1,527 results on '"Keane, Thomas"'
Search Results
202. Structural Variation Shapes the Landscape of Recombination in Mouse
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Morgan, Andrew P, primary, Gatti, Daniel M, additional, Najarian, Maya L, additional, Keane, Thomas M, additional, Galante, Raymond J, additional, Pack, Allan I, additional, Mott, Richard, additional, Churchill, Gary A, additional, and de Villena, Fernando Pardo-Manuel, additional
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- 2017
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203. The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II)
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Crawford, E. David, primary, Petrylak, Daniel P., additional, Shore, Neal, additional, Saad, Fred, additional, Slovin, Susan F., additional, Vogelzang, Nicholas J., additional, Keane, Thomas E., additional, Koo, Phillip J., additional, Gomella, Leonard G., additional, O'Sullivan, Joe M., additional, Tombal, Bertrand, additional, Concepcion, Raoul S., additional, Sieber, Paul, additional, Stone, Nelson N., additional, Finkelstein, Steven E., additional, and Yu, Evan Y., additional
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- 2017
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204. The potential role of follicle-stimulating hormone in the cardiovascular, metabolic, skeletal, and cognitive effects associated with androgen deprivation therapy
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Crawford, E. David, primary, Schally, Andrew V., additional, Pinthus, Jehonathan H., additional, Block, Norman L., additional, Rick, Ferenc G., additional, Garnick, Marc B., additional, Eckel, Robert H., additional, Keane, Thomas E., additional, Shore, Neal D., additional, Dahdal, David N., additional, Beveridge, Thomas J.R., additional, and Marshall, Dennis C., additional
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- 2017
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205. Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated
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Ibarra-Soria, Ximena, primary, Nakahara, Thiago S, additional, Lilue, Jingtao, additional, Jiang, Yue, additional, Trimmer, Casey, additional, Souza, Mateus AA, additional, Netto, Paulo HM, additional, Ikegami, Kentaro, additional, Murphy, Nicolle R, additional, Kusma, Mairi, additional, Kirton, Andrea, additional, Saraiva, Luis R, additional, Keane, Thomas M, additional, Matsunami, Hiroaki, additional, Mainland, Joel, additional, Papes, Fabio, additional, and Logan, Darren W, additional
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- 2017
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- View/download PDF
206. PD28-02 THE IMPACT OF CLINICAL CCP TESTING IN MEN WITH LOCALIZED PROSTATE CANCER FOR EXPANDING THE POPULATION OF MEN ELIGIBLE FOR ACTIVE SURVEILLANCE
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Ehdaie, Behfar, primary, Stone, Steve, additional, Bernhisel, Ryan, additional, Eastham, James, additional, Keane, Thomas, additional, Davis, John, additional, Crawford, E David, additional, Brawer, Michael, additional, Lin, Daniel, additional, and Scardino, Peter, additional
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- 2017
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207. PD61-08 DOES GLEASON SCORE AT THE SITE OF POSITIVE SURGICAL MARGIN PREDICT RECURRENCE FOLLOWING RADICAL PROSTATECTOMY?
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Rac, Goran, primary, Dagrosa, Lawrence, additional, Spruill, Laura, additional, and Keane, Thomas, additional
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- 2017
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- View/download PDF
208. Author response: Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated
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Ibarra-Soria, Ximena, primary, Nakahara, Thiago S, additional, Lilue, Jingtao, additional, Jiang, Yue, additional, Trimmer, Casey, additional, Souza, Mateus AA, additional, Netto, Paulo HM, additional, Ikegami, Kentaro, additional, Murphy, Nicolle R, additional, Kusma, Mairi, additional, Kirton, Andrea, additional, Saraiva, Luis R, additional, Keane, Thomas M, additional, Matsunami, Hiroaki, additional, Mainland, Joel, additional, Papes, Fabio, additional, and Logan, Darren W, additional
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- 2017
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209. Abstract PR11: The molecular implications of lifestyle associated metabolites (AGEs) to prostate cancer disparity
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Smith, Danzell, primary, Foster, Dion, additional, Spruill, Laura, additional, Nogueira, Lourdes, additional, Krisanits, Bradley, additional, Cramer, Scott, additional, Ford, Marvella, additional, Savage, Stephen, additional, Keane, Thomas, additional, Findlay, Victoria, additional, and Turner, David, additional
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- 2017
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- View/download PDF
210. Whole-exome sequencing of 228 patients with sporadic Parkinson’s disease
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Sandor, Cynthia, primary, Honti, Frantisek, additional, Haerty, Wilfried, additional, Szewczyk-Krolikowski, Konrad, additional, Tomlinson, Paul, additional, Evetts, Sam, additional, Millin, Stephanie, additional, Keane, Thomas, additional, McCarthy, Shane A., additional, Durbin, Richard, additional, Talbot, Kevin, additional, Hu, Michele, additional, Webber, Caleb, additional, Ponting, Chris P., additional, and Wade-Martins, Richard, additional
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- 2017
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211. Truncation of POC1A associated with short stature and extreme insulin resistance
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Chen, Jian Hua, Segni, Maria, Payne, Felicity, Huang-Doran, Isabel, Sleigh, Alison, Adams, Claire, Durbin, Richard, Muddyman, Dawn, Soranzo, Nicole, Timpson, Nic, Spector, Tim, Richards, Bren, Palotie, Aarno, Owen, Michael, Barrett, Jeff, Geschwind, Daniel, Hurles, Matt, Fitzpatrick, David, Barroso, Inês, Farooqi, Sadaf, Zeggini, Eleftheria, Kaye, Jane, Kennedy, Karen, McCarthy, Shane, Stalker, Jim, Langford, Cordelia, Keane, Thomas, Savage, David B., O’Rahilly, Stephen, and Semple, Robert K.
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Adult ,Dyslipidaemia ,Molecular Sequence Data ,Mitosis ,Cell Cycle Proteins ,Dwarfism ,Spindle Apparatus ,Article ,POC1A ,Humans ,Protein Isoforms ,Amino Acid Sequence ,Frameshift Mutation ,Centrioles ,Centrosome ,Primary cilium ,Diabetes ,Cell Cycle ,Facies ,Proteins ,Insulin resistance ,Centriole ,centriole ,centrosome ,diabetes ,dyslipidaemia ,insulin resistance ,primary cilium ,short stature ,skeletal dysplasia ,Body Height ,Fatty Liver ,Short stature ,Cytoskeletal Proteins ,Skeletal dysplasia ,Female ,Insulin Resistance ,Sequence Alignment - Abstract
We describe a female proband with primordial dwarfism, skeletal dysplasia, facial dysmorphism, extreme dyslipidaemic insulin resistance and fatty liver associated with a novel homozygous frameshift mutation in POC1A, predicted to affect two of the three protein products of the gene. POC1A encodes a protein associated with centrioles throughout the cell cycle and implicated in both mitotic spindle and primary ciliary function. Three homozygous mutations affecting all isoforms of POC1A have recently been implicated in a similar syndrome of primordial dwarfism, although no detailed metabolic phenotypes were described. Primary cells from the proband we describe exhibited increased centrosome amplification and multipolar spindle formation during mitosis, but showed normal DNA content, arguing against mitotic skipping, cleavage failure or cell fusion. Despite evidence of increased DNA damage in cells with supernumerary centrosomes, no aneuploidy was detected. Extensive centrosome clustering both at mitotic spindles and in primary cilia mitigated the consequences of centrosome amplification, and primary ciliary formation was normal. Although further metabolic studies of patients with POC1A mutations are warranted, we suggest that POC1A may be added to ALMS1 and PCNT as examples of centrosomal or pericentriolar proteins whose dysfunction leads to extreme dyslipidaemic insulin resistance. Further investigation of links between these molecular defects and adipose tissue dysfunction is likely to yield insights into mechanisms of adipose tissue maintenance and regeneration that are critical to metabolic health.
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- 2015
212. Using reference-free compressed data structures to analyze sequencing reads from thousands of human genomes
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Dolle, Dirk D., primary, Liu, Zhicheng, additional, Cotten, Matthew, additional, Simpson, Jared T., additional, Iqbal, Zamin, additional, Durbin, Richard, additional, McCarthy, Shane A., additional, and Keane, Thomas M., additional
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- 2016
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213. Whole Genome Sequence of Two Wild-Derived Mus musculus domesticus Inbred Strains, LEWES/EiJ and ZALENDE/EiJ, with Different Diploid Numbers
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Morgan, Andrew P, primary, Didion, John P, additional, Doran, Anthony G, additional, Holt, James M, additional, McMillan, Leonard, additional, Keane, Thomas M, additional, and de Villena, Fernando Pardo-Manuel, additional
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- 2016
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214. Chromosome assembly of large and complex genomes using multiple references
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Kolmogorov, Mikhail, primary, Armstrong, Joel, additional, Raney, Brian J., additional, Streeter, Ian, additional, Dunn, Matthew, additional, Yang, Fengtang, additional, Odom, Duncan, additional, Flicek, Paul, additional, Keane, Thomas, additional, Thybert, David, additional, Paten, Benedict, additional, and Pham, Son, additional
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- 2016
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215. Peer review of 'Chromosomer: a reference-based genome arrangement tool for producing draft chromosome sequences'
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Keane, Thomas
- Abstract
This is the open peer reviewers comments and recommendations regarding the submitted GigaScience article and/or dataset.
