Search

Your search keyword '"Louzada, Sandra"' showing total 158 results
Start Over Author "Louzada, Sandra"
158 results on '"Louzada, Sandra"'

7. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes

Author

Mueller, Sebastian, Engleitner, Thomas, Maresch, Roman, Zukowska, Magdalena, Lange, Sebastian, Kaltenbacher, Thorsten, Konukiewitz, Bjrn, llinger, Rupert, Zwiebel, Maximilian, Strong, Alex, Yen, Hsi-Yu, Banerjee, Ruby, Louzada, Sandra, Fu, Beiyuan, Seidler, Barbara, Gtzfried, Juliana, Schuck, Kathleen, Hassan, Zonera, Arbeiter, Andreas, Schnhuber, Nina, Klein, Sabine, Veltkamp, Christian, Friedrich, Mathias, Rad, Lena, Barenboim, Maxim, Ziegenhain, Christoph, Hess, Julia, Dovey, Oliver M., Eser, Stefan, Parekh, Swati, Constantino-Casas, Fernando, de la Rosa, Jorge, Sierra, Marta I., Fraga, Mario, Mayerle, Julia, Klppel, Gnter, Cadianos, Juan, Liu, Pentao, Vassiliou, George, Weichert, Wilko, Steiger, Katja, Enard, Wolfgang, Schmid, Roland M., Yang, Fengtang, Unger, Kristian, Schneider, Gnter, Varela, Ignacio, Bradley, Allan, Saur, Dieter, and Rad, Roland

Subjects
Phenotypes -- Research, Cell culture -- Research, Pancreatic cancer -- Genetic aspects -- Physiological aspects, Biological research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest Kras[sup.MUT] levels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous Kras[sup.MUT] in driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgf-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer., Author(s): Sebastian Mueller [1, 2]; Thomas Engleitner [1, 2, 3]; Roman Maresch [1, 2, 3]; Magdalena Zukowska [1, 2]; Sebastian Lange [1, 2]; Thorsten Kaltenbacher [1, 2, 3]; Bjrn Konukiewitz [...]

Published
2018
Full Text
View/download PDF

8. A new patient‐derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α‐dystroglycan

Author

Kim, Jihee, Lana, Beatrice, Torelli, Silvia, Ryan, David, Catapano, Francesco, Ala, Pierpaolo, Luft, Christin, Stevens, Elizabeth, Konstantinidis, Evangelos, Louzada, Sandra, Fu, Beiyuan, Paredes‐Redondo, Amaia, Chan, AW Edith, Yang, Fengtang, Stemple, Derek L, Liu, Pentao, Ketteler, Robin, Selwood, David L, Muntoni, Francesco, and Lin, Yung‐Yao

Published
2019
Full Text
View/download PDF

10. ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma

Author

Rashid, Mamunur, van der Horst, Michiel, Mentzel, Thomas, Butera, Francesca, Ferreira, Ingrid, Pance, Alena, Rütten, Arno, Luzar, Bostjan, Marusic, Zlatko, de Saint Aubain, Nicolas, Ko, Jennifer S., Billings, Steven D., Chen, Sofia, Abi Daoud, Marie, Hewinson, James, Louzada, Sandra, Harms, Paul W., Cerretelli, Guia, Robles-Espinoza, Carla Daniela, Patel, Rajiv M., van der Weyden, Louise, Bakal, Chris, Hornick, Jason L., Arends, Mark J., Brenn, Thomas, and Adams, David J.

Published
2019
Full Text
View/download PDF

15. Additional file 1 of Human Satellite 1A analysis provides evidence of pericentromeric transcription

Author

Lopes, Mariana, Louzada, Sandra, Ferreira, Daniela, Veríssimo, Gabriela, Eleutério, Daniel, Gama-Carvalho, Margarida, and Chaves, Raquel

Abstract

Additional file 1: Supplementary Table S1. Primer sequences for HSat1A isolation. The first set of primers was also used for qPCR and RT-qPCR reactions. Supplementary Table S2. Quantification of repetitive sequences HSat1A and HSat1A_clone6 based on NA12878 sequencing data. *Genomic abundance is an estimation based on the total number of bp on all the reads, 15,666,888 bp. Supplementary Table S3. Distance matrix (% identity) of the alignment between representative HSat1A clones, L01057.1 (extracted region), and CP068265.2 (extracted region). Distances were calculated using Geneious alignment (version 9.1.8, Biomatters). Supplementary Table S4. Analysis of the average intensity of active signal objects (all slices) in RNA-FISH control and RNA-FISH with RNase A treatment, performed in ‘Counting and Tracking, AutoQuant X3 (Media Cybernetics). Data presented as mean ± SD for the analysis of 20 cells. Supplementary Table S5. Sequencing run statistics for 3’RACE-Seq (Whole Genome Library Preparation, Illumina MiSeq plataform, NGS Sequencing service STAB VIDA). Supplementary Table S6. Cell lines description table, specifying tissue and type (tumoral and non-tumoral). Supplementary Table S7. Standard curves parameters and PCR programs for both reactions (DNA copy number qPCR and RNA RT-qPCR). Supplementary Figure S1. Visual representation of the obtained BLAST hits from Supplementary Table S3 (query: HSat1A clone; Database: nt). A total of 8167 hits is distributed for 47 sequences, 38 of which (5000 hits) belong to unlocalized sequences from a sequencing project for the “Construction and Integration of Three De Novo Japanese Human Genome Assemblies toward a Population-Specific Reference” (BioSample: SAMD00243993; Bioproject: PRJDB10452) [119, 120]. CP068257.2, CP068256.2, and CP068263.2 represent accessions from CHM13 T2T v2.0 (GCA_009914755.4) human assembly. Supplementary Figure S2. Statistical analysis (one-way ANOVA with Tukey ‘s multiple comparisons test) of monomer copy number (data from supplementary Table S6). *P≤0.05, **P≤0.01, ***P≤0.001, ****P≤0.0001, ns - not statistically significant. Supplementary Figure S3. HSat1A FISH mapping (red) in chromosome 1 (blue). Signal hybridization in chromosome 1 is visible in GM12878, MCF10A, HDFn, and GM03417 (non-tumoral cell lines). Supplementary Figure S4. Original uncropped gel for Figure 4A; the box indicates where the gel was cropped. Supplementary Figure S5. Comparison between the HSat1A monomer sequence and a selection of motifs sequences in each cluster group through a merged alignment. Supplementary Figure S6. Workflow for the analysis of HSat1A RACE-Seq.

