, Burrows, N, Chitre, M, Gattens, M, Gurnell, M, Kelsall, W, Poole, KES, Ross-Russell, R, Spasic-Boskovic, O, Twiss, P, Wagner, A, Banka, S, Clayton-Smith, J, Douzgou, S, Abulhoul, L, Aurora, P, Bockenhauer, D, Cleary, M, Dattani, M, Ganesan, V, Pilkington, C, Rahman, S, Shah, N, Wedderburn, L, Compton, CJ, Deshpande, C, Fassihi, H, Haque, E, Josifova, D, Mohammed, SN, Robert, L, Rose, SJ, Ruddy, DM, Sarkany, RN, Sayer, G, Shaw, AC, Campbell, C, Gibson, K, Koelling, N, Lester, T, Nemeth, AH, Palles, C, Patel, S, Sen, A, Taylor, J, Tomlinson, IP, Malka, S, Browning, AC, Burn, J, De Soyza, A, Graham, J, Pearce, S, Quinton, R, Schaefer, AM, Wilson, BT, Wright, M, Simpson, M, Syrris, P, Bradley, JR, Turro, E, ARD - Amsterdam Reproduction and Development, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Medical Research Council (MRC), Wellcome Trust, Wei, Wei [0000-0002-2945-3543], Tuna, Salih [0000-0003-3606-4367], Smith, Katherine R [0000-0002-0329-5938], Beales, Phil L [0000-0002-9164-9782], Bennett, David L [0000-0002-7996-2696], Gale, Daniel P [0000-0002-9170-1579], Brennan, Paul [0000-0003-1128-6254], Elliott, Perry [0000-0003-3383-3984], Floto, R Andres [0000-0002-2188-5659], Houlden, Henry [0000-0002-2866-7777], Koziell, Ania [0000-0003-4882-0246], Maher, Eamonn R [0000-0002-6226-6918], Markus, Hugh S [0000-0002-9794-5996], Morrell, Nicholas W [0000-0001-5700-9792], Newman, William G [0000-0002-6382-4678], Sayer, John A [0000-0003-1881-3782], Smith, Kenneth GC [0000-0003-3829-4326], Taylor, Jenny C [0000-0003-3602-5704], Watkins, Hugh [0000-0002-5287-9016], Webster, Andrew R [0000-0001-6915-9560], Wilkie, Andrew OM [0000-0002-2972-5481], Penkett, Christopher J [0000-0003-4006-7261], Stirrups, Kathleen E [0000-0002-6823-3252], Rendon, Augusto [0000-0001-8994-0039], Bradley, John R [0000-0002-7774-8805], Turro, Ernest [0000-0002-1820-6563], Chinnery, Patrick F [0000-0002-7065-6617], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Non-Mendelian inheritance, Genome, Mitochondrial/genetics, DNA, Mitochondrial/genetics, 0302 clinical medicine, Ovum/growth & development, MTDNA, TRANSCRIPTION, Genetics, education.field_of_study, Multidisciplinary, NIHR BioResource–Rare Diseases, ASSOCIATION, Heteroplasmy, Mitochondrial, Multidisciplinary Sciences, GENOME, REPLACEMENT, Science & Technology - Other Topics, Female, Maternal Inheritance, Mitochondrial DNA, General Science & Technology, Genetic genealogy, Population, Biology, Human mitochondrial genetics, SEQUENCE, DNA, Mitochondrial, 03 medical and health sciences, Genetic, 100,000 Genomes Project–Rare Diseases Pilot, Genetic variation, MD Multidisciplinary, Humans, Selection, Genetic, education, Selection, Ovum, Science & Technology, MUTATIONS, Genetic Variation, DNA, LEIGH-DISEASE, 030104 developmental biology, REPLICATION, Genome, Mitochondrial, HETEROPLASMY, 030217 neurology & neurosurgery
Abstract

INTRODUCTION Only 2.4% of the 16.5-kb mitochondrial DNA (mtDNA) genome shows homoplasmic variation at >1% frequency in humans. Migration patterns have contributed to geographic differences in the frequency of common genetic variants, but population genetic evidence indicates that selection shapes the evolving mtDNA phylogeny. The mechanism and timing of this process are not clear. Unlike the nuclear genome, mtDNA is maternally transmitted and there are many copies in each cell. Initially, a new genetic variant affects only a proportion of the mtDNA (heteroplasmy). During female germ cell development, a reduction in the amount of mtDNA per cell causes a “genetic bottleneck,” which leads to rapid segregation of mtDNA molecules and different levels of heteroplasmy between siblings. Although heteroplasmy is primarily governed by random genetic drift, there is evidence of selection occurring during this process in animals. Yet it has been difficult to demonstrate this convincingly in humans. RATIONALE To determine whether there is selection for or against heteroplasmic mtDNA variants during transmission, we studied 12,975 whole-genome sequences, including 1526 mother–offspring pairs of which 45.1% had heteroplasmy affecting >1% of mtDNA molecules. Harnessing both the mtDNA and nuclear genome sequences, we then determined whether the nuclear genetic background influenced mtDNA heteroplasmy, validating our findings in another 40,325 individuals. RESULTS Previously unknown mtDNA variants were less likely to be inherited than known variants, in which the level of heteroplasmy tended to increase on transmission. Variants in the ribosomal RNA genes were less likely to be transmitted, whereas variants in the noncoding displacement (D)–loop were more likely to be transmitted. MtDNA variants predicted to affect the protein sequence tended to have lower heteroplasmy levels than synonymous variants. In 12,975 individuals, we identified a correlation between the location of heteroplasmic sites and known D-loop polymorphisms, including the absence of variants in critical sites required for mtDNA transcription and replication. We defined 206 unrelated individuals for which the nuclear and mitochondrial genomes were from different human populations. In these individuals, new population-specific heteroplasmies were more likely to match the nuclear genetic ancestry than the mitochondrial genome on which the mutations occurred. These findings were independently replicated in 654 additional unrelated individuals. CONCLUSION The characteristics of mtDNA in the human population are shaped by selective forces acting on heteroplasmy within the female germ line and are influenced by the nuclear genetic background. The signature of selection can be seen over one generation, ensuring consistency between these two independent genetic systems.