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- 2015
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216. Insights into the Composition and Function of a Bismuth-Based Catalyst for Reduction of CO2 to CO.
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Atifi, Abderrahman, Keane, Thomas P., DiMeglio, John L., Pupillo, Rachel C., Mullins, David R., Lutterman, Daniel A., and Rosenthal, Joel
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- 2019
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217. Oxidative Degradation of Multi-Carbon Substrates by an Oxidic Cobalt Phosphate Catalyst.
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Keane, Thomas P., Brodsky, Casey N., and Nocera, Daniel G.
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- 2019
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218. Proton-Electron Conductivity in Thin Films of a Cobalt-Oxygen Evolving Catalyst.
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Brodsky, Casey N., Bediako, D. Kwabena, Shi, Chenyang, Keane, Thomas P., Costentin, Cyrille, Billinge, Simon J. L., and Nocera, Daniel G.
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- 2019
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219. The European Nucleotide Archive in 2018.
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Harrison, Peter W, Alako, Blaise, Amid, Clara, Cerdeño-Tárraga, Ana, Cleland, Iain, Holt, Sam, Hussein, Abdulrahman, Jayathilaka, Suran, Kay, Simon, Keane, Thomas, Leinonen, Rasko, Liu, Xin, Martínez-Villacorta, Josué, Milano, Annalisa, Pakseresht, Nima, Rajan, Jeena, Reddy, Kethi, Richards, Edward, Rosello, Marc, and Silvester, Nicole
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- 2019
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220. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.
- Author
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UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Evans, Christopher P, Higano, Celestia S, Keane, Thomas, Andriole, Gerald, Saad, Fred, Iversen, Peter, Miller, Kurt, Kim, Choung-Soo, Kimura, Go, Armstrong, Andrew J, Sternberg, Cora N, Loriot, Yohann, de Bono, Johann, Noonberg, Sarah B, Mansbach, Hank, Bhattacharya, Suman, Perabo, Frank, Beer, Tomasz M, Tombal, Bertrand, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Evans, Christopher P, Higano, Celestia S, Keane, Thomas, Andriole, Gerald, Saad, Fred, Iversen, Peter, Miller, Kurt, Kim, Choung-Soo, Kimura, Go, Armstrong, Andrew J, Sternberg, Cora N, Loriot, Yohann, de Bono, Johann, Noonberg, Sarah B, Mansbach, Hank, Bhattacharya, Suman, Perabo, Frank, Beer, Tomasz M, and Tombal, Bertrand
- Abstract
BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. OBJECTIVE: To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. DESIGN, SETTING, AND PARTICIPANTS: One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195). INTERVENTION: Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. RESULTS AND LIMITATIONS: Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. CONCLUSIONS: Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only diseas
- Published
- 2016
221. The PREVAIL Study:Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer
- Author
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Evans, Christopher P, Higano, Celestia S, Keane, Thomas, Andriole, Gerald, Saad, Fred, Iversen, Peter, Miller, Kurt, Kim, Choung-Soo, Kimura, Go, Armstrong, Andrew J, Sternberg, Cora N, Loriot, Yohann, de Bono, Johann S, Noonberg, Sarah B, Mansbach, Hank, Bhattacharya, Suman, Perabo, Frank, Beer, Tomasz M, Tombal, Bertrand, Evans, Christopher P, Higano, Celestia S, Keane, Thomas, Andriole, Gerald, Saad, Fred, Iversen, Peter, Miller, Kurt, Kim, Choung-Soo, Kimura, Go, Armstrong, Andrew J, Sternberg, Cora N, Loriot, Yohann, de Bono, Johann S, Noonberg, Sarah B, Mansbach, Hank, Bhattacharya, Suman, Perabo, Frank, Beer, Tomasz M, and Tombal, Bertrand
- Abstract
BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer.OBJECTIVE: To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease.DESIGN, SETTING, AND PARTICIPANTS: One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195).INTERVENTION: Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc.RESULTS AND LIMITATIONS: Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease.CONCLUSIONS: Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or hig
- Published
- 2016
222. Perioperative hormonal therapy in locally advanced adenocarcinoma of the prostate
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Graham, Sam D., Jr., Keane, Thomas E., Petros, John A., and Sanders, W. Holt
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Prostate cancer -- Care and treatment ,Hormone therapy -- Evaluation ,Health - Abstract
Perioperative hormonal therapy is a potential therapeutic strategy that combines the advantages of systemic therapy and local surgical control of adenocarcinoma of the prostate. In most cases, the use of hormonal therapy causes a reduction in the size of the prostate, some potential reduction in the volume of the cancer, and varying success in downstaying of the malignancy. No study has shown any benefit in either survival or reduction of recurrences. Cancer 1995; 75:1969-71.
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- 1995
223. Chronic calcific pancreatitis: combination ERCP and extracorporeal shock wave lithotripsy for pancreatic duct stones
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Lawrence, Christopher, Siddiqi, M. Faisal, Hamilton, Jonathan N., Keane, Thomas E., Romagnuolo, Joseph, Hawes, Robert H., and Cotton, Peter B.
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Pancreatitis -- Diagnosis ,Pancreatitis -- Care and treatment ,Pancreatitis -- Research ,Endoscopic retrograde cholangiopancreatography -- Usage ,Endoscopic retrograde cholangiopancreatography -- Research ,Lithotripsy -- Usage ,Lithotripsy -- Patient outcomes ,Lithotripsy -- Research ,Calculi -- Care and treatment ,Calculi -- Research ,Abdominal pain -- Care and treatment ,Abdominal pain -- Research ,Health - Published
- 2010
224. Identification of structural variation in mouse genomes
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Keane Thomas, Wong Kim, Adams David, Flint Jonathan, Reymond Alexandre, Yalcin Binnaz, Dupuis, Christine, The Wellcome Trust Sanger Institute [Cambridge], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV] Life Sciences [q-bio] ,Heterogeneous Stock (HS) ,Sanger Mouse Genomes Project ,array comparative genome hybridization (aCGH) ,inbred strains of mice ,next-generation sequencing (NGS) ,paired-end mapping (PEM) ,structural variation (SV) ,[SDV]Life Sciences [q-bio] ,Genetics ,Review Article - Abstract
International audience; Structural variation is variation in structure of DNA regions affecting DNA sequence length and/or orientation. It generally includes deletions, insertions, copy-number gains, inversions, and transposable elements. Traditionally, the identification of structural variation in genomes has been challenging. However, with the recent advances in high-throughput DNA sequencing and paired-end mapping (PEM) methods, the ability to identify structural variation and their respective association to human diseases has improved considerably. In this review, we describe our current knowledge of structural variation in the mouse, one of the prime model systems for studying human diseases and mammalian biology. We further present the evolutionary implications of structural variation on transposable elements. We conclude with future directions on the study of structural variation in mouse genomes that will increase our understanding of molecular architecture and functional consequences of structural variation.
- Published
- 2014
225. Using BWT structures for reference-free querying of the 1000 Genomes sequence data
- Author
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Keane, Thomas, Zhicheng Liu, McCarthy, Shane, Simpson, Jared, Iqbal, Zamin, and Durbin, Richard
- Abstract
Using BWT structures for reference-free querying ofthe 1000 Genomes sequence data
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- 2014
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226. Genomes and phenomes of a population of outbred rats and its progenitors
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Baud, Amelie, Guryev, Victor, Hummel, Oliver, Johannesson, Martina, Hermsen, Roel, Stridh, Pernilla, Graham, Delyth, McBride, Martin W., Foroud, Tatiana, Calderari, Sophie, Diez, Margarita, Ockinger, Johan, Beyeen, Amennai D., Gillett, Alan, Abdelmagid, Nada, Guerreiro-Cacais, Andre Ortlieb, Jagodic, Maja, Tuncel, Jonatan, Norin, Ulrika, Beattie, Elisabeth, Huynh, Ngan, Miller, William H., Koller, Daniel L., Alam, Imranul, Falak, Samreen, Osborne-Pellegrin, Mary, Martinez-Membrives, Esther, Canete, Toni, Blazquez, Gloria, Vicens-Costa, Elia, Mont-Cardona, Carme, Diaz-Moran, Sira, Tobena, Adolf, Zelenika, Diana, Saar, Kathrin, Patone, Giannino, Bauerfeind, Anja, Bihoreau, Marie-Therese, Heinig, Matthias, Lee, Young-Ae, Rintisch, Carola, Schulz, Herbert, Wheeler, David A., Worley, Kim C., Muzny, Donna M., Gibbs, Richard A., Lathrop, Mark, Lansu, Nico, Toonen, Pim, Ruzius, Frans Paul, de Bruijn, Ewary, Hauser, Heidi, Adams, David J., Keane, Thomas, Atanur, Santosh s., Aitman, Tim J., Flicek, Paul, Malinauskas, Tomas, Jones, E Yvonne, Ekman, Diana, Lopez-Aumatell, Regina, Dominiczak, Anna F., Holmdahl, Rikard, Olsson, Tomas, Gauguier, Dominique, Hubner, Norbert, Fernandez-Teruel, Alberto, Cuppen, Edwin, Mott, Richard, and Flint, Jonathan
- Abstract
Finding genetic variants that contribute to phenotypic variation is one of the main challenges of modern genetics. We used an outbred population of rats (Heterogeneous Stock, HS) in a combined sequence-based and genetic mapping analysis to identify sequence variants and genes contributing to complex traits of biomedical relevance. Here we describe the sequences of the eight inbred progenitors of the HS and the variants that segregate between them. We report the genotyping of 1,407 HS rats, and the collection from 2,006 rats of 195 phenotypic measures that are relevant to models of anxiety, type 2 diabetes, hypertension and osteoporosis. We make available haplotype dosages for the 1,407 genotyped rats, since genetic mapping in the HS is best carried out by reconstructing each HS chromosome as a mosaic of the progenitor genomes. Finally, we have deposited an R object that makes it easy to incorporate our sequence data into any genetic study of HS rats. Our genetic data are available for both Rnor3.4 and Rnor5.0 rat assemblies.
