- Main
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease
- Carss, Keren J;
- Arno, Gavin;
- Erwood, Marie;
- Stephens, Jonathan;
- Sanchis-Juan, Alba;
- Hull, Sarah;
- Megy, Karyn;
- Grozeva, Detelina;
- Dewhurst, Eleanor;
- Malka, Samantha;
- Plagnol, Vincent;
- Penkett, Christopher;
- Stirrups, Kathleen;
- Rizzo, Roberta;
- Wright, Genevieve;
- Josifova, Dragana;
- Bitner-Glindzicz, Maria;
- Scott, Richard H;
- Clement, Emma;
- Allen, Louise;
- Armstrong, Ruth;
- Brady, Angela F;
- Carmichael, Jenny;
- Chitre, Manali;
- Henderson, Robert HH;
- Hurst, Jane;
- MacLaren, Robert E;
- Murphy, Elaine;
- Paterson, Joan;
- Rosser, Elisabeth;
- Thompson, Dorothy A;
- Wakeling, Emma;
- Ouwehand, Willem H;
- Michaelides, Michel;
- Moore, Anthony T;
- Consortium, NIHR-BioResource Rare Diseases;
- Aitman, Timothy;
- Alachkar, Hana;
- Ali, Sonia;
- Allen, Louise;
- Allsup, David;
- Ambegaonkar, Gautum;
- Anderson, Julie;
- Antrobus, Richard;
- Armstrong, Ruth;
- Arno, Gavin;
- Arumugakani, Gururaj;
- Ashford, Sofie;
- Astle, William;
- Attwood, Antony;
- Austin, Steve;
- Bacchelli, Chiara;
- Bakchoul, Tamam;
- Bariana, Tadbir K;
- Baxendale, Helen;
- Bennett, David;
- Bethune, Claire;
- Bibi, Shahnaz;
- Bitner-Glindzicz, Maria;
- Bleda, Marta;
- Boggard, Harm;
- Bolton-Maggs, Paula;
- Booth, Claire;
- Bradley, John R;
- Brady, Angie;
- Brown, Matthew;
- Browning, Michael;
- Bryson, Christine;
- Burns, Siobhan;
- Calleja, Paul;
- Canham, Natalie;
- Carmichael, Jenny;
- Carss, Keren;
- Caulfield, Mark;
- Chalmers, Elizabeth;
- Chandra, Anita;
- Chinnery, Patrick;
- Chitre, Manali;
- Church, Colin;
- Clement, Emma;
- Clements-Brod, Naomi;
- Clowes, Virginia;
- Coghlan, Gerry;
- Collins, Peter;
- Cooper, Nichola;
- Creaser-Myers, Amanda;
- DaCosta, Rosa;
- Daugherty, Louise;
- Davies, Sophie;
- Davis, John;
- De Vries, Minka;
- Deegan, Patrick;
- Deevi, Sri VV;
- Deshpande, Charu;
- Devlin, Lisa;
- Dewhurst, Eleanor;
- Doffinger, Rainer;
- Dormand, Natalie;
- Drewe, Elizabeth;
- Edgar, David;
- Egner, William;
- Erber, Wendy N;
- Erwood, Marie;
- Everington, Tamara;
- Favier, Remi;
- Firth, Helen;
- Fletcher, Debra;
- Flinter, Frances;
- Fox, James C;
- Frary, Amy;
- Freson, Kathleen;
- Furie, Bruce;
- Furnell, Abigail;
- Gale, Daniel;
- Gardham, Alice;
- Gattens, Michael;
- Ghali, Neeti;
- Ghataorhe, Pavandeep K;
- Ghurye, Rohit;
- Gibbs, Simon;
- Gilmour, Kimberley;
- Gissen, Paul;
- Goddard, Sarah;
- Gomez, Keith;
- Gordins, Pavel;
- Gräf, Stefan;
- Greene, Daniel;
- Greenhalgh, Alan;
- Greinacher, Andreas;
- Grigoriadou, Sofia;
- Grozeva, Detelina;
- Hackett, Scott;
- Hadinnapola, Charaka;
- Hague, Rosie;
- Haimel, Matthias;
- Halmagyi, Csaba;
- Hammerton, Tracey;
- Hart, Daniel;
- Hayman, Grant;
- Heemskerk, Johan WM;
- Henderson, Robert;
- Hensiek, Anke;
- Henskens, Yvonne;
- Herwadkar, Archana;
- Holden, Simon;
- Holder, Muriel;
- Holder, Susan;
- Hu, Fengyuan;
- Huissoon, Aarnoud;
- Humbert, Marc;
- Hurst, Jane;
- James, Roger;
- Jolles, Stephen;
- Josifova, Dragana;
- Kazmi, Rashid;
- Keeling, David;
- Kelleher, Peter;
- Kelly, Anne M;
- Kennedy, Fiona;
- Kiely, David;