Published
2019
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26. Analysis of mammalian gene function through mouse phenotyping

Author

Smedley D. and IMPC (KOMP/IPAD-MD Data WGroup)

Subjects
disease model, mouse mutant
Abstract

Over the last decade, new sequencing technologies have enabled the discovery of numerous new disease-associated genes. However, for many genes we still know very little about their function and potential role in disease and many patients remain undiagnosed. Model organisms facilitate the exploration of genotype to phenotype associations and public databases of this knowledge allow us to assess genes with no previous involvement in human disease. Towards this goal, the International Mouse Phenotyping Consortium (IMPC) is building the first complete functional catalogue of the mammalian genome by producing and phenotyping a knockout mouse strain for every protein coding gene.

Published
2019

27. Ensembl 2007

Author

Hubbard, T. J. P., Aken, B. L., Beal, K., Ballester, B., Caccamo, M., Chen, Y., Clarke, L., Coates, G., Cunningham, F., Cutts, T., Down, T., Dyer, S. C., Fitzgerald, S., Fernandez-Banet, J., Graf, S., Haider, S., Hammond, M., Herrero, J., Holland, R., Howe, K., Johnson, N., Kahari, A., Keefe, D., Kokocinski, F., Kulesha, E., Lawson, D., Longden, I., Melsopp, C., Megy, K., Meidl, P., Ouverdin, B., Parker, A., Prlic, A., Rice, S., Rios, D., Schuster, M., Sealy, I., Severin, J., Slater, G., Smedley, D., Spudich, G., Trevanion, S., Vilella, A., Vogel, J., White, S., Wood, M., Cox, T., Curwen, V., Durbin, R., Fernandez-Suarez, X. M., Flicek, P., Kasprzyk, A., Proctor, G., Searle, S., Smith, J., Ureta-Vidal, A., and Birney, E.

Published
2007

28. Ensembl 2006

Author

Birney, E., Andrews, D., Caccamo, M., Chen, Y., Clarke, L., Coates, G., Cox, T., Cunningham, F., Curwen, V., Cutts, T., Down, T., Durbin, R., Fernandez-Suarez, X. M., Flicek, P., Gräf, S., Hammond, M., Herrero, J., Howe, K., Iyer, V., Jekosch, K., Kähäri, A., Kasprzyk, A., Keefe, D., Kokocinski, F., Kulesha, E., London, D., Longden, I., Melsopp, C., Meidl, P., Overduin, B., Parker, A., Proctor, G., Prlic, A., Rae, M., Rios, D., Redmond, S., Schuster, M., Sealy, I., Searle, S., Severin, J., Slater, G., Smedley, D., Smith, J., Stabenau, A., Stalker, J., Trevanion, S., Ureta-Vidal, A., Vogel, J., White, S., Woodwark, C., and Hubbard, T. J. P.

Published
2006

29. Ensembl 2005

Author

Hubbard, T., Andrews, D., Caccamo, M., Cameron, G., Chen, Y., Clamp, M., Clarke, L., Coates, G., Cox, T., Cunningham, F., Curwen, V., Cutts, T., Down, T., Durbin, R., Fernandez-Suarez, X. M., Gilbert, J., Hammond, M., Herrero, J., Hotz, H., Howe, K., Iyer, V., Jekosch, K., Kahari, A., Kasprzyk, A., Keefe, D., Keenan, S., Kokocinsci, F., London, D., Longden, I., McVicker, G., Melsopp, C., Meidl, P., Potter, S., Proctor, G., Rae, M., Rios, D., Schuster, M., Searle, S., Severin, J., Slater, G., Smedley, D., Smith, J., Spooner, W., Stabenau, A., Stalker, J., Storey, R., Trevanion, S., Ureta-Vidal, A., Vogel, J., White, S., Woodwark, C., and Birney, E.

Published
2005

30. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Author

Köhler, S., Carmody, L., Vasilevsky, N., Jacobsen, J.O.B., Danis, D., Gourdine, J.P., Gargano, M., Harris, N.L., Matentzoglu, N., McMurry, J.A., Osumi-Sutherland, D., Cipriani, V., Balhoff, J.P., Conlin, T., Blau, H., Baynam, G., Palmer, Richard, Gratian, D., Dawkins, H., Segal, M., Jansen, A.C., Muaz, A., Chang, W.H., Bergerson, J., Laulederkind, S.J.F., Yüksel, Z., Beltran, S., Freeman, A.F., Sergouniotis, P.I., Durkin, D., Storm, A.L., Hanauer, M., Brudno, M., Bello, S.M., Sincan, M., Rageth, K., Wheeler, M.T., Oegema, R., Lourghi, H., Della Rocca, M.G., Thompson, R., Castellanos, F., Priest, J., Cunningham-Rundles, C., Hegde, A., Lovering, R.C., Hajek, C., Olry, A., Notarangelo, L., Similuk, M., Zhang, X.A., Gómez-Andrés, D., Lochmüller, H., Dollfus, H., Rosenzweig, S., Marwaha, S., Rath, A., Sullivan, K., Smith, C., Milner, J.D., Leroux, D., Boerkoel, C.F., Klion, A., Carter, M.C., Groza, T., Smedley, D., Haendel, M.A., Mungall, C., Robinson, P.N., Köhler, S., Carmody, L., Vasilevsky, N., Jacobsen, J.O.B., Danis, D., Gourdine, J.P., Gargano, M., Harris, N.L., Matentzoglu, N., McMurry, J.A., Osumi-Sutherland, D., Cipriani, V., Balhoff, J.P., Conlin, T., Blau, H., Baynam, G., Palmer, Richard, Gratian, D., Dawkins, H., Segal, M., Jansen, A.C., Muaz, A., Chang, W.H., Bergerson, J., Laulederkind, S.J.F., Yüksel, Z., Beltran, S., Freeman, A.F., Sergouniotis, P.I., Durkin, D., Storm, A.L., Hanauer, M., Brudno, M., Bello, S.M., Sincan, M., Rageth, K., Wheeler, M.T., Oegema, R., Lourghi, H., Della Rocca, M.G., Thompson, R., Castellanos, F., Priest, J., Cunningham-Rundles, C., Hegde, A., Lovering, R.C., Hajek, C., Olry, A., Notarangelo, L., Similuk, M., Zhang, X.A., Gómez-Andrés, D., Lochmüller, H., Dollfus, H., Rosenzweig, S., Marwaha, S., Rath, A., Sullivan, K., Smith, C., Milner, J.D., Leroux, D., Boerkoel, C.F., Klion, A., Carter, M.C., Groza, T., Smedley, D., Haendel, M.A., Mungall, C., and Robinson, P.N.