- Published
- 2014
227. 1,000 Genomes and UK10K Analysis Pipelines
- Author
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Mccarthy, Shane, Sendu Bala, Danecek, Petr, Stalker, James, Keane, Thomas, and Durbin, Richard
- Abstract
The 1,000 Genomes and UK10K projects are two large scale sequencing projects with the aim of identifying low frequency genetic variations in the human population. The 1,000 Genomes Project is sequencing the genomes of over 1,000 individuals from populations around the world looking far variants with a frequency of around 1%, while the UK10K Project aims to improve this to 0.1% by sequencing the genomes of over 10,000 individuals from the UK. Large amounts of low-coverage whole-genome and high- coverage exome targeted sequence is being generated using next-generation sequencing technologies; the UK10K project is expected to generate about 100Tbp of raw sequence. We present our solutions to deal with some of the bioinformatics challenges posed by the size and scope of these projects.
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- 2014
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228. Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene
- Author
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Maguire, Simon, Estabel, Jeanne, Ingham, Neil, Pearson, Selina, Ryder, Edward, Carragher, Damian M, Walker, Nicolas, Sanger MGP Slc25a21 Project Team, Bussell, James, Chan, Wai-In, Keane, Thomas M, Adams, David J, Scudamore, Cheryl L, Lelliott, Christopher J, Ramírez-Solis, Ramiro, Karp, Natasha A, Steel, Karen P, White, Jacqueline K, Gerdin, Anna-Karin, Estabel, Jeanne [0000-0002-4472-3820], Lelliott, Christopher [0000-0001-8087-4530], and Apollo - University of Cambridge Repository
- Subjects
Male ,Physiology ,Gene Expression ,medicine.disease_cause ,Mitochondrial Membrane Transport Proteins ,Exon ,Mice ,0302 clinical medicine ,Morphogenesis ,Medicine and Health Sciences ,Paired Box Transcription Factors ,Immune Response ,Genetics ,Regulation of gene expression ,Dicarboxylic Acid Transporters ,Mice, Knockout ,0303 health sciences ,Mutation ,Multidisciplinary ,Homozygote ,Exons ,Animal Models ,Phenotype ,Electrophysiology ,Knockout mouse ,Medicine ,Female ,Anatomy ,Genetic Engineering ,Signal Transduction ,Research Article ,Histology ,Science ,Immunology ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Model Organisms ,medicine ,Animals ,Humans ,Allele ,Alleles ,030304 developmental biology ,Inflammation ,Immunity ,Membrane Transport Proteins ,Biology and Life Sciences ,Otitis Media ,Targeted Mutation ,Gene Expression Regulation ,Genetics of Disease ,Clinical Immunology ,PAX9 Transcription Factor ,Mouth Abnormalities ,Gene Function ,PAX9 ,Animal Genetics ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Homozygosity for Slc25a21(tm1a(KOMP)Wtsi) results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMP)Wtsi) despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMP)Wtsi) and Slc25a21(tm1d(KOMP)Wtsi) alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms.
- Published
- 2013
229. Need for mature evidence to validate HIFU
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Keane, Thomas E. and Bong, Gary W.
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Technology application ,Prostate cancer -- Care and treatment ,Cancer -- Care and treatment ,Cancer -- Technology application ,Ultrasonic waves -- Health aspects ,Ultrasonic waves -- Usage ,Ultrasonic waves -- Technology application - Abstract
The authors provide an excellent review on high-intensity focused ultrasound (HIFU) technology and present an update on the latest efficacy and safety data relating to the treatment of prostate cancer. [...]
- Published
- 2008
230. Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells
- Author
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Forment, Josep V, primary, Herzog, Mareike, additional, Coates, Julia, additional, Konopka, Tomasz, additional, Gapp, Bianca V, additional, Nijman, Sebastian M, additional, Adams, David J, additional, Keane, Thomas M, additional, and Jackson, Stephen P, additional
- Published
- 2016
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- View/download PDF
231. Striking differences in patterns of germline mutation between mice and humans
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Lindsay, Sarah J., primary, Rahbari, Raheleh, additional, Kaplanis, Joanna, additional, Keane, Thomas, additional, and Hurles, Matthew E., additional
- Published
- 2016
- Full Text
- View/download PDF
232. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer
- Author
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Evans, Christopher P., primary, Higano, Celestia S., additional, Keane, Thomas, additional, Andriole, Gerald, additional, Saad, Fred, additional, Iversen, Peter, additional, Miller, Kurt, additional, Kim, Choung-Soo, additional, Kimura, Go, additional, Armstrong, Andrew J., additional, Sternberg, Cora N., additional, Loriot, Yohann, additional, de Bono, Johann, additional, Noonberg, Sarah B., additional, Mansbach, Hank, additional, Bhattacharya, Suman, additional, Perabo, Frank, additional, Beer, Tomasz M., additional, and Tombal, Bertrand, additional
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- 2016
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233. Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated
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Ibarra-Soria, Ximena, primary, Nakahara, Thiago S., additional, Lilue, Jingtao, additional, Jiang, Yue, additional, Trimmer, Casey, additional, Souza, Mateus A. A., additional, Netto, Paulo H. M., additional, Ikegami, Kentaro, additional, Murphy, Nicolle R., additional, Kusma, Mairi, additional, Kirton, Andrea, additional, Saraiva, Luis R., additional, Keane, Thomas M., additional, Matsunami, Hiroaki, additional, Mainland, Joel D., additional, Papes, Fabio, additional, and Logan, Darren W., additional
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- 2016
- Full Text
- View/download PDF
234. Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation and homozygous truncating mutations
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Doran, Anthony G., primary, Wong, Kim, additional, Flint, Jonathan, additional, Adams, David J., additional, Hunter, Kent W., additional, and Keane, Thomas M., additional
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- 2016
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235. An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes
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Bai, Ling, primary, Yang, Howard H., additional, Hu, Ying, additional, Shukla, Anjali, additional, Ha, Ngoc-Han, additional, Doran, Anthony, additional, Faraji, Farhoud, additional, Goldberger, Natalie, additional, Lee, Maxwell P., additional, Keane, Thomas, additional, and Hunter, Kent W., additional
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- 2016
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- View/download PDF
236. Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Trial
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Greiman, Alyssa, primary, Shah, Jaimin, additional, Bhavsar, Robin, additional, Armeson, Kent, additional, Caulder, Susan, additional, Jones, Rabun, additional, Keane, Thomas E., additional, Clarke, Harry S., additional, and Savage, Stephen J., additional
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- 2016
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237. Abstract IA21: An integrated genome-wide systems genetics screen for breast cancer metastasis susceptibility genes
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Hunter, Kent W., primary, Bai, Ling, additional, Yang, Howard H., additional, Hu, Ying, additional, Shukla, Anjali, additional, Ha, Ngoc-Han, additional, Doran, Anthony, additional, Faraji, Farhoud, additional, Goldberger, Natalie, additional, Lee, Maxwell P., additional, and Keane, Thomas, additional
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- 2016
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238. Application of active surveillance threshold to series of samples submitted for commercial testing.