- Kingston, Nathalie;
- Koziell, Ania;
- Krishnakumar, Deepa;
- Kuijpers, Taco W;
- Kumararatne, Dinakantha;
- Kurian, Manju;
- Laffan, Michael A;
- Lambert, Michele P;
- Allen, Hana Lango;
- Lawrie, Allan;
- Lear, Sara;
- Lees, Melissa;
- Lentaigne, Claire;
- Liesner, Ri;
- Linger, Rachel;
- Longhurst, Hilary;
- Lorenzo, Lorena;
- Machado, Rajiv;
- Mackenzie, Rob;
- MacLaren, Robert;
- Maher, Eamonn;
- Maimaris, Jesmeen;
- Mangles, Sarah;
- Manson, Ania;
- Mapeta, Rutendo;
- Markus, Hugh S;
- Martin, Jennifer;
- Masati, Larahmie;
- Mathias, Mary;
- Matser, Vera;
- Maw, Anna;
- McDermott, Elizabeth;
- McJannet, Coleen;
- Meacham, Stuart;
- Meehan, Sharon;
- Megy, Karyn;
- Mehta, Sarju;
- Michaelides, Michel;
- Millar, Carolyn M;
- Moledina, Shahin;
- Moore, Anthony;
- Morrell, Nicholas;
- Mumford, Andrew;
- Murng, Sai;
- Murphy, Elaine;
- Nejentsev, Sergey;
- Noorani, Sadia;
- Nurden, Paquita;
- Oksenhendler, Eric;
- Ouwehand, Willem H;
- Papadia, Sofia;
- Park, Soo-Mi;
- Parker, Alasdair;
- Pasi, John;
- Patch, Chris;
- Paterson, Joan;
- Payne, Jeanette;
- Peacock, Andrew;
- Peerlinck, Kathelijne;
- Penkett, Christopher J;
- Pepke-Zaba, Joanna;
- Perry, David J;
- Pollock, Val;
- Polwarth, Gary;
- Ponsford, Mark;
- Qasim, Waseem;
- Quinti, Isabella;
- Rankin, Stuart;
- Rankin, Julia;
- Raymond, F Lucy;
- Rehnstrom, Karola;
- Reid, Evan;
- Rhodes, Christopher J;
- Richards, Michael;
- Richardson, Sylvia;
- Richter, Alex;
- Roberts, Irene;
- Rondina, Matthew;
- Rosser, Elisabeth;
- Roughley, Catherine;
- Rue-Albrecht, Kevin;
- Samarghitean, Crina;
- Sanchis-Juan, Alba;
- Sandford, Richard;
- Santra, Saikat;
- Sargur, Ravishankar;
- Savic, Sinisa;
- Schulman, Sol;
- Schulze, Harald;
- Scott, Richard;
- Scully, Marie;
- Seneviratne, Suranjith;
- Sewell, Carrock;
- Shamardina, Olga;
- Shipley, Debbie;
- Simeoni, Ilenia;
- Sivapalaratnam, Suthesh;
- Smith, Kenneth;
- Sohal, Aman;
- Southgate, Laura;
- Staines, Simon;
- Staples, Emily;
- Stauss, Hans;
- Stein, Penelope;
- Stephens, Jonathan;
- Stirrups, Kathleen;
- Stock, Sophie;
- Suntharalingam, Jay;
- Tait, R Campbell;
- Talks, Kate;
- Tan, Yvonne;
- Thachil, Jecko;
- Thaventhiran, James;
- Thomas, Ellen;
- Thomas, Moira;
- Thompson, Dorothy;
- Thrasher, Adrian;
- Tischkowitz, Marc;
- Titterton, Catherine;
- Toh, Cheng-Hock;
- Toshner, Mark;
- Treacy, Carmen;
- Trembath, Richard;
- Tuna, Salih;
- Turek, Wojciech;
- Turro, Ernest;
- Van Geet, Chris;
- Veltman, Marijke;
- Vogt, Julie;
- von Ziegenweldt, Julie;
- Noordegraaf, Anton Vonk;
- Wakeling, Emma;
- Wanjiku, Ivy;
- Warner, Timothy Q;
- Wassmer, Evangeline;
- Watkins, Hugh;
- Webster, Andrew;
- Welch, Steve;
- Westbury, Sarah;
- Wharton, John;
- Whitehorn, Deborah;
- Wilkins, Martin;
- Willcocks, Lisa;
- Williamson, Catherine;
- Woods, Geoffrey;
- Wort, John;
- Yeatman, Nigel;
- Yong, Patrick;
- Young, Tim;
- Yu, Ping;
- Webster, Andrew R;
- Raymond, F Lucy
- et al.
Published Web Location
https://doi.org/10.1016/j.ajhg.2016.12.003Abstract
Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
Enter the password to open this PDF file:
-
-
-
-
-
-
-
-
-
-
-
-
-
-