Abstract

The Human Phenotype Ontology (HPO) - a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases - is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

Published
2019

31. Ensembl 2004

Author

Birney, E., Andrews, D., Bevan, P., Caccamo, M., Cameron, G., Chen, Y., Clarke, L., Coates, G., Cox, T., Cuff, J., Curwen, V., Cutts, T., Down, T., Durbin, R., Eyras, E., Fernandez-Suarez, X. M., Gane, P., Gibbins, B., Gilbert, J., Hammond, M., Hotz, H., Iyer, V., Kahari, A., Jekosch, K., Kasprzyk, A., Keefe, D., Keenan, S., Lehvaslaiho, H., McVicker, G., Melsopp, C., Meidl, P., Mongin, E., Pettett, R., Potter, S., Proctor, G., Rae, M., Searle, S., Slater, G., Smedley, D., Smith, J., Spooner, W., Stabenau, A., Stalker, J., Storey, R., Ureta-Vidal, A., Woodwark, C., Clamp, M., and Hubbard, T.

Published
2004

34. INFRAFRONTIER-providing mutant mouse resources as research tools for the international scientific community

Author

Meehan, TF, Chen, CK, Koscielny, G, Relac, M, Wilkinson, P, Flicek, P, Parkinson, H, Castro, A, Fessele, S, Steinkamp, R, Hagn, M, Raess, M, de Angelis, MH, Bottomley, J, Ramirez-Solis, R, Smedley, D, Ball, S, Blake, A, Fray, M, Kenyon, J, Mallon, AM, Brown, S, Massimi, M, Matteoni, R, Tocchini-Valentini, G, Herault, Y, Kollias, G, Ulfhake, B, Demengeot, J, Fremond, C, Bosch, F, Montoliu, L, Soininen, R, Schughart, K, Brakebusch, C, Sedlacek, R, Rulicke, T, McKerlie, C, Malissen, B, Iraqi, F, Jonkers, J, Russig, H, Huylebroeck, Danny, Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany., and Cell biology

Subjects
Internet, business.industry, Knowledge Bases, Mutant, Biology, Mice, Mutant Strains, Biotechnology, World Wide Web, Phenotype, SDG 3 - Good Health and Well-being, Databases, Genetic, Models, Animal, Genetics, Database Issue, Animals, The Internet, business, Embryonic Stem Cells
Abstract

This deposit is composed by a publication in which the IGC' authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and could only be accessed by two ways: either by requesting a legal copy to the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383977/ The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI).

Published
2015

35. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources

Author

Köhler, S., Carmody, L., Vasilevsky, N., Jacobsen, J.O.B, Danis, D., Gourdine, J-P, Gargano, M., Harris, N.L, Matentzoglu, N., McMurry, J.A., Osumi-Sutherland, D., Cipriani, V., Balhoff, J.P., Conlin, T., Blau, H., Baynam, G., Palmer, R., Gratian, D., Dawkins, H., Segal, M., Jansen, A.C., Muaz, A., Chang, W.H., Bergerson, J., Laulederkind, S.J.F., Yüksel, Z., Beltran, S., Freeman, A.F., Sergouniotis, P.I., Durkin, D., Storm, A.L., Hanauer, M., Brudno, M., Bello, S.M., Sincan, M., Rageth, K., Wheeler, M.T., Oegema, R., Lourghi, H., Della Rocca, M.G., Thompson, R., Castellanos, F., Priest, J., Cunningham-Rundles, C., Hegde, A., Lovering, R.C., Hajek, C., Olry, A., Notarangelo, L., Similuk, M., Zhang, X.A., Gómez-Andrés, D., Lochmüller, H., Dollfus, H., Rosenzweig, S., Marwaha, S., Rath, A., Sullivan, K., Smith, C., Milner, J.D., Leroux, D., Boerkoel, C.F., Klion, A., Carter, M.C., Groza, T., Smedley, D., Haendel, M.A, Mungall, C., Robinson, P.N., Köhler, S., Carmody, L., Vasilevsky, N., Jacobsen, J.O.B, Danis, D., Gourdine, J-P, Gargano, M., Harris, N.L, Matentzoglu, N., McMurry, J.A., Osumi-Sutherland, D., Cipriani, V., Balhoff, J.P., Conlin, T., Blau, H., Baynam, G., Palmer, R., Gratian, D., Dawkins, H., Segal, M., Jansen, A.C., Muaz, A., Chang, W.H., Bergerson, J., Laulederkind, S.J.F., Yüksel, Z., Beltran, S., Freeman, A.F., Sergouniotis, P.I., Durkin, D., Storm, A.L., Hanauer, M., Brudno, M., Bello, S.M., Sincan, M., Rageth, K., Wheeler, M.T., Oegema, R., Lourghi, H., Della Rocca, M.G., Thompson, R., Castellanos, F., Priest, J., Cunningham-Rundles, C., Hegde, A., Lovering, R.C., Hajek, C., Olry, A., Notarangelo, L., Similuk, M., Zhang, X.A., Gómez-Andrés, D., Lochmüller, H., Dollfus, H., Rosenzweig, S., Marwaha, S., Rath, A., Sullivan, K., Smith, C., Milner, J.D., Leroux, D., Boerkoel, C.F., Klion, A., Carter, M.C., Groza, T., Smedley, D., Haendel, M.A, Mungall, C., and Robinson, P.N.