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Scardino, Peter T., primary, Cuzick, Jack M., additional, Stone, Steve, additional, Evans, Brent, additional, Jorgensen, Matthew R, additional, Eastham, James Andrew, additional, Keane, Thomas E., additional, Davis, John W., additional, Lin, Daniel W., additional, Moul, Judd W., additional, Brawer, Michael K., additional, and Crawford, E. David, additional
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- 2016
- Full Text
- View/download PDF
239. Whole-genome sequence-based analysis of thyroid function
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Taylor, Peter N., Porcu, Eleonora, Chew, Shelby, Campbell, Purdey J., Traglia, Michela, Brown, Suzanne J., Mullin, Benjamin H., Shihab, Hashem A., Min, Josine, Walter, Klaudia, Memari, Yasin, Huang, Jie, Barnes, Michael R., Beilby, John P., Charoen, Pimphen, Danecek, Petr, Dudbridge, Frank, Forgetta, Vincenzo, Greenwood, Celia, Grundberg, Elin, Johnson, Andrew D., Hui, Jennie, Lim, Ee M., McCarthy, Shane, Muddyman, Dawn, Panicker, Vijay, Perry, John R.B., Bell, Jordana T., Yuan, Wei, Relton, Caroline, Gaunt, Tom, Schlessinger, David, Abecasis, Goncalo, Cucca, Francesco, Surdulescu, Gabriela L., Woltersdorf, Wolfram, Zeggini, Eleftheria, Zheng, Hou-Feng, Toniolo, Daniela, Dayan, Colin M., Naitza, Silvia, Walsh, John P., Spector, Tim, Davey Smith, George, Durbin, Richard, Brent Richards, J., Sanna, Serena, Soranzo, Nicole, Timpson, Nicholas J., Wilson, Scott G., Turki, Saeed Al, Anderson, Carl, Anney, Richard, Antony, Dinu, Artigas, Maria Soler, Ayub, Muhammad, Balasubramaniam, Senduran, Barrett, Jeffrey C., Barroso, Inês, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Birney, Ewan, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick, Bounds, Rebecca, Boustred, Chris, Breen, Gerome, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Chen, Lu, Ciampi, Antonio, Cirak, Sebhattin, Clapham, Peter, Clement, Gail, Coates, Guy, Collier, David, Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Day-Williams, Aaron, Day, Ian N.M., Down, Thomas, Du, Yuanping, Dunham, Ian, Edkins, Sarah, Ellis, Peter, Evans, David, Faroogi, Sadaf, Fatemifar, Ghazaleh, Fitzpatrick, David R., Flicek, Paul, Flyod, James, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Geihs, Matthias, Geschwind, Daniel, Griffin, Heather, Grozeva, Detelina, Guo, Xueqin, Guo, Xiaosen, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey, Holmans, Peter, Howie, Bryan, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro, Jackson, David K., Jamshidi, Yalda, Jing, Tian, Joyce, Chris, Kaye, Jane, Keane, Thomas, Keogh, Julia, Kemp, John, Kennedy, Karen, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Liang, Jieqin, Lin, Hong, Li, Rui, Li, Yingrui, Liu, Ryan, Lönnqvist, Jouko, Lopes, Margarida, Lotchkova, Valentina, MacArthur, Daniel, Marchini, Jonathan, Maslen, John, Massimo, Mangino, Mathieson, Iain, Marenne, Gaëlle, McGuffin, Peter, McIntosh, Andrew, McKechanie, Andrew G., McQuillin, Andrew, Metrustry, Sarah, Mitchison, Hannah, Moayyeri, Alireza, Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donnovan, Michael, Onoufriadis, Alexandros, O'Rahilly, Stephen, Oualkacha, Karim, Owen, Michael J., Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Pietilainen, Olli, Plagnol, Vincent, Quaye, Lydia, Quai, Michael A., Raymond, Lucy, Rehnström, Karola, Richards, Brent, Ring, Susan, Ritchie, Graham R.S., Roberts, Nicola, Savage, David B., Scambler, Peter, Schiffels, Stephen, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Sharp, Sally I., Shin, So-Youn, Skuse, David, Small, Kerrin, Southam, Lorraine, Spasic-Boskovic, Olivera, Clair, David St, Stalker, Jim, Stevens, Elizabeth, Pourcian, Beate St, Sun, Jianping, Suvisaari, Jaana, Tachmazidou, Ionna, Tobin, Martin D., Valdes, Ana, Kogelenberg, Margriet Van, Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Wheeler, Elanor, Whyte, Tamieka, Williams, Hywel, Williamson, Kathleen A., Wilson, Crispian, Wong, Kim, Xu, ChangJiang, Yang, Jian, Zhang, Fend, Zhang, Pingbo, Taylor, Peter N., Porcu, Eleonora, Chew, Shelby, Campbell, Purdey J., Traglia, Michela, Brown, Suzanne J., Mullin, Benjamin H., Shihab, Hashem A., Min, Josine, Walter, Klaudia, Memari, Yasin, Huang, Jie, Barnes, Michael R., Beilby, John P., Charoen, Pimphen, Danecek, Petr, Dudbridge, Frank, Forgetta, Vincenzo, Greenwood, Celia, Grundberg, Elin, Johnson, Andrew D., Hui, Jennie, Lim, Ee M., McCarthy, Shane, Muddyman, Dawn, Panicker, Vijay, Perry, John R.B., Bell, Jordana T., Yuan, Wei, Relton, Caroline, Gaunt, Tom, Schlessinger, David, Abecasis, Goncalo, Cucca, Francesco, Surdulescu, Gabriela L., Woltersdorf, Wolfram, Zeggini, Eleftheria, Zheng, Hou-Feng, Toniolo, Daniela, Dayan, Colin M., Naitza, Silvia, Walsh, John P., Spector, Tim, Davey Smith, George, Durbin, Richard, Brent Richards, J., Sanna, Serena, Soranzo, Nicole, Timpson, Nicholas J., Wilson, Scott G., Turki, Saeed Al, Anderson, Carl, Anney, Richard, Antony, Dinu, Artigas, Maria Soler, Ayub, Muhammad, Balasubramaniam, Senduran, Barrett, Jeffrey C., Barroso, Inês, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Birney, Ewan, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick, Bounds, Rebecca, Boustred, Chris, Breen, Gerome, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Chen, Lu, Ciampi, Antonio, Cirak, Sebhattin, Clapham, Peter, Clement, Gail, Coates, Guy, Collier, David, Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Day-Williams, Aaron, Day, Ian N.M., Down, Thomas, Du, Yuanping, Dunham, Ian, Edkins, Sarah, Ellis, Peter, Evans, David, Faroogi, Sadaf, Fatemifar, Ghazaleh, Fitzpatrick, David R., Flicek, Paul, Flyod, James, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Geihs, Matthias, Geschwind, Daniel, Griffin, Heather, Grozeva, Detelina, Guo, Xueqin, Guo, Xiaosen, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey, Holmans, Peter, Howie, Bryan, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro, Jackson, David K., Jamshidi, Yalda, Jing, Tian, Joyce, Chris, Kaye, Jane, Keane, Thomas, Keogh, Julia, Kemp, John, Kennedy, Karen, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Lek, Monkol, Liang, Jieqin, Lin, Hong, Li, Rui, Li, Yingrui, Liu, Ryan, Lönnqvist, Jouko, Lopes, Margarida, Lotchkova, Valentina, MacArthur, Daniel, Marchini, Jonathan, Maslen, John, Massimo, Mangino, Mathieson, Iain, Marenne, Gaëlle, McGuffin, Peter, McIntosh, Andrew, McKechanie, Andrew G., McQuillin, Andrew, Metrustry, Sarah, Mitchison, Hannah, Moayyeri, Alireza, Morris, James, Muntoni, Francesco, Northstone, Kate, O'Donnovan, Michael, Onoufriadis, Alexandros, O'Rahilly, Stephen, Oualkacha, Karim, Owen, Michael J., Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Pietilainen, Olli, Plagnol, Vincent, Quaye, Lydia, Quai, Michael A., Raymond, Lucy, Rehnström, Karola, Richards, Brent, Ring, Susan, Ritchie, Graham R.S., Roberts, Nicola, Savage, David B., Scambler, Peter, Schiffels, Stephen, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Sharp, Sally I., Shin, So-Youn, Skuse, David, Small, Kerrin, Southam, Lorraine, Spasic-Boskovic, Olivera, Clair, David St, Stalker, Jim, Stevens, Elizabeth, Pourcian, Beate St, Sun, Jianping, Suvisaari, Jaana, Tachmazidou, Ionna, Tobin, Martin D., Valdes, Ana, Kogelenberg, Margriet Van, Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walters, James T.R., Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Wheeler, Elanor, Whyte, Tamieka, Williams, Hywel, Williamson, Kathleen A., Wilson, Crispian, Wong, Kim, Xu, ChangJiang, Yang, Jian, Zhang, Fend, and Zhang, Pingbo
- Abstract
Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10−9) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10−14). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10−9) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10−11). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.