Published
2023
Full Text
View/download PDF

20. Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice

Author

Maresch, Roman, Mueller, Sebastian, Veltkamp, Christian, Öllinger, Rupert, Friedrich, Mathias, Heid, Irina, Steiger, Katja, Weber, Julia, Engleitner, Thomas, Barenboim, Maxim, Klein, Sabine, Louzada, Sandra, Banerjee, Ruby, Strong, Alexander, Stauber, Teresa, Gross, Nina, Geumann, Ulf, Lange, Sebastian, Ringelhan, Marc, Varela, Ignacio, Unger, Kristian, Yang, Fengtang, Schmid, Roland M., Vassiliou, George S., Braren, Rickmer, Schneider, Günter, Heikenwalder, Mathias, Bradley, Allan, Saur, Dieter, and Rad, Roland

Published
2016
Full Text
View/download PDF

21. A global reference for human genetic variation

Author

Altshuler, David M., (Co-Chair), Durbin, Richard M., (Co-Chair, Principal Investigator), Donnelly, Peter, Green, Eric D., Nickerson, Deborah A., Boerwinkle, Eric, Doddapaneni, Harsha, Han, Yi, Korchina, Viktoriya, Kovar, Christie, Lee, Sandra, Muzny, Donna, Reid, Jeffrey G., Zhu, Yiming, Wang, Jun, (Principal Investigator), Chang, Yuqi, Feng, Qiang, Fang, Xiaodong, Guo, Xiaosen, Jian, Min, Jiang, Hui, Jin, Xin, Lan, Tianming, Li, Guoqing, Li, Jingxiang, Li, Yingrui, Liu, Shengmao, Liu, Xiao, Lu, Yao, Ma, Xuedi, Tang, Meifang, Wang, Bo, Wang, Guangbiao, Wu, Honglong, Wu, Renhua, Xu, Xun, Yin, Ye, Zhang, Dandan, Zhang, Wenwei, Zhao, Jiao, Zhao, Meiru, Zheng, Xiaole, Lander, Eric S., (Principal Investigator), Gabriel, Stacey B., (Co-Chair), Gupta, Namrata, Gharani, Neda, Toji, Lorraine H., Gerry, Norman P., Resch, Alissa M., Barker, Jonathan, Gil, Laurent, Hunt, Sarah E., Kelman, Gavin, Kulesha, Eugene, Leinonen, Rasko, McLaren, William M., Radhakrishnan, Rajesh, Roa, Asier, Smirnov, Dmitriy, Smith, Richard E., Streeter, Ian, Thormann, Anja, Toneva, Iliana, Vaughan, Brendan, Zheng-Bradley, Xiangqun, Bentley, David R., (Principal Investigator), Grocock, Russell, Humphray, Sean, James, Terena, Kingsbury, Zoya, Lehrach, Hans, (Principal Investigator), Sudbrak, Ralf, (Project Leader), Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Borodina, Tatiana A., Lienhard, Matthias, Mertes, Florian, Sultan, Marc, Timmermann, Bernd, Yaspo, Marie-Laure, Mardis, Elaine R., (Co-Principal Investigator) (Co-Chair), Wilson, Richard K., (Co-Principal Investigator), Fulton, Lucinda, Fulton, Robert, Ananiev, Victor, Belaia, Zinaida, Beloslyudtsev, Dimitriy, Bouk, Nathan, Chen, Chao, Church, Deanna, Cohen, Robert, Cook, Charles, Garner, John, Hefferon, Timothy, Kimelman, Mikhail, Liu, Chunlei, Lopez, John, Meric, Peter, O’Sullivan, Chris, Ostapchuk, Yuri, Phan, Lon, Ponomarov, Sergiy, Schneider, Valerie, Shekhtman, Eugene, Sirotkin, Karl, Slotta, Douglas, Zhang, Hua, Balasubramaniam, Senduran, Burton, John, Danecek, Petr, Keane, Thomas M., Kolb-Kokocinski, Anja, McCarthy, Shane, Stalker, James, Quail, Michael, Schmidt, Jeanette P., (Principal Investigator), Davies, Christopher J., Gollub, Jeremy, Webster, Teresa, Wong, Brant, Zhan, Yiping, Auton, Adam, (Principal Investigator), Campbell, Christopher L., Kong, Yu, Marcketta, Anthony, Yu, Fuli, (Project Leader), Antunes, Lilian, Bainbridge, Matthew, Sabo, Aniko, Huang, Zhuoyi, Coin, Lachlan J. M., Fang, Lin, Li, Qibin, Li, Zhenyu, Lin, Haoxiang, Liu, Binghang, Luo, Ruibang, Shao, Haojing, Xie, Yinlong, Ye, Chen, Yu, Chang, Zhang, Fan, Zheng, Hancheng, Zhu, Hongmei, Alkan, Can, Dal, Elif, Kahveci, Fatma, Garrison, Erik P., (Project Lead), Kural, Deniz, Lee, Wan-Ping, Leong, Wen Fung, Stromberg, Michael, Ward, Alistair N., Wu, Jiantao, Zhang, Mengyao, Daly, Mark J., (Principal Investigator), DePristo, Mark