Abstract

The Human Phenotype Ontology (HPO)—a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases—is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO’s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes.

Published
2018

36. Biallelic CRELD1variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections

Author

Jeffries, Lauren, Mis, Emily K., McWalter, Kirsty, Donkervoort, Sandra, Brodsky, Nina N., Carpier, Jean-Marie, Ji, Weizhen, Ionita, Cristian, Roy, Bhaskar, Morrow, Jon S., Darbinyan, Armine, Iyer, Krishna, Aul, Ritu B., Banka, Siddharth, Chao, Katherine R., Cobbold, Laura, Cohen, Stacey, Custodio, Helena M., Drummond-Borg, Margaret, Elmslie, Frances, Finanger, Erika, Hainline, Bryan E., Helbig, Ingo, Hewson, Stacy, Hu, Ying, Jackson, Adam, Josifova, Dragana, Konstantino, Monica, Leach, Meganne E., Mak, Bryan, McCormick, David, McGee, Elisabeth, Nelson, Stanley, Nguyen, Joanne, Nugent, Kimberly, Ortega, Lucy, Goodkin, Howard P., Roeder, Elizabeth, Roy, Sani, Sapp, Katie, Saade, Dimah, Sisodiya, Sanjay M., Stals, Karen, Towner, Shelley, Wilson, William, Borras, Silvia, Clark, Caroline, Dean, John, Miedzybrodzka, Zosia, Ross, Alison, Tennant, Stephen, Dabir, Tabib, Donnelly, Deirdre, Humphreys, Mervyn, Magee, Alex, McConnell, Vivienne, McKee, Shane, McNerlan, Susan, Morrison, Patrick J., Rea, Gillian, Stewart, Fiona, Cole, Trevor, Cooper, Nicola, Cooper-Charles, Lisa, Cox, Helen, Islam, Lily, Jarvis, Joanna, Keelagher, Rebecca, Lim, Derek, McMullan, Dominic, Morton, Jenny, Naik, Swati, O’Driscoll, Mary, Ong, Kai-Ren, Osio, Deborah, Ragge, Nicola, Turton, Sarah, Vogt, Julie, Williams, Denise, Bodek, Simon, Donaldson, Alan, Hills, Alison, Low, Karen, Newbury-Ecob, Ruth, Norman, Andrew M., Roberts, Eileen, Scurr, Ingrid, Smithson, Sarah, Tooley, Madeleine, Abbs, Steve, Armstrong, Ruth, Dunn, Carolyn, Holden, Simon, Park, Soo-Mi, Paterson, Joan, Raymond, Lucy, Reid, Evan, Sandford, Richard, Simonic, Ingrid, Tischkowitz, Marc, Woods, Geoff, Bradley, Lisa, Comerford, Joanne, Green, Andrew, Lynch, Sally, McQuaid, Shirley, Mullaney, Brendan, Berg, Jonathan, Goudie, David, Mavrak, Eleni, McLean, Joanne, McWilliam, Catherine, Reavey, Eleanor, Azam, Tara, Cleary, Elaine, Jackson, Andrew, Lam, Wayne, Lampe, Anne, Moore, David, Porteous, Mary, Baple, Emma, Baptista, Júlia, Brewer, Carole, Castle, Bruce, Kivuva, Emma, Owens, Martina, Rankin, Julia, Shaw-Smith, Charles, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Bradley, Therese, Davidson, Rosemarie, Gardiner, Carol, Joss, Shelagh, Kinning, Esther, Longman, Cheryl, McGowan, Ruth, Murday, Victoria, Pilz, Daniela, Tobias, Edward, Whiteford, Margo, Williams, Nicola, Barnicoat, Angela, Clement, Emma, Faravelli, Francesca, Hurst, Jane, Jenkins, Lucy, Jones, Wendy, Ajith Kumar, V.K., Lees, Melissa, Loughlin, Sam, Male, Alison, Morrogh, Deborah, Rosser, Elisabeth, Scott, Richard, Wilson, Louise, Beleza, Ana, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Irving, Melita, Izatt, Louise, Josifova, Dragana, Mohammed, Shehla, Molenda, Aneta, Robert, Leema, Roworth, Wendy, Ruddy, Deborah, Ryten, Mina, Yau, Shu, Bennett, Christopher, Blyth, Moira, Campbell, Jennifer, Coates, Andrea, Dobbie, Angus, Hewitt, Sarah, Hobson, Emma, Jackson, Eilidh, Jewell, Rosalyn, Kraus, Alison, Prescott, Katrina, Sheridan, Eamonn, Thomson, Jenny, Bradshaw, Kirsty, Dixit, Abhijit, Eason, Jacqueline, Haines, Rebecca, Harrison, Rachel, Mutch, Stacey, Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Sharif, Abid, Suri, Mohnish, Vasudevan, Pradeep, Canham, Natalie, Ellis, Ian, Greenhalgh, Lynn, Howard, Emma, Stinton, Victoria, Swale, Andrew, Weber, Astrid, Banka, Siddharth, Breen, Catherine, Briggs, Tracy, Burkitt-Wright, Emma, Chandler, Kate, Clayton-Smith, Jill, Donnai, Dian, Douzgou, Sofia, Gaunt, Lorraine, Jones, Elizabeth, Kerr, Bronwyn, Langley, Claire, Metcalfe, Kay, Smith, Audrey, Wright, Ronnie, Bourn, David, Burn, John, Fisher, Richard, Hellens, Steve, Henderson, Alex, Montgomery, Tara, Splitt, Miranda, Straub, Volker, Wright, Michael, Zwolinski, Simon, Allen, Zoe, Bernhard, Birgitta, Brady, Angela, Brooks, Claire, Busby, Louise, Clowes, Virginia, Ghali, Neeti, Holder, Susan, Ibitoye, Rita, Wakeling, Emma, Blair, Edward, Carmichael, Jenny, Cilliers, Deirdre, Clasper, Susan, Gibbons, Richard, Kini, Usha, Lester, Tracy, Nemeth, Andrea, Poulton, Joanna, Price, Sue, Shears, Debbie, Stewart, Helen, Wilkie, Andrew, Albaba, Shadi, Baker, Duncan, Balasubramanian, Meena, Johnson, Diana, Parker, Michael, Quarrell, Oliver, Stewart, Alison, Willoughby, Josh, Crosby, Charlene, Elmslie, Frances, Homfray, Tessa, Jin, Huilin, Lahiri, Nayana, Mansour, Sahar, Marks, Karen, McEntagart, Meriel, Saggar, Anand, Tatton-Brown, Kate, Butler, Rachel, Clarke, Angus, Corrin, Sian, Fry, Andrew, Kamath, Arveen, McCann, Emma, Mugalaasi, Hood, Pottinger, Caroline, Procter, Annie, Sampson, Julian, Sansbury, Francis, Varghese, Vinod, Baralle, Diana, Callaway, Alison, Cassidy, Emma J., Daniels, Stacey, Douglas, Andrew, Foulds, Nicola, Hunt, David, Kharbanda, Mira, Lachlan, Katherine, Mercer, Catherine, Side, Lucy, Temple, I. Karen, Wellesley, Diana, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., FurióTarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., MaleadyCrowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Acosta, Maria T., Adam, Margaret, Adams, David R., Agrawal, Pankaj B., Alejandro, Mercedes E., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dhar, Shweta U., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Douine, Emilie D., Draper, David D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Falk, Marni, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Findley, Laurie C., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Glass, Ian, Godfrey, Rena A., Golden-Grant, Katie, Goldman, Alica M., Goldstein, David B., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Gutierrez, Irma, Hahn, Sihoun, Hamid, Rizwan, Hanchard, Neil A., Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Johnston, Jean M., Karaviti, Lefkothea, Kelley, Emily G., Kennedy, Jennifer, Kiley, Dana, Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Krier, Joel B., Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Mak, Bryan, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McCormack, Colleen E., McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nakano-Okuno, Mariko, Nath, Avi, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Papp, Jeanette C., Parker, Neil H., Phillips, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Scott, C. Ron, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Sharma, Prashant, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Solnica-Krezel, Lilianna, Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tamburro, Cecelia P., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Wallace, Stephanie, Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-Kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Woods, Jeremy D., Yamamoto, Shinya, Yang, John, Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Khokha, Mustafa K., Bönnemann, Carsten G., Lucas, Carrie L., and Lakhani, Saquib A.