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- 2015
240. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport
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Schmidts, Miriam, Hou, Yuqing, Cortés, Claudio R., Mans, Dorus A., Huber, Celine, Boldt, Karsten, Patel, Mitali, van Reeuwijk, Jeroen, Plaza, Jean-Marc, van Beersum, Sylvia E. C., Yap, Zhi Min, Letteboer, Stef J. F., Taylor, S. Paige, Herridge, Warren, Johnson, Colin A., Scambler, Peter J., Ueffing, Marius, Kayserili, Hulya, Krakow, Deborah, King, Stephen M., Beales, Philip L., Al-Gazali, Lihadh, Wicking, Carol, Cormier-Daire, Valerie, Roepman, Ronald, Mitchison, Hannah M., Witman, George B., Al-Turki, Saeed, Anderson, Carl, Anney, Richard, Antony, Dinu, Asimit, Jennifer, Ayub, Mohammad, Barrett, Jeff, Barroso, Inês, Bentham, Jamie, Bhattacharya, Shoumo, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick, Boustred, Chris, Breen, Gerome, Brion, Marie-Jo, Brown, Andrew, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Chen, Lu, Cirak, Sebhattin, Clapham, Peter, Clement, Gail, Coates, Guy, Collier, David, Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Daly, Allan, Danecek, Petr, Smith, George Davey, Day-Williams, Aaron, Day, Ian, Durbin, Richard, Edkins, Sarah, Ellis, Peter, Evans, David, Farooqi, I. Sadaf, Fatemifar, Ghazaleh, Fitzpatrick, David, Flicek, Paul, Floyd, Jamie, Foley, A. Reghan, Franklin, Chris, Futema, Marta, Gallagher, Louise, Gaunt, Tom, Geschwind, Daniel, Greenwood, Celia, Grozeva, Detelina, Guo, Xiaosen, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey, Holmans, Peter, Huang, Jie, Humphries, Steve E., Hurles, Matt, Hysi, Pirro, Jackson, David, Jamshidi, Yalda, Jewell, David, Chris, Joyce, Kaye, Jane, Keane, Thomas, Kemp, John, Kennedy, Karen, Kent, Alastair, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lee, Irene, Li, Rui, Li, Yingrui, Ryan, Liu, Lönnqvist, Jouko, Lopes, Margarida, MacArthur, Daniel G., Massimo, Mangino, Marchini, Jonathan, Maslen, John, McCarthy, Shane, McGuffin, Peter, McIntosh, Andrew, McKechanie, Andrew, McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Min, Josine, Moayyeri, Alireza, Morris, James, Muddyman, Dawn, Muntoni, Francesco, Northstone, Kate, O’Donovan, Michael, O’Rahilly, Stephen, Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy, Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Perry, John, Pietilainen, Olli, Plagnol, Vincent, Quail, Michael A., Quaye, Lydia, Raymond, Lucy, Rehnström, Karola, Brent Richards, J., Ring, Sue, Ritchie, Graham R S, Savage, David B., Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Shihab, Hashem, Shin, So-Youn, Skuse, David, Small, Kerrin, Smee, Carol, Soler, Artigas María, Soranzo, Nicole, Southam, Lorraine, Spector, Tim, St Pourcain, Beate, St. Clair, David, Stalker, Jim, Surdulescu, Gabriela, Suvisaari, Jaana, Tachmazidou, Ioanna, Tian, Jing, Timpson, Nic, Tobin, Martin, Valdes, Ana, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Wain, Louise, Walter, Klaudia, Wang, Jun, Ward, Kirsten, Wheeler, Ellie, Whittall, Ros, Williams, Hywel, Williamson, Kathy, Wilson, Scott G., Wong, Kim, Whyte, Tamieka, ChangJiang, Xu, Zeggini, Eleftheria, Zhang, Feng, Zheng, Hou-Feng, Schmidts, Miriam, Hou, Yuqing, Cortés, Claudio R., Mans, Dorus A., Huber, Celine, Boldt, Karsten, Patel, Mitali, van Reeuwijk, Jeroen, Plaza, Jean-Marc, van Beersum, Sylvia E. C., Yap, Zhi Min, Letteboer, Stef J. F., Taylor, S. Paige, Herridge, Warren, Johnson, Colin A., Scambler, Peter J., Ueffing, Marius, Kayserili, Hulya, Krakow, Deborah, King, Stephen M., Beales, Philip L., Al-Gazali, Lihadh, Wicking, Carol, Cormier-Daire, Valerie, Roepman, Ronald, Mitchison, Hannah M., Witman, George B., Al-Turki, Saeed, Anderson, Carl, Anney, Richard, Antony, Dinu, Asimit, Jennifer, Ayub, Mohammad, Barrett, Jeff, Barroso, Inês, Bentham, Jamie, Bhattacharya, Shoumo, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick, Boustred, Chris, Breen, Gerome, Brion, Marie-Jo, Brown, Andrew, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Chen, Lu, Cirak, Sebhattin, Clapham, Peter, Clement, Gail, Coates, Guy, Collier, David, Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Daly, Allan, Danecek, Petr, Smith, George Davey, Day-Williams, Aaron, Day, Ian, Durbin, Richard, Edkins, Sarah, Ellis, Peter, Evans, David, Farooqi, I. Sadaf, Fatemifar, Ghazaleh, Fitzpatrick, David, Flicek, Paul, Floyd, Jamie, Foley, A. Reghan, Franklin, Chris, Futema, Marta, Gallagher, Louise, Gaunt, Tom, Geschwind, Daniel, Greenwood, Celia, Grozeva, Detelina, Guo, Xiaosen, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey, Holmans, Peter, Huang, Jie, Humphries, Steve E., Hurles, Matt, Hysi, Pirro, Jackson, David, Jamshidi, Yalda, Jewell, David, Chris, Joyce, Kaye, Jane, Keane, Thomas, Kemp, John, Kennedy, Karen, Kent, Alastair, Kolb-Kokocinski, Anja, Lachance, Genevieve, Langford, Cordelia, Lee, Irene, Li, Rui, Li, Yingrui, Ryan, Liu, Lönnqvist, Jouko, Lopes, Margarida, MacArthur, Daniel G., Massimo, Mangino, Marchini, Jonathan, Maslen, John, McCarthy, Shane, McGuffin, Peter, McIntosh, Andrew, McKechanie, Andrew, McQuillin, Andrew, Memari, Yasin, Metrustry, Sarah, Min, Josine, Moayyeri, Alireza, Morris, James, Muddyman, Dawn, Muntoni, Francesco, Northstone, Kate, O’Donovan, Michael, O’Rahilly, Stephen, Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael, Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy, Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Perry, John, Pietilainen, Olli, Plagnol, Vincent, Quail, Michael A., Quaye, Lydia, Raymond, Lucy, Rehnström, Karola, Brent Richards, J., Ring, Sue, Ritchie, Graham R S, Savage, David B., Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Shihab, Hashem, Shin, So-Youn, Skuse, David, Small, Kerrin, Smee, Carol, Soler, Artigas María, Soranzo, Nicole, Southam, Lorraine, Spector, Tim, St Pourcain, Beate, St. Clair, David, Stalker, Jim, Surdulescu, Gabriela, Suvisaari, Jaana, Tachmazidou, Ioanna, Tian, Jing, Timpson, Nic, Tobin, Martin, Valdes, Ana, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Wain, Louise, Walter, Klaudia, Wang, Jun, Ward, Kirsten, Wheeler, Ellie, Whittall, Ros, Williams, Hywel, Williamson, Kathy, Wilson, Scott G., Wong, Kim, Whyte, Tamieka, ChangJiang, Xu, Zeggini, Eleftheria, Zhang, Feng, and Zheng, Hou-Feng
- Abstract
The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.
- Published
- 2015
241. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer.