A., (Project Leader), Handsaker, Robert E., (Project Leader), Banks, Eric, Bhatia, Gaurav, del Angel, Guillermo, Genovese, Giulio, Li, Heng, Kashin, Seva, Nemesh, James C., Poplin, Ryan E., Yoon, Seungtai C., (Principal Investigator), Lihm, Jayon, Makarov, Vladimir, Clark, Andrew G., (Principal Investigator), Gottipati, Srikanth, Keinan, Alon, Rodriguez-Flores, Juan L., Rausch, Tobias, (Project Leader), Fritz, Markus H., Stütz, Adrian M., Beal, Kathryn, Datta, Avik, Herrero, Javier, Ritchie, Graham R. S., Zerbino, Daniel, Sabeti, Pardis C., (Principal Investigator), Shlyakhter, Ilya, Schaffner, Stephen F., Vitti, Joseph, Cooper, David N., (Principal Investigator), Ball, Edward V., Stenson, Peter D., Barnes, Bret, Bauer, Markus, Cheetham, Keira R., Cox, Anthony, Eberle, Michael, Kahn, Scott, Murray, Lisa, Peden, John, Shaw, Richard, Kenny, Eimear E., (Principal Investigator), Batzer, Mark A., (Principal Investigator), Konkel, Miriam K., Walker, Jerilyn A., MacArthur, Daniel G., (Principal Investigator), Lek, Monkol, Herwig, Ralf, Koboldt, Daniel C., Larson, David, Ye, Kai, Gravel, Simon, Swaroop, Anand, Chew, Emily, Lappalainen, Tuuli, (Principal Investigator), Erlich, Yaniv, (Principal Investigator), Gymrek, Melissa, Willems, Thomas Frederick, Simpson, Jared T., Shriver, Mark D., (Principal Investigator), Rosenfeld, Jeffrey A., (Principal Investigator), Montgomery, Stephen B., (Principal Investigator), De La Vega, Francisco M., (Principal Investigator), Byrnes, Jake K., Carroll, Andrew W., DeGorter, Marianne K., Lacroute, Phil, Maples, Brian K., Martin, Alicia R., Moreno-Estrada, Andres, Shringarpure, Suyash S., Zakharia, Fouad, Halperin, Eran, (Principal Investigator), Baran, Yael, Cerveira, Eliza, Hwang, Jaeho, Malhotra, Ankit, (Co-Project Lead), Plewczynski, Dariusz, Radew, Kamen, Romanovitch, Mallory, Zhang, Chengsheng, (Co-Project Lead), Hyland, Fiona C. L., Craig, David W., (Principal Investigator), Christoforides, Alexis, Homer, Nils, Izatt, Tyler, Kurdoglu, Ahmet A., Sinari, Shripad A., Squire, Kevin, Xiao, Chunlin, Sebat, Jonathan, (Principal Investigator), Antaki, Danny, Gujral, Madhusudan, Noor, Amina, Ye, Kenny, Burchard, Esteban G., (Principal Investigator), Hernandez, Ryan D., (Principal Investigator), Gignoux, Christopher R., Haussler, David, (Principal Investigator), Katzman, Sol J., Kent, James W., Howie, Bryan, Ruiz-Linares, Andres, (Principal Investigator), Dermitzakis, Emmanouil T., (Principal Investigator), Devine, Scott E., (Principal Investigator), Abecasis, Gonçalo R., (Principal Investigator) (Co-Chair), Kang, Hyun Min, (Project Leader), Kidd, Jeffrey M., (Principal Investigator), Blackwell, Tom, Caron, Sean, Chen, Wei, Emery, Sarah, Fritsche, Lars, Fuchsberger, Christian, Jun, Goo, Li, Bingshan, Lyons, Robert, Scheller, Chris, Sidore, Carlo, Song, Shiya, Sliwerska, Elzbieta, Taliun, Daniel, Tan, Adrian, Welch, Ryan, Wing, Mary Kate, Zhan, Xiaowei, Awadalla, Philip, (Principal Investigator), Hodgkinson, Alan, Li, Yun, Shi, Xinghua, (Principal Investigator), Quitadamo, Andrew, Lunter, Gerton, (Principal Investigator), McVean, Gil A., (Principal Investigator) (Co-Chair), Marchini, Jonathan L., (Principal Investigator), Myers, Simon, (Principal Investigator), Churchhouse, Claire, Delaneau, Olivier, Gupta-Hinch, Anjali, Kretzschmar, Warren, Iqbal, Zamin, Mathieson, Iain, Menelaou, Androniki, Rimmer, Andy, Xifara, Dionysia K., Oleksyk, Taras K., (Principal Investigator), Fu, Yunxin, (Principal Investigator), Liu, Xiaoming, Xiong, Momiao, Jorde, Lynn, (Principal Investigator), Witherspoon, David, Xing, Jinchuan, Browning, Brian