Abstract

We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor–like domains 1 (CRELD1) gene variants.

Published
2024
Full Text
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37. The Human Phenotype Ontology in 2017

Author

Kohler, S., Vasilevsky, N.A., Engelstad, M., Foster, E., McMurry, J., Ayme, S., Baynam, G., Bello, S.M., Boerkoel, C.F., Boycott, K.M., Brudno, M., Buske, O.J., Chinnery, P.F., Cipriani, V., Connell, L.E., Dawkins, H.J., DeMare, L.E., Devereau, A.D., Vries, B.B. de, Firth, H.V., Freson, K., Greene, D., Hamosh, A., Helbig, I., Hum, C., Jahn, J.A., James, R., Krause, R., Laulederkind, S.J.F., Lochmuller, H., Lyon, G.J., Ogishima, S., Olry, A., Ouwehand, W.H., Pontikos, N., Rath, A., Schaefer, F., Scott, R.H., Segal, M., Sergouniotis, P.I., Sever, R., Smith, C.L., Straub, V., Thompson, R., Turner, C., Turro, E., Veltman, M.W., Vulliamy, T., Yu, J., Ziegenweidt, J. von, Zankl, A., Zuchner, S., Zemojtel, T., Jacobsen, J.O., Groza, T., Smedley, D., Mungall, C.J., Haendel, M., Robinson, P.N., Kohler, S., Vasilevsky, N.A., Engelstad, M., Foster, E., McMurry, J., Ayme, S., Baynam, G., Bello, S.M., Boerkoel, C.F., Boycott, K.M., Brudno, M., Buske, O.J., Chinnery, P.F., Cipriani, V., Connell, L.E., Dawkins, H.J., DeMare, L.E., Devereau, A.D., Vries, B.B. de, Firth, H.V., Freson, K., Greene, D., Hamosh, A., Helbig, I., Hum, C., Jahn, J.A., James, R., Krause, R., Laulederkind, S.J.F., Lochmuller, H., Lyon, G.J., Ogishima, S., Olry, A., Ouwehand, W.H., Pontikos, N., Rath, A., Schaefer, F., Scott, R.H., Segal, M., Sergouniotis, P.I., Sever, R., Smith, C.L., Straub, V., Thompson, R., Turner, C., Turro, E., Veltman, M.W., Vulliamy, T., Yu, J., Ziegenweidt, J. von, Zankl, A., Zuchner, S., Zemojtel, T., Jacobsen, J.O., Groza, T., Smedley, D., Mungall, C.J., Haendel, M., and Robinson, P.N.