- Author
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Westcott, Peter MK, Westcott, Peter MK, Halliwill, Kyle D, To, Minh D, Rashid, Mamunur, Rust, Alistair G, Keane, Thomas M, Delrosario, Reyno, Jen, Kuang-Yu, Gurley, Kay E, Kemp, Christopher J, Fredlund, Erik, Quigley, David A, Adams, David J, Balmain, Allan, Westcott, Peter MK, Westcott, Peter MK, Halliwill, Kyle D, To, Minh D, Rashid, Mamunur, Rust, Alistair G, Keane, Thomas M, Delrosario, Reyno, Jen, Kuang-Yu, Gurley, Kay E, Kemp, Christopher J, Fredlund, Erik, Quigley, David A, Adams, David J, and Balmain, Allan
- Abstract
Next-generation sequencing of human tumours has refined our understanding of the mutational processes operative in cancer initiation and progression, yet major questions remain regarding the factors that induce driver mutations and the processes that shape mutation selection during tumorigenesis. Here we performed whole-exome sequencing on adenomas from three mouse models of non-small-cell lung cancer, which were induced either by exposure to carcinogens (methyl-nitrosourea (MNU) and urethane) or by genetic activation of Kras (Kras(LA2)). Although the MNU-induced tumours carried exactly the same initiating mutation in Kras as seen in the Kras(LA2) model (G12D), MNU tumours had an average of 192 non-synonymous, somatic single-nucleotide variants, compared with only six in tumours from the Kras(LA2) model. By contrast, the Kras(LA2) tumours exhibited a significantly higher level of aneuploidy and copy number alterations compared with the carcinogen-induced tumours, suggesting that carcinogen-induced and genetically engineered models lead to tumour development through different routes. The wild-type allele of Kras has been shown to act as a tumour suppressor in mouse models of non-small-cell lung cancer. We demonstrate that urethane-induced tumours from wild-type mice carry mostly (94%) Kras Q61R mutations, whereas those from Kras heterozygous animals carry mostly (92%) Kras Q61L mutations, indicating a major role for germline Kras status in mutation selection during initiation. The exome-wide mutation spectra in carcinogen-induced tumours overwhelmingly display signatures of the initiating carcinogen, while adenocarcinomas acquire additional C > T mutations at CpG sites. These data provide a basis for understanding results from human tumour genome sequencing, which has identified two broad categories of tumours based on the relative frequency of single-nucleotide variations and copy number alterations, and underline the importance of carcinogen models for understan
- Published
- 2015
242. The UK10K project identifies rare variants in health and disease
- Author
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Walter, Klaudia, Min, Josine L., Huang, Jie, Crooks, Lucy, Memari, Yasin, McCarthy, Shane, Perry, John R. B., Xu, ChangJiang, Futema, Marta, Lawson, Daniel, Iotchkova, Valentina, Schiffels, Stephan, Hendricks, Audrey E., Danecek, Petr, Li, Rui, Floyd, James, Wain, Louise V., Barroso, Ines, Humphries, Steve E., Hurles, Matthew E., Zeggini, Eleftheria, Barrett, Jeffrey C., Plagnol, Vincent, Richards, J. Brent, Greenwood, Celia M. T., Timpson, Nicholas J., Durbin, Richard, Soranzo, Nicole, Bala, Senduran, Clapham, Peter, Coates, Guy, Cox, Tony, Daly, Allan, Du, Yuanping, Edkins, Sarah, Ellis, Peter, Flicek, Paul, Guo, Xiaosen, Guo, Xueqin, Huang, Liren, Jackson, David K., Joyce, Chris, Keane, Thomas, Kolb-Kokocinski, Anja, Langford, Cordelia, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Maslen, John, Muddyman, Dawn, Quail, Michael A., Stalker, Jim, Sun, Jianping, Tian, Jing, Wang, Guangbiao, Wang, Jun, Wang, Yu, Wong, Kim, Zhang, Pingbo, Birney, Ewan, Boustred, Chris, Chen, Lu, Clement, Gail, Cocca, Massimiliano, Smith, George Davey, Day, Ian N. M., Day-Williams, Aaron, Down, Thomas, Dunham, Ian, Evans, David M., Gaunt, Tom R., Geihs, Matthias, Hart, Deborah, Howie, Bryan, Hubbard, Tim, Hysi, Pirro, Jamshidi, Yalda, Karczewski, Konrad J., Kemp, John P., Lachance, Genevieve, Lek, Monkol, Lopes, Margarida, MacArthur, Daniel G., Marchini, Jonathan, Mangino, Massimo, Mathieson, Iain, Metrustry, Sarah, Moayyeri, Alireza, Northstone, Kate, Panoutsopoulou, Kalliope, Paternoster, Lavinia, Quaye, Lydia, Ring, Susan, Ritchie, Graham R. S., Shihab, Hashem A., Shin, So-Youn, Small, Kerrin S., Artigas, Maria Soler, Southam, Lorraine, Spector, Timothy D., St Pourcain, Beate, Surdulescu, Gabriela, Tachmazidou, Ioanna, Tobin, Martin D., Valdes, Ana M., Visscher, Peter M., Ward, Kirsten, Wilson, Scott G., Yang, Jian, Zhang, Feng, Zheng, Hou-Feng, Anney, Richard, Ayub, Muhammad, Blackwood, Douglas, Bolton, Patrick F., Breen, Gerome, Collier, David A., Craddock, Nick, Curran, Sarah, Curtis, David, Gallagher, Louise, Geschwind, Daniel, Gurling, Hugh, Holmans, Peter, Lee, Irene, Lonnqvist, Jouko, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Morris, James, O'Donovan, Michael C., Owen, Michael J., Palotie, Aarno, Parr, Jeremy R., Paunio, Tiina, Pietilainen, Olli, Rehnstrom, Karola, Sharp, Sally I., Skuse, David, St Clair, David, Suvisaari, Jaana, Walters, James T. R., Williams, Hywel J., Bochukova, Elena, Bounds, Rebecca, Dominiczak, Anna, Farooqi, I. Sadaf, Keogh, Julia, Marenne, Gae Lle, Morris, Andrew, O'Rahilly, Stephen, Porteous, David J., Smith, Blair H., Wheeler, Eleanor, Al Turki, Saeed, Anderson, Carl A., Antony, Dinu, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Fitzpatrick, David R., Foley, A. Reghan, Franklin, Christopher S., Grozeva, Detelina, Mitchison, Hannah M., Muntoni, Francesco, Onoufriadis, Alexandros, Parker, Victoria, Payne, Felicity, Raymond, F. Lucy, Roberts, Nicola, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Spasic-Boskovic, Olivera, Stevens, Elizabeth, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Williamson, Kathleen A., Wilson, Crispian, Whyte, Tamieka, Ciampi, Antonio, Oualkacha, Karim, Bobrow, Martin, Griffin, Heather, Kaye, Jane, Kennedy, Karen, Kent, Alastair, Smee, Carol, Charlton, Ruth, Ekong, Rosemary, Khawaja, Farrah, Lopes, Luis R., Migone, Nicola, Payne, Stewart J., Pollitt, Rebecca C., Povey, Sue, Ridout, Cheryl K., Robinson, Rachel L., Scott, Richard H., Shaw, Adam, Syrris, Petros, Taylor, Rohan, Vandersteen, Anthony M., Amuzu, Antoinette, Casas, Juan Pablo, Chambers, John C., Dedoussis, George, Gambaro, Giovanni, Gasparini, Paolo, Isaacs, Aaron, Johnson, Jon, Kleber, Marcus E., Kooner, Jaspal S., Langenberg, Claudia, Luan, Jian'an, Malerba, Giovanni, Maerz, Winfried, Matchan, Angela, Morris, Richard, Nordestgaard, Borge G., Benn, Marianne, Scott, Robert A., Toniolo, Daniela, Traglia, Michela, Tybjaerg-Hansen, Anne, van Duijn, Cornelia M., van Leeuwen, Elisabeth M., Varbo, Anette, Whincup, Peter, Zaza, Gianluigi, Zhang, Weihua, Walter, Klaudia, Min, Josine L., Huang, Jie, Crooks, Lucy, Memari, Yasin, McCarthy, Shane, Perry, John R. B., Xu, ChangJiang, Futema, Marta, Lawson, Daniel, Iotchkova, Valentina, Schiffels, Stephan, Hendricks, Audrey E., Danecek, Petr, Li, Rui, Floyd, James, Wain, Louise V., Barroso, Ines, Humphries, Steve E., Hurles, Matthew E., Zeggini, Eleftheria, Barrett, Jeffrey C., Plagnol, Vincent, Richards, J. Brent, Greenwood, Celia M. T., Timpson, Nicholas J., Durbin, Richard, Soranzo, Nicole, Bala, Senduran, Clapham, Peter, Coates, Guy, Cox, Tony, Daly, Allan, Du, Yuanping, Edkins, Sarah, Ellis, Peter, Flicek, Paul, Guo, Xiaosen, Guo, Xueqin, Huang, Liren, Jackson, David K., Joyce, Chris, Keane, Thomas, Kolb-Kokocinski, Anja, Langford, Cordelia, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Maslen, John, Muddyman, Dawn, Quail, Michael A., Stalker, Jim, Sun, Jianping, Tian, Jing, Wang, Guangbiao, Wang, Jun, Wang, Yu, Wong, Kim, Zhang, Pingbo, Birney, Ewan, Boustred, Chris, Chen, Lu, Clement, Gail, Cocca, Massimiliano, Smith, George Davey, Day, Ian N. M., Day-Williams, Aaron, Down, Thomas, Dunham, Ian, Evans, David M., Gaunt, Tom R., Geihs, Matthias, Hart, Deborah, Howie, Bryan, Hubbard, Tim, Hysi, Pirro, Jamshidi, Yalda, Karczewski, Konrad J., Kemp, John P., Lachance, Genevieve, Lek, Monkol, Lopes, Margarida, MacArthur, Daniel