L., (Principal Investigator), Browning, Sharon R., (Principal Investigator), Hormozdiari, Fereydoun, Sudmant, Peter H., Khurana, Ekta, (Principal Investigator), Hurles, Matthew E., (Principal Investigator), Albers, Cornelis A., Ayub, Qasim, Chen, Yuan, Colonna, Vincenza, Jostins, Luke, Walter, Klaudia, Xue, Yali, Abyzov, Alexej, Balasubramanian, Suganthi, Chen, Jieming, Clarke, Declan, Fu, Yao, Harmanci, Arif O., Jin, Mike, Lee, Donghoon, Liu, Jeremy, Mu, Xinmeng Jasmine, Zhang, Jing, Zhang, Yan, McCarroll, Steven A., (Principal Investigator), Hartl, Chris, Shakir, Khalid, Degenhardt, Jeremiah, Korbel, Jan O., (Principal Investigator) (Co-Chair), Meiers, Sascha, Raeder, Benjamin, Casale, Francesco Paolo, Stegle, Oliver, Lameijer, Eric-Wubbo, Ding, Li, (Principal Investigator), Hall, Ira, Lee, Charles, (Principal Investigator) (Co-Chair), Bafna, Vineet, Michaelson, Jacob, Gardner, Eugene J., (Project Leader), Mills, Ryan E., (Principal Investigator), Dayama, Gargi, Chen, Ken, (Principle Investigator), Fan, Xian, Chong, Zechen, Chen, Tenghui, Eichler, Evan E., (Principal Investigator) (Co-Chair), Chaisson, Mark J., Huddleston, John, Malig, Maika, Nelson, Bradley J., Parrish, Nicholas F., Blackburne, Ben, Lindsay, Sarah J., Ning, Zemin, Zhang, Yujun, Lam, Hugo, Sisu, Cristina, Gibbs, Richard A., (Principal Investigator) (Co-Chair), Challis, Danny, Evani, Uday S., Lu, James, Nagaswamy, Uma, Yu, Jin, Li, Wangshen, Marth, Gabor T., (Principal Investigator) (Co-Chair), Habegger, Lukas, Yu, Haiyuan, (Principal Investigator), Cunningham, Fiona, Dunham, Ian, Lage, Kasper, (Principal Investigator), Jespersen, Jakob Berg, Horn, Heiko, Tyler-Smith, Chris, (Principal Investigator) (Co-Chair), Gerstein, Mark B., (Principal Investigator) (Co-Chair), Kim, Donghoon, Desalle, Rob, Narechania, Apurva, Wilson Sayres, Melissa A., Bustamante, Carlos D., (Principal Investigator) (Co-Chair), Mendez, Fernando L., Poznik, David G., Underhill, Peter A., Coin, Lachlan, (Principal Investigator), Mittelman, David, Banerjee, Ruby, Cerezo, Maria, Fitzgerald, Thomas W., Louzada, Sandra, Massaia, Andrea, Ritchie, Graham R., Yang, Fengtang, Kalra, Divya, Hale, Walker, Dan, Xu, Flicek, Paul, (Principal Investigator) (Co-Chair), Clarke, Laura, (Project Lead), Sherry, Stephen T., (Principal Investigator) (Co-Chair), Chakravarti, Aravinda, (Co-Chair), Knoppers, Bartha M., (Co-Chair), Barnes, Kathleen C., Beiswanger, Christine, Cai, Hongyu, Cao, Hongzhi, Henn, Brenna, Jones, Danielle, Kaye, Jane S., Kent, Alastair, Kerasidou, Angeliki, Mathias, Rasika, Ossorio, Pilar N., Parker, Michael, Rotimi, Charles N., Royal, Charmaine D., Sandoval, Karla, Su, Yeyang, Tian, Zhongming, Tishkoff, Sarah, Via, Marc, Wang, Yuhong, Yang, Ling, Zhu, Jiayong, Bodmer, Walter, Bedoya, Gabriel, Cai, Zhiming, Gao, Yang, Chu, Jiayou, Peltonen, Leena, Garcia-Montero, Andres, Orfao, Alberto, Dutil, Julie, Martinez-Cruzado, Juan C., Mathias, Rasika A., Hennis, Anselm, Watson, Harold, McKenzie, Colin, Qadri, Firdausi, LaRocque, Regina, Deng, Xiaoyan, Asogun, Danny, Folarin, Onikepe, Happi, Christian, Omoniwa, Omonwunmi, Stremlau, Matt, Tariyal, Ridhi, Jallow, Muminatou, Joof, Fatoumatta Sisay, Corrah, Tumani, Rockett, Kirk, Kwiatkowski, Dominic, Kooner, Jaspal, Hiê`n, Trâ`n Tinh, Dunstan, Sarah J., Hang, Nguyen Thuy, Fonnie, Richard, Garry, Robert, Kanneh, Lansana, Moses, Lina, Schieffelin, John, Grant, Donald S., Gallo, Carla, Poletti, Giovanni, Saleheen, Danish, Rasheed, Asif, Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Vaydylevich, Yekaterina, Duncanson, Audrey, Dunn, Michael, Schloss, Jeffery A., and Yang, Huanming