Abstract

Contains fulltext : 169849.pdf (publisher's version ) (Open Access), Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Published
2017

38. The human phenotype ontology in 2017

Author

Köhler, S, Vasilevsky, NA, Engelstad, M, Foster, E, McMurry, J, Aymé, S, Baynam, G, Bello, SM, Boerkoel, CF, Boycott, KM, Brudno, M, Buske, OJ, Chinnery, PF, Cipriani, V, Connell, LE, Dawkins, HJS, DeMare, LE, Devereau, AD, De Vries, BBA, Firth, HV, Freson, K, Greene, D, Hamosh, A, Helbig, I, Hum, C, Jähn, JA, James, R, Krause, R, Laulederkind, SJF, Lochmüller, H, Lyon, GJ, Ogishima, S, Olry, A, Ouwehand, WH, Pontikos, N, Rath, A, Schaefer, F, Scott, RH, Segal, M, Sergouniotis, PI, Sever, R, Smith, CL, Straub, V, Thompson, R, Turner, C, Turro, E, Veltman, MWM, Vulliamy, T, Yu, J, Von Ziegenweidt, J, Zankl, A, Züchner, S, Zemojtel, T, Jacobsen, JOB, Groza, T, Smedley, D, Mungall, CJ, Haendel, M, Robinson, PN, Köhler, S, Vasilevsky, NA, Engelstad, M, Foster, E, McMurry, J, Aymé, S, Baynam, G, Bello, SM, Boerkoel, CF, Boycott, KM, Brudno, M, Buske, OJ, Chinnery, PF, Cipriani, V, Connell, LE, Dawkins, HJS, DeMare, LE, Devereau, AD, De Vries, BBA, Firth, HV, Freson, K, Greene, D, Hamosh, A, Helbig, I, Hum, C, Jähn, JA, James, R, Krause, R, Laulederkind, SJF, Lochmüller, H, Lyon, GJ, Ogishima, S, Olry, A, Ouwehand, WH, Pontikos, N, Rath, A, Schaefer, F, Scott, RH, Segal, M, Sergouniotis, PI, Sever, R, Smith, CL, Straub, V, Thompson, R, Turner, C, Turro, E, Veltman, MWM, Vulliamy, T, Yu, J, Von Ziegenweidt, J, Zankl, A, Züchner, S, Zemojtel, T, Jacobsen, JOB, Groza, T, Smedley, D, Mungall, CJ, Haendel, M, and Robinson, PN

Abstract

© The Author(s) 2016. Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Published
2017

39. The Monarch Initiative: An integrative data and analytic platform connecting phenotypes to genotypes across species

Author

Mungall, CJ, McMurry, JA, Kohler, S, Balhoff, JP, Borromeo, C, Brush, M, Carbon, S, Conlin, T, Dunn, N, Engelstad, M, Foster, E, Gourdine, JP, Jacobsen, JOB, Keith, D, Laraway, B, Lewis, SE, Xuan, JN, Shefchek, K, Vasilevsky, N, Yuan, Z, Washington, N, Hochheiser, H, Groza, T, Smedley, D, Robinson, PN, Haendel, MA, Mungall, CJ, McMurry, JA, Kohler, S, Balhoff, JP, Borromeo, C, Brush, M, Carbon, S, Conlin, T, Dunn, N, Engelstad, M, Foster, E, Gourdine, JP, Jacobsen, JOB, Keith, D, Laraway, B, Lewis, SE, Xuan, JN, Shefchek, K, Vasilevsky, N, Yuan, Z, Washington, N, Hochheiser, H, Groza, T, Smedley, D, Robinson, PN, and Haendel, MA

Abstract

© The Author(s). The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Nonhuman organisms have proven instrumental in revealing biological mechanisms. Advanced informatics tools can identify phenotypically relevant disease models in research and diagnostic contexts. Large-scale integration of model organism and clinical research data can provide a breadth of knowledge not available from individual sources and can provide contextualization of data back to these sources. The Monarch Initiative (monarchinitiative.org) is a collaborative, open science effort that aims to semantically integrate genotype-phenotype data from many species and sources in order to support precision medicine, disease modeling, and mechanistic exploration. Our integrated knowledge graph, analytic tools, and web services enable diverse users to explore relationships between phenotypes and genotypes across species.

Published
2017

42. Ensembl 2008

Author

Flicek, P., Aken, B., Beal, K., Ballester, Benoit, Caccamo, M., Chen, Y., Clarke, L., Coates, G., Cunningham, F., Cutts, T., Down, T., Dyer, S., Eyre, T., Fitzgerald, S., Fernandez-Banet, J., Gräf, S., Haider, S., Hammond, M., Holland, R., Howe, K., Johnson, N., Jenkinson, A., Kähäri, A., Keefe, D., Kokocinski, F., Kulesha, E., Lawson, D., Longden, I., Megy, K., Meidl, P., Overduin, B., Parker, A., Pritchard, B., Prlic, A., Rice, S., Rios, D., Schuster, M., Sealy, I., Slater, G., Smedley, D., Spudich, G., Trevanion, S., Vilella, A., Vogel, J., White, S., Wood, M., Birney, E., Cox, T., Curwen, V., Durbin, R., Fernandez-Suarez, X. M., Herrero, J., Hubbard, J., Kasprzyk, A., Proctor, G., Smith, J., Ureta-Vidal, A., Searle, S., Graf, S., Kahari, A., Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Expert and Training Centre for Breast Cancer Screening, Radboud University Medical Center [Nijmegen], Techniques de l'Informatique et de la Microélectronique pour l'Architecture des systèmes intégrés (TIMA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Institut de physique du globe de Strasbourg (IPGS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Dep. of Energy, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Techniques of Informatics and Microelectronics for integrated systems Architecture (TIMA), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
Internet, 0303 health sciences, 030302 biochemistry & molecular biology, Articles, Genomics, Mice, User-Computer Interface, 03 medical and health sciences, ComputingMethodologies_PATTERNRECOGNITION, Databases, Genetic, Computer Graphics, Genetics, Animals, Humans, Regulatory Elements, Transcriptional, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Software, 030304 developmental biology
Abstract