G., Marchini, Jonathan, Mangino, Massimo, Mathieson, Iain, Metrustry, Sarah, Moayyeri, Alireza, Northstone, Kate, Panoutsopoulou, Kalliope, Paternoster, Lavinia, Quaye, Lydia, Ring, Susan, Ritchie, Graham R. S., Shihab, Hashem A., Shin, So-Youn, Small, Kerrin S., Artigas, Maria Soler, Southam, Lorraine, Spector, Timothy D., St Pourcain, Beate, Surdulescu, Gabriela, Tachmazidou, Ioanna, Tobin, Martin D., Valdes, Ana M., Visscher, Peter M., Ward, Kirsten, Wilson, Scott G., Yang, Jian, Zhang, Feng, Zheng, Hou-Feng, Anney, Richard, Ayub, Muhammad, Blackwood, Douglas, Bolton, Patrick F., Breen, Gerome, Collier, David A., Craddock, Nick, Curran, Sarah, Curtis, David, Gallagher, Louise, Geschwind, Daniel, Gurling, Hugh, Holmans, Peter, Lee, Irene, Lonnqvist, Jouko, McGuffin, Peter, McIntosh, Andrew M., McKechanie, Andrew G., McQuillin, Andrew, Morris, James, O'Donovan, Michael C., Owen, Michael J., Palotie, Aarno, Parr, Jeremy R., Paunio, Tiina, Pietilainen, Olli, Rehnstrom, Karola, Sharp, Sally I., Skuse, David, St Clair, David, Suvisaari, Jaana, Walters, James T. R., Williams, Hywel J., Bochukova, Elena, Bounds, Rebecca, Dominiczak, Anna, Farooqi, I. Sadaf, Keogh, Julia, Marenne, Gae Lle, Morris, Andrew, O'Rahilly, Stephen, Porteous, David J., Smith, Blair H., Wheeler, Eleanor, Al Turki, Saeed, Anderson, Carl A., Antony, Dinu, Beales, Phil, Bentham, Jamie, Bhattacharya, Shoumo, Calissano, Mattia, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Fitzpatrick, David R., Foley, A. Reghan, Franklin, Christopher S., Grozeva, Detelina, Mitchison, Hannah M., Muntoni, Francesco, Onoufriadis, Alexandros, Parker, Victoria, Payne, Felicity, Raymond, F. Lucy, Roberts, Nicola, Savage, David B., Scambler, Peter, Schmidts, Miriam, Schoenmakers, Nadia, Semple, Robert K., Serra, Eva, Spasic-Boskovic, Olivera, Stevens, Elizabeth, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Williamson, Kathleen A., Wilson, Crispian, Whyte, Tamieka, Ciampi, Antonio, Oualkacha, Karim, Bobrow, Martin, Griffin, Heather, Kaye, Jane, Kennedy, Karen, Kent, Alastair, Smee, Carol, Charlton, Ruth, Ekong, Rosemary, Khawaja, Farrah, Lopes, Luis R., Migone, Nicola, Payne, Stewart J., Pollitt, Rebecca C., Povey, Sue, Ridout, Cheryl K., Robinson, Rachel L., Scott, Richard H., Shaw, Adam, Syrris, Petros, Taylor, Rohan, Vandersteen, Anthony M., Amuzu, Antoinette, Casas, Juan Pablo, Chambers, John C., Dedoussis, George, Gambaro, Giovanni, Gasparini, Paolo, Isaacs, Aaron, Johnson, Jon, Kleber, Marcus E., Kooner, Jaspal S., Langenberg, Claudia, Luan, Jian'an, Malerba, Giovanni, Maerz, Winfried, Matchan, Angela, Morris, Richard, Nordestgaard, Borge G., Benn, Marianne, Scott, Robert A., Toniolo, Daniela, Traglia, Michela, Tybjaerg-Hansen, Anne, van Duijn, Cornelia M., van Leeuwen, Elisabeth M., Varbo, Anette, Whincup, Peter, Zaza, Gianluigi, and Zhang, Weihua
- Abstract
The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
- Published
- 2015
243. Interplay between Gliotoxin Resistance, Secretion, and the Methyl/ Methionine Cycle in Aspergillus fumigatus
- Author
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Owens, Rebecca A., O'Keeffe, Grainne, Smith, Elizabeth B., Dolan, Stephen K., Hammel, Stephen, Sheridan, Kevin J., Fitzpatrick, David A., Keane, Thomas M., Doyle, Sean, Owens, Rebecca A., O'Keeffe, Grainne, Smith, Elizabeth B., Dolan, Stephen K., Hammel, Stephen, Sheridan, Kevin J., Fitzpatrick, David A., Keane, Thomas M., and Doyle, Sean
- Abstract
Mechanistic studies on gliotoxin biosynthesis and self-protection in Aspergillus fumigatus, both of which require the gliotoxin oxidoreductase GliT, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. Here we show that an A. fumigatus ∆gliA strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (BmGT). This correlates with a significant increase in sensitivity to exogenous gliotoxin because gliotoxin trapped inside the cell leads to (i) activation of the gli cluster, as disabling gli cluster activation, via gliZ deletion, attenuates the sensitivity of an A. fumigatus ∆gliT strain to gliotoxin, thus implicating cluster activation as a factor in gliotoxin sensitivity, and (ii) increased methylation activity due to excess substrate (dithiol gliotoxin) for the gliotoxin bis-thiomethyltransferase GtmA. Intracellular dithiol gliotoxin is oxidized by GliT and subsequently effluxed by GliA. In the absence of GliA, gliotoxin persists in the cell and is converted to BmGT, with levels significantly higher than those in the wild type. Similarly, in the ∆gliT strain, gliotoxin oxidation is impeded, and methylation occurs unchecked, leading to significant S-adenosylmethionine (SAM) depletion and S-adenosylhomocysteine (SAH) overproduction. This in turn significantly contributes to the observed hypersensitivity of gliT-deficient A. fumigatus to gliotoxin. Our observations reveal a key role for GliT in preventing dysregulation of the methyl/methionine cycle to control intracellular SAM and SAH homeostasis during gliotoxin biosynthesis and exposure. Moreover, we reveal attenuated GliT abundance in the A. fumigatus ∆gliK strain, but not the ∆gliG strain, following exposure to gliotoxin, correlating with relative sensitivities. Overall, we illuminate new systems interactions that have evolved in gliotoxin-producing, compared to glio
- Published
- 2015
244. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel
- Author
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Huang, Jie, Howie, Bryan, Mccarthy, Shane, Memari, Yasin, Walter, Klaudia, Min, Josine L., Danecek, Petr, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hou-feng, Al Turki, Saeed, Amuzu, Antoinette, Anderson, Carl A., Anney, Richard, Antony, Dinu, Artigas, María Soler, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C., Barroso, Inês, Beales, Phil, Benn, Marianne, Bentham, Jamie, Bhattacharya, Shoumo, Birney, Ewan, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick F., Bounds, Rebecca, Boustred, Chris, Breen, Gerome, Calissano, Mattia, Carss, Keren, Pablo Casas, Juan, Chambers, John C., Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampi, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Cocca, Massimiliano, Collier, David A., Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Day, Ian N. M., Day-williams, Aaron, Dedoussis, George, Down, Thomas, Du, Yuanping, Van Duijn, Cornelia M., Dunham, Ian, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evans, David M., Farooqi, I. Sadaf, Fitzpatrick, David R., Flicek, Paul, Floyd, James, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gasparini, Paolo, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel, Greenwood, Celia, Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey E., Holmans, Peter, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro, Iotchkova, Valentina, Isaacs, Aaron, Jackson, David K., Jamshidi, Yalda, Johnson, Jon, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Keogh, Julia, Khawaja, Farrah, Kleber, Marcus E., Van Kogelenberg, Margriet, Kolb-kokocinski, Anja, Kooner, Jaspal S., Lachance, Genevieve, Langenberg, Claudia, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Van Leeuwen, Elisabeth M., Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, Luan, Jian'an, Macarthur, Daniel G., Mangino, Massimo, Marenne, Gaëlle, März, Winfried, Maslen, John, Matchan, Angela, Mathieson, Iain, Mcguffin, Peter, Mcintosh, Andrew M., Mckechanie, Andrew G., Mcquillin, Andrew, Metrustry, Sarah, Migone, Nicola, Mitchison, Hannah M., Moayyeri, Alireza, Morris, James, Morris, Richard, Muddyman, Dawn, Muntoni, Francesco, Nordestgaard, Børge, Northstone, Kate, O'donovan, Michael C., O'rahilly, Stephen, Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J., Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, Lucy, Rehnström, Karola, Ridout, Cheryl K., Ring, Susan, Ritchie, Graham R. S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Scott, Robert A., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So-youn, Skuse, David, Small, Kerrin S., Smee, Carol, Smith, George