Published
2015
Full Text
View/download PDF

22. Optogenetic modeling of human neuromuscular circuits in Duchenne muscular dystrophy with CRISPR and pharmacological corrections

Author

Paredes-Redondo, Amaia, primary, Harley, Peter, additional, Maniati, Eleni, additional, Ryan, David, additional, Louzada, Sandra, additional, Meng, Jinhong, additional, Kowala, Anna, additional, Fu, Beiyuan, additional, Yang, Fengtang, additional, Liu, Pentao, additional, Marino, Silvia, additional, Pourquié, Olivier, additional, Muntoni, Francesco, additional, Wang, Jun, additional, Lieberam, Ivo, additional, and Lin, Yung-Yao, additional

Published
2021
Full Text
View/download PDF

26. Additional file 1: of Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects

Author

Gonรงalves, Emanuel, Behan, Fiona, Louzada, Sandra, Arnol, Damien, Stronach, Euan, Fengtang Yang, Yusa, Kosuke, Stegle, Oliver, Iorio, Francesco, and Garnett, Mathew

Abstract

Figure S1. CRISPR data overview and quality assessment. Figure S2. Structural rearrangements association with CRISPR-Cas9 response. Figure S3. Gene copy-number ratios. Figure S4. FISH and M-FISH experiments. Figure S5. Crispy benchmark against CERES. (PDF 909 kb)

Published
2019
Full Text
View/download PDF

29. Structural variation of the malaria-associated human glycophorin A-B-E region

Author

Louzada, Sandra, primary, Algady, Walid, additional, Weyell, Eleanor, additional, Zuccherato, Luciana W., additional, Brajer, Paulina, additional, Almalki, Faisal, additional, Scliar, Marilia O, additional, Naslavsky, Michel S, additional, Yamamoto, Guilherme L, additional, Duarte, Yeda A O, additional, Passos-Bueno, Maria Rita, additional, Zatz, Mayana, additional, Yang, Fengtang, additional, and Hollox, Edward J, additional

Published
2019
Full Text
View/download PDF

30. Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome

Author

Shi, Wentao, primary, Louzada, Sandra, additional, Grigorova, Marina, additional, Massaia, Andrea, additional, Arciero, Elena, additional, Kibena, Laura, additional, Ge, Xiangyu Jack, additional, Chen, Yuan, additional, Ayub, Qasim, additional, Poolamets, Olev, additional, Tyler-Smith, Chris, additional, Punab, Margus, additional, Laan, Maris, additional, Yang, Fengtang, additional, Hallast, Pille, additional, and Xue, Yali, additional

Published
2019
Full Text
View/download PDF

31. Recurrent rearrangements of human amylase genes create multiple independent CNV series

Author

Shwan, Nzar A.A., Louzada, Sandra, Yang, Fengtang, and Armour, John A.L.

Subjects
CNV, adaptation, genomic mutation, genomic instability
Abstract

The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1.

Published
2017

32. Pericentromeric satellite RNAsas flexible protein partners in the regulation of nuclear structure

Author

Lopes, Mariana, Louzada, Sandra, Gama‐Carvalho, Margarida, and Chaves, Raquel

Abstract

Pericentromeric heterochromatin is mainly composed of satellite DNA sequences. Although being historically associated with transcriptional repression, some pericentromeric satellite DNA sequences are transcribed. The transcription events of pericentromeric satellite sequences occur in highly flexible biological contexts. Hence, the apparent randomness of pericentromeric satellite transcription incites the discussion about the attribution of biological functions. However, pericentromeric satellite RNAs have clear roles in the organization of nuclear structure. Silencing pericentromeric heterochromatin depends on pericentromeric satellite RNAs, that, in a feedback mechanism, contribute to the repression of pericentromeric heterochromatin. Moreover, pericentromeric satellite RNAs can also act as scaffolding molecules in condensate subnuclear structures (e.g., nuclear stress bodies). Since the formation/dissociation of nuclear condensates provides cell adaptability, pericentromeric satellite RNAs can be an epigenetic platform for regulating (sub)nuclear structure. We review current knowledge about pericentromeric satellite RNAs that, irrespective of the meaning of biological function, should be functionally addressed in regular and disease settings. This article is categorized under:RNA Methods > RNA Analyses in CellsRNA in Disease and Development > RNA in Disease The biological roles of pericentromeric satellite RNAsin nuclear architecture: in the epigenetic silencing of pericentromeric heterochromatin; and in scaffolding nuclear bodies formed by Liquid–liquid phase separation (LLPS). We hypothesize that satellite RNAsin nuclear bodies provide adaptability in changeable epigenetic environments. Additionally, satellite RNAoverexpression (by epigenetic deregulation) correlates with disease progression.