International audience; The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein–DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Published
2007

43. A gene expression resource generated by genome-wide lacZ profiling in the mouse

Author

Tuck E, Estabel J, Oellrich A, Ak, Maguire, Ha, Adissu, Souter L, Siragher E, Lillistone C, Al, Green, Hw, Jones, Dm, Carragher, Natasha Karp, Smedley D, Nc, Adams, Sanger Institute Mouse Genetics Project, Jn, Bussell, Dj, Adams, Ramírez-Solis R, Kp, Steel, Galli A, and Jk, White

Subjects
Resource, Mouse, Neuroscience (miscellaneous), lcsh:Medicine, Gene Expression, Medicine (miscellaneous), Genome-wide association study, Computational biology, Biology, Genome, General Biochemistry, Genetics and Molecular Biology, Mice, Immunology and Microbiology (miscellaneous), Genes, Reporter, Gene expression, lcsh:Pathology, Animals, Humans, Resource Article, Gene, Genetics, Gene Expression Profiling, lcsh:R, Phenotype, Gene expression profiling, Knockout mouse, lacZ reporter, Organ Specificity, lcsh:RB1-214
Abstract

Knowledge of the expression profile of a gene is a critical piece of information required to build an understanding of the normal and essential functions of that gene and any role it may play in the development or progression of disease. High-throughput, large-scale efforts are on-going internationally to characterise reporter-tagged knockout mouse lines. As part of that effort, we report an open access adult mouse expression resource, in which the expression profile of 424 genes has been assessed in up to 47 different organs, tissues and sub-structures using a lacZ reporter gene. Many specific and informative expression patterns were noted. Expression was most commonly observed in the testis and brain and was most restricted in white adipose tissue and mammary gland. Over half of the assessed genes presented with an absent or localised expression pattern (categorised as 0-10 positive structures). A link between complexity of expression profile and viability of homozygous null animals was observed; inactivation of genes expressed in ≥21 structures was more likely to result in reduced viability by postnatal day 14 compared with more restricted expression profiles. For validation purposes, this mouse expression resource was compared with Bgee, a federated composite of RNA-based expression data sets. Strong agreement was observed, indicating a high degree of specificity in our data. Furthermore, there were 1207 observations of expression of a particular gene in an anatomical structure where Bgee had no data, indicating a large amount of novelty in our data set. Examples of expression data corroborating and extending genotype-phenotype associations and supporting disease gene candidacy are presented to demonstrate the potential of this powerful resource., Editor's Choice: The report presents an open-access adult mouse expression resource, in which the expression profile of 424 genes has been assessed in up to 47 different organs, tissues and sub-structures using a lacZ reporter gene.

Published
2015

44. Adhesives for on-site bonding: characteristics, testing and prospects

Author

Pizzo B. and Smedley D.

Subjects
Epoxy resins, Polyurethanes, Phenol-resorcinol-formaldehyde (PRF) resins, formulation, long-term duration, timber, structural wood
Abstract

The present chapter deals with the main characteristics of those adhesive products normally used for the reinforcement of timber structures, generally achieved through a site-applied bonding procedure. The characteristics relate to a combination of the chemical composition and the formulation characteristics of the products. A section dealing with testing procedures specifically intended for products to be used on site has also been added, as this aspect does not exist in current European standards. The principal issues associated with the use of those products, mainly relating to long-term duration aspects, are considered, providing more of the adhesive characteristics and features of the adhesive rather than the wood substrate. Finally, some challenges are introduced in order to improve research in this field.

Published
2015

45. The BioMart community portal: An innovative alternative to large, centralized data repositories

Author

Smedley, D, Haider, S, Durinck, S, Pandini, L, Provero, P, Allen, J, Arnaiz, O, Awedh, MH, Baldock, R, Barbiera, G, Bardou, P, Beck, T, Blake, A, Bonierbale, M, Brookes, AJ, Bucci, G, Buetti, I, Burge, S, Cabau, C, Carlson, JW, Chelala, C, Chrysostomou, C, Cittaro, D, Collin, O, Cordova, R, Cutts, RJ, Dassi, E, Di Genova, A, Djari, A, Esposito, A, Estrella, H, Eyras, E, Fernandez-Banet, J, Forbes, S, Free, RC, Fujisawa, T, Gadaleta, E, Garcia-Manteiga, JM, Goodstein, D, Gray, K, Guerra-Assunção, JA, Haggarty, B, Han, DJ, Han, BW, Harris, T, Harshbarger, J, Hastings, RK, Hayes, RD, Hoede, C, Hu, S, Hu, ZL, Hutchins, L, Kan, Z, Kawaji, H, Keliet, A, Kerhornou, A, Kim, S, Kinsella, R, Klopp, C, Kong, L, Lawson, D, Lazarevic, D, Lee, JH, Letellier, T, Li, CY, Lio, P, Liu, CJ, Luo, J, Maass, A, Mariette, J, Maurel, T, Merella, S, Mohamed, AM, Moreews, F, Nabihoudine, I, Ndegwa, N, Noirot, C, Perez-Llamas, C, Primig, M, Quattrone, A, Quesneville, H, Rambaldi, D, Reecy, J, Riba, M, Rosanoff, S, Saddiq, AA, Salas, E, Sallou, O, Shepherd, R, Simon, R, and Sperling, L

Abstract

© 2015 The Author(s). The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.