Davey, Southam, Lorraine, Spasic-boskovic, Olivera, Spector, Timothy D., St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela, Suvisaari, Jaana, Syrris, Petros, Tachmazidou, Ioanna, Taylor, Rohan, Tian, Jing, Tobin, Martin D., Toniolo, Daniela, Traglia, Michela, Tybjærg-Hansen, Anne, Valdes, Ana M., Vandersteen, Anthony M., Varbo, Anette, Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walters, James T. R., Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Wheeler, Eleanor, Whincup, Peter, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zaza, Gianluigi, Zeggini, Eleftheria, Zhang, Feng, Zhang, Pingbo, Zhang, Weihua, Gambaro, Giovanni, Richards, J. Brent, Durbin, Richard, Timpson, Nicholas J., Marchini, Jonathan, Soranzo, Nicole, Huang, Jie, Howie, Bryan, Mccarthy, Shane, Memari, Yasin, Walter, Klaudia, Min, Josine L., Danecek, Petr, Malerba, Giovanni, Trabetti, Elisabetta, Zheng, Hou-feng, Al Turki, Saeed, Amuzu, Antoinette, Anderson, Carl A., Anney, Richard, Antony, Dinu, Artigas, María Soler, Ayub, Muhammad, Bala, Senduran, Barrett, Jeffrey C., Barroso, Inês, Beales, Phil, Benn, Marianne, Bentham, Jamie, Bhattacharya, Shoumo, Birney, Ewan, Blackwood, Douglas, Bobrow, Martin, Bochukova, Elena, Bolton, Patrick F., Bounds, Rebecca, Boustred, Chris, Breen, Gerome, Calissano, Mattia, Carss, Keren, Pablo Casas, Juan, Chambers, John C., Charlton, Ruth, Chatterjee, Krishna, Chen, Lu, Ciampi, Antonio, Cirak, Sebahattin, Clapham, Peter, Clement, Gail, Coates, Guy, Cocca, Massimiliano, Collier, David A., Cosgrove, Catherine, Cox, Tony, Craddock, Nick, Crooks, Lucy, Curran, Sarah, Curtis, David, Daly, Allan, Day, Ian N. M., Day-williams, Aaron, Dedoussis, George, Down, Thomas, Du, Yuanping, Van Duijn, Cornelia M., Dunham, Ian, Edkins, Sarah, Ekong, Rosemary, Ellis, Peter, Evans, David M., Farooqi, I. Sadaf, Fitzpatrick, David R., Flicek, Paul, Floyd, James, Foley, A. Reghan, Franklin, Christopher S., Futema, Marta, Gallagher, Louise, Gasparini, Paolo, Gaunt, Tom R., Geihs, Matthias, Geschwind, Daniel, Greenwood, Celia, Griffin, Heather, Grozeva, Detelina, Guo, Xiaosen, Guo, Xueqin, Gurling, Hugh, Hart, Deborah, Hendricks, Audrey E., Holmans, Peter, Huang, Liren, Hubbard, Tim, Humphries, Steve E., Hurles, Matthew E., Hysi, Pirro, Iotchkova, Valentina, Isaacs, Aaron, Jackson, David K., Jamshidi, Yalda, Johnson, Jon, Joyce, Chris, Karczewski, Konrad J., Kaye, Jane, Keane, Thomas, Kemp, John P., Kennedy, Karen, Kent, Alastair, Keogh, Julia, Khawaja, Farrah, Kleber, Marcus E., Van Kogelenberg, Margriet, Kolb-kokocinski, Anja, Kooner, Jaspal S., Lachance, Genevieve, Langenberg, Claudia, Langford, Cordelia, Lawson, Daniel, Lee, Irene, Van Leeuwen, Elisabeth M., Lek, Monkol, Li, Rui, Li, Yingrui, Liang, Jieqin, Lin, Hong, Liu, Ryan, Lönnqvist, Jouko, Lopes, Luis R., Lopes, Margarida, Luan, Jian'an, Macarthur, Daniel G., Mangino, Massimo, Marenne, Gaëlle, März, Winfried, Maslen, John, Matchan, Angela, Mathieson, Iain, Mcguffin, Peter, Mcintosh, Andrew M., Mckechanie, Andrew G., Mcquillin, Andrew, Metrustry, Sarah, Migone, Nicola, Mitchison, Hannah M., Moayyeri, Alireza, Morris, James, Morris, Richard, Muddyman, Dawn, Muntoni, Francesco, Nordestgaard, Børge, Northstone, Kate, O'donovan, Michael C., O'rahilly, Stephen, Onoufriadis, Alexandros, Oualkacha, Karim, Owen, Michael J., Palotie, Aarno, Panoutsopoulou, Kalliope, Parker, Victoria, Parr, Jeremy R., Paternoster, Lavinia, Paunio, Tiina, Payne, Felicity, Payne, Stewart J., Perry, John R. B., Pietilainen, Olli, Plagnol, Vincent, Pollitt, Rebecca C., Povey, Sue, Quail, Michael A., Quaye, Lydia, Raymond, Lucy, Rehnström, Karola, Ridout, Cheryl K., Ring, Susan, Ritchie, Graham R. S., Roberts, Nicola, Robinson, Rachel L., Savage, David B., Scambler, Peter, Schiffels, Stephan, Schmidts, Miriam, Schoenmakers, Nadia, Scott, Richard H., Scott, Robert A., Semple, Robert K., Serra, Eva, Sharp, Sally I., Shaw, Adam, Shihab, Hashem A., Shin, So-youn, Skuse, David, Small, Kerrin S., Smee, Carol, Smith, George Davey, Southam, Lorraine, Spasic-boskovic, Olivera, Spector, Timothy D., St Clair, David, St Pourcain, Beate, Stalker, Jim, Stevens, Elizabeth, Sun, Jianping, Surdulescu, Gabriela, Suvisaari, Jaana, Syrris, Petros, Tachmazidou, Ioanna, Taylor, Rohan, Tian, Jing, Tobin, Martin D., Toniolo, Daniela, Traglia, Michela, Tybjærg-Hansen, Anne, Valdes, Ana M., Vandersteen, Anthony M., Varbo, Anette, Vijayarangakannan, Parthiban, Visscher, Peter M., Wain, Louise V., Walters, James T. R., Wang, Guangbiao, Wang, Jun, Wang, Yu, Ward, Kirsten, Wheeler, Eleanor, Whincup, Peter, Whyte, Tamieka, Williams, Hywel J., Williamson, Kathleen A., Wilson, Crispian, Wilson, Scott G., Wong, Kim, Xu, Changjiang, Yang, Jian, Zaza, Gianluigi, Zeggini, Eleftheria, Zhang, Feng, Zhang, Pingbo, Zhang, Weihua, Gambaro, Giovanni, Richards, J. Brent, Durbin, Richard, Timpson, Nicholas J., Marchini, Jonathan, and Soranzo, Nicole
- Published
- 2015
245. The genomic and phenotypic diversity of Schizosaccharomyces pombe
- Author
-
Jeffares, Daniel C., Rallis, Charalampos, Rieux, Adrien, Speed, Doug, Převorovský, Martin, Mourier, Tobias, Marsellach, Francesc X., Iqbal, Zamin, Lau, Winston, Cheng, Tammy M. K., Pracana, Rodrigo, Mülleder, Michael, Lawson, Jonathan L. D., Chessel, Anatole, Bala, Sendu, Hellenthal, Garrett, O'Fallon, Brendan, Keane, Thomas, Simpson, Jared T., Bischof, Leanne, Tomiczek, Bartlomiej, Bitton, Danny A., Sideri, Theodora, Codlin, Sandra, Hellberg, Josephine E. E. U., van Trigt, Laurent, Jeffery, Linda, Li, Juan-Juan, Atkinson, Sophie, Thodberg, Malte, Febrer, Melanie, McLay, Kirsten, Drou, Nizar, Brown, William, Hayles, Jacqueline, Salas, Rafael E. Carazo, Ralser, Markus, Maniatis, Nikolas, Balding, David J., Balloux, Francois, Durbin, Richard, Bähler, Jürg, Jeffares, Daniel C., Rallis, Charalampos, Rieux, Adrien, Speed, Doug, Převorovský, Martin, Mourier, Tobias, Marsellach, Francesc X., Iqbal, Zamin, Lau, Winston, Cheng, Tammy M. K., Pracana, Rodrigo, Mülleder, Michael, Lawson, Jonathan L. D., Chessel, Anatole, Bala, Sendu, Hellenthal, Garrett, O'Fallon, Brendan, Keane, Thomas, Simpson, Jared T., Bischof, Leanne, Tomiczek, Bartlomiej, Bitton, Danny A., Sideri, Theodora, Codlin, Sandra, Hellberg, Josephine E. E. U., van Trigt, Laurent, Jeffery, Linda, Li, Juan-Juan, Atkinson, Sophie, Thodberg, Malte, Febrer, Melanie, McLay, Kirsten, Drou, Nizar, Brown, William, Hayles, Jacqueline, Salas, Rafael E. Carazo, Ralser, Markus, Maniatis, Nikolas, Balding, David J., Balloux, Francois, Durbin, Richard, and Bähler, Jürg
- Published
- 2015
246. Aloha, marriage? Constitutional and choice of law arguments for recognition of same-sex marriages
- Author
-
Keane, Thomas M.
- Subjects
Same-sex marriage -- Laws, regulations and rules ,Full faith and credit (Law) -- Laws, regulations and rules ,Conflict of laws -- Marriage ,United States Constitution - Published
- 1995
247. Primary radiation therapy in the treatment of anal canal carcinoma
- Author
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Cummings, Bernard J., Thomas, Gillian M., Keane, Thomas J., Harwood, Andrew R., and Rider, Walter D.
- Published
- 1982
- Full Text
- View/download PDF
248. Cellular dysmaturity as a prognostic index in acute myeloid leukaemia
- Author
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O’Connell, Liam G., Gorman, Angela, Keane, Thomas J., and Fennelly, James J.
- Published
- 1976
- Full Text
- View/download PDF
249. Radical external beam radiation therapy for adenocarcinoma of the rectum
- Author
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Cummings, Bernard J., Rider, Walter D., Harwood, Andrew R., Keane, Thomas J., and Thomas, Gillian M.
- Published
- 1983
- Full Text
- View/download PDF
250. The European Nucleotide Archive in 2017.
- Author
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Silvester, Nicole, Alako, Blaise, Amid, Clara, Cerdeño-Tarrága, Ana, Clarke, Laura, Cleland, Iain, Harrison, Peter W, Jayathilaka, Suran, Kay, Simon, and Keane, Thomas
- Published
- 2018
- Full Text
- View/download PDF
Catalog
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