Published
2024
Full Text
View/download PDF

34. Abstract 391: Evolutionary trajectories andKRASgene dosage define pancreatic cancer phenotypes

Author

Mueller, Sebastian, primary, Engleitner, Thomas, additional, Maresch, Roman, additional, Zukowska, Magdalena, additional, Lange, Sebastian, additional, Kaltenbacher, Thorsten, additional, Konukiewitz, Björn, additional, Öllinger, Rupert, additional, Zwiebel, Maximilian, additional, Strong, Alex, additional, Yen, Hsi-Yu, additional, Banerjee, Ruby, additional, Louzada, Sandra, additional, Fu, Beiyuan, additional, Seidler, Barbara, additional, Götzfried, Juliana, additional, Schuck, Kathleen, additional, Hassan, Zonera, additional, Schönhuber, Nina, additional, Klein, Sabine, additional, Veltkamp, Christian, additional, Friedrich, Mathias, additional, Rad, Lena, additional, Barenboim, Maxim, additional, Ziegenhain, Christoph, additional, Hess, Julia, additional, Dovey, Oliver M., additional, Eser, Stefan, additional, Parekh, Swati, additional, Constantino-Casas, Fernando, additional, Rosa, Jorge de la, additional, Sierra, Marta I., additional, Fraga, Mario, additional, Mayerle, Julia, additional, Klöppel, Günter, additional, Schmid, Roland M., additional, Cadiñanos, Juan, additional, Liu, Pentao, additional, Vassiliou, George, additional, Weichert, Wilko, additional, Steiger, Katja, additional, Enard, Wolfgang, additional, Yang, Fengtang, additional, Unger, Kristian, additional, Schneider, Günter, additional, Varela, Ignacio, additional, Bradley, Allan, additional, Saur, Dieter, additional, and Rad, Roland, additional

Published
2018
Full Text
View/download PDF

36. Expansion of the HSFY gene family in pig lineages: HSFY expansion in suids

Author

Skinner, Benjamin M, Lachani, Kim, Sargent, Carole A, Yang, Fengtang, Ellis, Peter, Hunt, Toby, Fu, Beiyuan, Louzada, Sandra, Churcher, Carol, Tyler-Smith, Chris, Affara, Nabeel A, Skinner, Benjamin [0000-0002-7152-1167], Sargent, Carole [0000-0002-4205-3085], and Apollo - University of Cambridge Repository

Subjects
Male, DNA Repeat Expansion, Swine, Sus scrofa, Gene Amplification, QH301, Codon, Nonsense, Multigene Family, Y Chromosome, Testis, Animals, SF, QH426, Short Interspersed Nucleotide Elements, Transcription Factors
Abstract

BACKGROUND: Amplified gene families on sex chromosomes can harbour genes with important biological functions, especially relating to fertility. The Y-linked heat shock transcription factor (HSFY) family has become amplified on the Y chromosome of the domestic pig (Sus scrofa), in an apparently independent event to an HSFY expansion on the Y chromosome of cattle (Bos taurus). Although the biological functions of HSFY genes are poorly understood, they appear to be involved in gametogenesis in a number of mammalian species, and, in cattle, HSFY gene copy number may correlate with levels of fertility. RESULTS: We have investigated the HSFY family in domestic pig, and other suid species including warthog, bushpig, babirusa and peccaries. The domestic pig contains at least two amplified variants of HSFY, distinguished predominantly by presence or absence of a SINE within the intron. Both these variants are expressed in testis, and both are present in approximately 50 copies each in a single cluster on the short arm of the Y. The longer form has multiple nonsense mutations rendering it likely non-functional, but many of the shorter forms still have coding potential. Other suid species also have these two variants of HSFY, and estimates of copy number suggest the HSFY family may have amplified independently twice during suid evolution. CONCLUSIONS: The HSFY genes have become amplified in multiple species lineages independently. HSFY is predominantly expressed in testis in domestic pig, a pattern conserved with cattle, in which HSFY may play a role in fertility. Further investigation of the potential associations of HSFY with fertility and testis development may be of agricultural interest.

Published
2015

37. Targeted gene correction of FKRP by CRISPR/Cas9 restores functional glycosylation of α-dystroglycan in cortical neurons derived from human induced pluripotent stem cells

Author

Lana, Beatrice, primary, Kim, Jihee, additional, Ryan, David, additional, Konstantinidis, Evangelos, additional, Louzada, Sandra, additional, Fu, Beiyuan, additional, Yang, Fengtang, additional, Stemple, Derek L., additional, Liu, Pentao, additional, Muntoni, Francesco, additional, and Lin, Yung-Yao, additional

Published
2017
Full Text
View/download PDF

38. The pig X and Y Chromosomes: structure, sequence, and evolution.

Author

Skinner, Benjamin M, Sargent, Carole A, Churcher, Carol, Hunt, Toby, Herrero, Javier, Loveland, Jane E, Dunn, Matt, Louzada, Sandra, Fu, Beiyuan, Chow, William, Gilbert, James, Austin-Guest, Siobhan, Beal, Kathryn, Carvalho-Silva, Denise, Cheng, William, Gordon, Daria, Grafham, Darren, Hardy, Matt, Harley, Jo, Hauser, Heidi, Howden, Philip, Howe, Kerstin, Lachani, Kim, Ellis, Peter J.I., Kelly, Daniel, Kerry, Giselle, Kerwin, James, Ng, Bee Ling, Threadgold, Glen, Wileman, Thomas, Wood, Jonathan M D, Yang, Fengtang, Harrow, Jen, Affara, Nabeel A, Tyler-Smith, Chris, Skinner, Benjamin M, Sargent, Carole A, Churcher, Carol, Hunt, Toby, Herrero, Javier, Loveland, Jane E, Dunn, Matt, Louzada, Sandra, Fu, Beiyuan, Chow, William, Gilbert, James, Austin-Guest, Siobhan, Beal, Kathryn, Carvalho-Silva, Denise, Cheng, William, Gordon, Daria, Grafham, Darren, Hardy, Matt, Harley, Jo, Hauser, Heidi, Howden, Philip, Howe, Kerstin, Lachani, Kim, Ellis, Peter J.I., Kelly, Daniel, Kerry, Giselle, Kerwin, James, Ng, Bee Ling, Threadgold, Glen, Wileman, Thomas, Wood, Jonathan M D, Yang, Fengtang, Harrow, Jen, Affara, Nabeel A, and Tyler-Smith, Chris

Abstract

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.