Published
2015

46. Deletions of chromosomal regulatory boundaries are associated with congenital disease

Author

Ibn-Salem, J., Köhler, S., Love, M., Chung, H., Huang, N., Hurles, M., Haendel, M., Washington, N., Smedley, D., Mungall, C., Lewis, S., Ott, C., Bauer, S., Schofield, P., Mundlos, S., Spielmann, M., and Robinson, P.

Subjects
DNA Copy Number Variations, Models, Genetic, Genome, Human, Research, Gene Dosage, Genetic Diseases, Inborn, Molecular Sequence Annotation, Genomics, Haploinsufficiency, Gene Ontology, Phenotype, Databases, Genetic, Chromosomes, Human, Humans, Sequence Deletion
Abstract

Background Recent data from genome-wide chromosome conformation capture analysis indicate that the human genome is divided into conserved megabase-sized self-interacting regions called topological domains. These topological domains form the regulatory backbone of the genome and are separated by regulatory boundary elements or barriers. Copy-number variations can potentially alter the topological domain architecture by deleting or duplicating the barriers and thereby allowing enhancers from neighboring domains to ectopically activate genes causing misexpression and disease, a mutational mechanism that has recently been termed enhancer adoption. Results We use the Human Phenotype Ontology database to relate the phenotypes of 922 deletion cases recorded in the DECIPHER database to monogenic diseases associated with genes in or adjacent to the deletions. We identify combinations of tissue-specific enhancers and genes adjacent to the deletion and associated with phenotypes in the corresponding tissue, whereby the phenotype matched that observed in the deletion. We compare this computationally with a gene-dosage pathomechanism that attempts to explain the deletion phenotype based on haploinsufficiency of genes located within the deletions. Up to 11.8% of the deletions could be best explained by enhancer adoption or a combination of enhancer adoption and gene-dosage effects. Conclusions Our results suggest that enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0423-1) contains supplementary material, which is available to authorized users.

Published
2014

47. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome

Author

Zemojtel, T, Kahler, S, Mackenroth, L, Jager, M, Hecht, J, Krawitz, P, Graul-Neumann, L, Doelken, S, Ehmke, N, Spielmann, M, Christine, N, Schweiger, M, Krager, U, Frommer, G, Fischer, B, Kornak, U, Ardeshirdavani, Amin, Moreau, Yves, Lewis, S, Haendel, M, Smedley, D, Horn, D, Mundlos, S, and NRobinson, P

Subjects
SISTA
Abstract

Less than half of patients with suspected genetic disease receive a molecular diagnosis. We have therefore integrated next-generation sequencing (NGS), bioinformatics, and clinical data into an effective diagnostic workflow. We used variants in the 2741 established Mendelian disease genes [the disease-associated genome (DAG)] to develop a targeted enrichment DAG panel (7.1 Mb), which achieves a coverage of 20-fold or better for 98% of bases. Furthermore, we established a computational method [Phenotypic Interpretation of eXomes (PhenIX)] that evaluated and ranked variants based on pathogenicity and semantic similarity of patients' phenotype described by Human Phenotype Ontology (HPO) terms to those of 3991 Mendelian diseases. In computer simulations, ranking genes based on the variant score put the true gene in first place less than 5% of the time; PhenIX placed the correct gene in first place more than 86% of the time. In a retrospective test of PhenIX on 52 patients with previously identified mutations and known diagnoses, the correct gene achieved a mean rank of 2.1. In a prospective study on 40 individuals without a diagnosis, PhenIX analysis enabled a diagnosis in 11 cases (28%, at a mean rank of 2.4). Thus, the NGS of the DAG followed by phenotype-driven bioinformatic analysis allows quick and effective differential diagnostics in medical genetics. ispartof: Science Translational Medicine vol:6 issue:252 pages:123-125 ispartof: location:United States status: published

Published
2014

48. Automatic concept recognition using the Human Phenotype Ontology reference and test suite corpora

Author

Groza, T., Kohler, S., Doelken, S., Collier, N., Oellrich, A., Smedley, D., Couto, F.M., Baynam, G., Zankl, A., Robinson, P.N., Groza, T., Kohler, S., Doelken, S., Collier, N., Oellrich, A., Smedley, D., Couto, F.M., Baynam, G., Zankl, A., and Robinson, P.N.

Abstract

Concept recognition tools rely on the availability of textual corpora to assess their performance and enable the identification of areas for improvement. Typically, corpora are developed for specific purposes, such as gene name recognition. Gene and protein name identification are longstanding goals of biomedical text mining, and therefore a number of different corpora exist. However, phenotypes only recently became an entity of interest for specialized concept recognition systems, and hardly any annotated text is available for performance testing and training. Here, we present a unique corpus, capturing text spans from 228 abstracts manually annotated with Human Phenotype Ontology (HPO) concepts and harmonized by three curators, which can be used as a reference standard for free text annotation of human phenotypes. Furthermore, we developed a test suite for standardized concept recognition error analysis, incorporating 32 different types of test cases corresponding to 2164 HPO concepts. Finally, three established phenotype concept recognizers (NCBO Annotator, OBO Annotator and Bio-LarK CR) were comprehensively evaluated, and results are reported against both the text corpus and the test suites. The gold standard and test suites corpora are available from http://bio-lark.org/hpo_res.html.

Published
2015

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