Published
2015

39. Expansion of the HSFY gene family in pig lineages: HSFY expansion in suids

Author

Skinner, Benjamin M., Lachani, Kim, Sargent, Carole A, Yang, Fengtang, Ellis, Peter J.I., Hunt, Toby, Fu, Beiyuan, Louzada, Sandra, Churcher, Carol, Tyler-Smith, Chris, Affara, Nabeel A, Skinner, Benjamin M., Lachani, Kim, Sargent, Carole A, Yang, Fengtang, Ellis, Peter J.I., Hunt, Toby, Fu, Beiyuan, Louzada, Sandra, Churcher, Carol, Tyler-Smith, Chris, and Affara, Nabeel A

Abstract

BACKGROUND: Amplified gene families on sex chromosomes can harbour genes with important biological functions, especially relating to fertility. The Y-linked heat shock transcription factor (HSFY) family has become amplified on the Y chromosome of the domestic pig (Sus scrofa), in an apparently independent event to an HSFY expansion on the Y chromosome of cattle (Bos taurus). Although the biological functions of HSFY genes are poorly understood, they appear to be involved in gametogenesis in a number of mammalian species, and, in cattle, HSFY gene copy number may correlate with levels of fertility. RESULTS: We have investigated the HSFY family in domestic pig, and other suid species including warthog, bushpig, babirusa and peccaries. The domestic pig contains at least two amplified variants of HSFY, distinguished predominantly by presence or absence of a SINE within the intron. Both these variants are expressed in testis, and both are present in approximately 50 copies each in a single cluster on the short arm of the Y. The longer form has multiple nonsense mutations rendering it likely non-functional, but many of the shorter forms still have coding potential. Other suid species also have these two variants of HSFY, and estimates of copy number suggest the HSFY family may have amplified independently twice during suid evolution. CONCLUSIONS: The HSFY genes have become amplified in multiple species lineages independently. HSFY is predominantly expressed in testis in domestic pig, a pattern conserved with cattle, in which HSFY may play a role in fertility. Further investigation of the potential associations of HSFY with fertility and testis development may be of agricultural interest.

Published
2015

40. The pig X and Y Chromosomes: structure, sequence, and evolution

Author

Skinner, Benjamin M., primary, Sargent, Carole A., additional, Churcher, Carol, additional, Hunt, Toby, additional, Herrero, Javier, additional, Loveland, Jane E., additional, Dunn, Matt, additional, Louzada, Sandra, additional, Fu, Beiyuan, additional, Chow, William, additional, Gilbert, James, additional, Austin-Guest, Siobhan, additional, Beal, Kathryn, additional, Carvalho-Silva, Denise, additional, Cheng, William, additional, Gordon, Daria, additional, Grafham, Darren, additional, Hardy, Matt, additional, Harley, Jo, additional, Hauser, Heidi, additional, Howden, Philip, additional, Howe, Kerstin, additional, Lachani, Kim, additional, Ellis, Peter J.I., additional, Kelly, Daniel, additional, Kerry, Giselle, additional, Kerwin, James, additional, Ng, Bee Ling, additional, Threadgold, Glen, additional, Wileman, Thomas, additional, Wood, Jonathan M.D., additional, Yang, Fengtang, additional, Harrow, Jen, additional, Affara, Nabeel A., additional, and Tyler-Smith, Chris, additional

Published
2015
Full Text
View/download PDF

41. Correction: Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association

Author

Ding, Zhihao, primary, Ni, Yunyun, additional, Timmer, Sander W., additional, Lee, Bum-Kyu, additional, Battenhouse, Anna, additional, Louzada, Sandra, additional, Yang, Fengtang, additional, Dunham, Ian, additional, Crawford, Gregory E., additional, Lieb, Jason D., additional, Durbin, Richard, additional, Iyer, Vishwanath R., additional, and Birney, Ewan, additional

Published
2015
Full Text
View/download PDF

43. Copy number variation arising from gene conversion on the human Y chromosome.

Author

Shi, Wentao, Massaia, Andrea, Louzada, Sandra, Banerjee, Ruby, Hallast, Pille, Chen, Yuan, Bergström, Anders, Gu, Yong, Leonard, Steven, Quail, Michael A., Ayub, Qasim, Yang, Fengtang, Tyler-Smith, Chris, and Xue, Yali

Subjects
DNA copy number variations, GENE conversion, Y chromosome, NON-coding RNA, POLYMERASE chain reaction, PHYLOGENY
Abstract

We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0–3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0–2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

45. Expansion of the HSFY gene family in pig lineages

Author

Skinner, Benjamin M, primary, Lachani, Kim, additional, Sargent, Carole A, additional, Yang, Fengtang, additional, Ellis, Peter JI, additional, Hunt, Toby, additional, Fu, Beiyuan, additional, Louzada, Sandra, additional, Churcher, Carol, additional, Tyler-Smith, Chris, additional, and Affara, Nabeel A, additional

Published
2014
Full Text
View/download PDF

46. The pig X and Y chromosomes: structure, sequence and evolution

Author

Skinner, Benjamin M, primary, Sargent, Carole A, additional, Churcher, Carol, additional, Hunt, Toby, additional, Herrero, Javier, additional, Loveland, Jane, additional, Dunn, Matt, additional, Louzada, Sandra, additional, Fu, Beiyuan, additional, Chow, William, additional, Gilbert, James, additional, Austin-Guest, Siobhan, additional, Beal, Kathryn, additional, Carvalho-Silva, Denise, additional, Cheng, William, additional, Gordon, Daria, additional, Grafham, Darren, additional, Hardy, Matt, additional, Harley, Jo, additional, Hauser, Heidi, additional, Howden, Philip, additional, Howe, Kerstin, additional, Lachani, Kim, additional, Ellis, Peter JI, additional, Kelly, Daniel, additional, Kerry, Giselle, additional, Kerwin, James, additional, Ng, Bee Ling, additional, Threadgold, Glen, additional, Wileman, Thomas, additional, Wood, Jonathan MD, additional, Yang, Fengtang, additional, Harrow, Jen, additional, Affara, Nabeel A, additional, and Tyler-Smith, Chris, additional

Published
2014
Full Text
View/download PDF

47. Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association

Author

Ding, Zhihao, primary, Ni, Yunyun, additional, Timmer, Sander W., additional, Lee, Bum-Kyu, additional, Battenhouse, Anna, additional, Louzada, Sandra, additional, Yang, Fengtang, additional, Dunham, Ian, additional, Crawford, Gregory E., additional, Lieb, Jason D., additional, Durbin, Richard, additional, Iyer, Vishwanath R., additional, and Birney, Ewan, additional

Published
2014
Full Text
View/download PDF

48. Evolutionary routes and KRASdosage define pancreatic cancer phenotypes

Author

Mueller, Sebastian, Engleitner, Thomas, Maresch, Roman, Zukowska, Magdalena, Lange, Sebastian, Kaltenbacher, Thorsten, Konukiewitz, Björn, Öllinger, Rupert, Zwiebel, Maximilian, Strong, Alex, Yen, Hsi-Yu, Banerjee, Ruby, Louzada, Sandra, Fu, Beiyuan, Seidler, Barbara, Götzfried, Juliana, Schuck, Kathleen, Hassan, Zonera, Arbeiter, Andreas, Schönhuber, Nina, Klein, Sabine, Veltkamp, Christian, Friedrich, Mathias, Rad, Lena, Barenboim, Maxim, Ziegenhain, Christoph, Hess, Julia, Dovey, Oliver M., Eser, Stefan, Parekh, Swati, Constantino-Casas, Fernando, de la Rosa, Jorge, Sierra, Marta I., Fraga, Mario, Mayerle, Julia, Klöppel, Günter, Cadiñanos, Juan, Liu, Pentao, Vassiliou, George, Weichert, Wilko, Steiger, Katja, Enard, Wolfgang, Schmid, Roland M., Yang, Fengtang, Unger, Kristian, Schneider, Günter, Varela, Ignacio, Bradley, Allan, Saur, Dieter, and Rad, Roland

Abstract

The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRASin human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUTlevels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1or Nfkb2), which collaborate with heterozygous KrasMUTin driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.

Published
2018
Full Text
View/download PDF

50. Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

Author

Poznik, G David, Xue, Yali, Mendez, Fernando L, Willems, Thomas F, Massaia, Andrea, Wilson Sayres, Melissa A, Ayub, Qasim, McCarthy, Shane A, Narechania, Apurva, Kashin, Seva, Chen, Yuan, Banerjee, Ruby, Rodriguez-Flores, Juan L, Cerezo, Maria, Shao, Haojing, Gymrek, Melissa, Malhotra, Ankit, Louzada, Sandra, Desalle, Rob, Ritchie, Graham R S, Cerveira, Eliza, Fitzgerald, Tomas W, Garrison, Erik, Marcketta, Anthony, Mittelman, David, Romanovitch, Mallory, Zhang, Chengsheng, Zheng-Bradley, Xiangqun, Abecasis, Gonçalo R, McCarroll, Steven A, Flicek, Paul, Underhill, Peter A, Coin, Lachlan, Zerbino, Daniel R, Yang, Fengtang, Lee, Charles, Clarke, Laura, Auton, Adam, Erlich, Yaniv, Handsaker, Robert E, Bustamante, Carlos D, and Tyler-Smith, Chris

Abstract

We report the sequences of 1,244 human Y chromosomes randomly ascertained from 26 worldwide populations by the 1000 Genomes Project. We discovered more than 65,000 variants, including single-nucleotide variants, multiple-nucleotide variants, insertions and deletions, short tandem repeats, and copy number variants. Of these, copy number variants contribute the greatest predicted functional impact. We constructed a calibrated phylogenetic tree on the basis of binary single-nucleotide variants and projected the more complex variants onto it, estimating the number of mutations for each class. Our phylogeny shows bursts of extreme expansion in male numbers that have occurred independently among each of the five continental superpopulations examined, at times of known migrations and technological innovations.

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results