Genetic Structures Commons^™

Review On Molecular Genetic Basis Of Hypertrophic Cardiomyopathy, Derek Pok Him Lee

Journal of the Hong Kong College of Cardiology

Hypertrophic cardiomyopathy (HCM) is one of the most common types of inherited cardiomyopathy with a wide range of clinical manifestations ranging from subtle myocardial hypertrophy to debilitating heart failure, cardiac arrhythmias, and sudden cardiac death. We reviewed the literature on the latest knowledge regarding the pathophysiology and molecular genetic basis of HCM. This will include laboratory studies on animal models and human pluripotent stem-cell derived cardiomyocytes and the theory of proximal mechanisms involving calcium handling and energy expenditure underlying HCM. The current review will also illustrate the pathogenicity of various associated genetic variants, genotype-phenotype correlation and the optimal approach to …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …

A Multi-Omics Framework Reveals Strawberry Flavor Genes And Their Regulatory Elements, Zhen Fan, Denise M Tieman, Steven J Knapp, Philipp Zerbe, Randi Famula, Christopher R Barbey, Kevin M Folta, Rodrigo R Amadeu, Manbo Lee, Youngjae Oh, Seonghee Lee, Vance M Whitaker

Faculty, Staff and Student Publications

Flavor is essential to consumer preference of foods and is an increasing focus of plant breeding programs. In fruit crops, identifying genes underlying volatile organic compounds has great promise to accelerate flavor improvement, but polyploidy and heterozygosity in many species have slowed progress. Here we use octoploid cultivated strawberry to demonstrate how genomic heterozygosity, transcriptomic intricacy and fruit metabolomic diversity can be treated as strengths and leveraged to uncover fruit flavor genes and their regulatory elements. Multi-omics datasets were generated including an expression quantitative trait loci map with 196 diverse breeding lines, haplotype-phased genomes of a highly-flavored breeding selection, a …

A Saturated Map Of Common Genetic Variants Associated With Human Height, Loïc Yengo, Sailaja Vedantam, Eirini Marouli, Julia Sidorenko, Eric Bartell, Saori Sakaue, Marielisa Graff, Anders U Eliasen, Yunxuan Jiang, Sridharan Raghavan, Jenkai Miao, Joshua D Arias, Sarah E Graham, Ronen E Mukamel, Cassandra N Spracklen, Xianyong Yin, Shyh-Huei Chen, Teresa Ferreira, Heather H Highland, Yingjie Ji, Tugce Karaderi, Kuang Lin, Kreete Lüll, Deborah E Malden, Carolina Medina-Gomez, Moara Machado, Amy Moore, Sina Rüeger, Xueling Sim, Scott Vrieze, Tarunveer S Ahluwalia, Masato Akiyama, Matthew A Allison, Marcus Alvarez, Mette K Andersen, Alireza Ani, Vivek Appadurai, Liubov Arbeeva, Seema Bhaskar, Lawrence F Bielak, Sailalitha Bollepalli, Lori L Bonnycastle, Jette Bork-Jensen, Jonathan P Bradfield, Yuki Bradford, Peter S Braund, Jennifer A Brody, Kristoffer S Burgdorf, Brian E Cade, Hui Cai, Qiuyin Cai, Archie Campbell, Marisa Cañadas-Garre, Eulalia Catamo, Jin-Fang Chai, Xiaoran Chai, Li-Ching Chang, Yi-Cheng Chang, Chien-Hsiun Chen, Alessandra Chesi, Seung Hoan Choi, Ren-Hua Chung, Massimiliano Cocca, Maria Pina Concas, Christian Couture, Gabriel Cuellar-Partida, Rebecca Danning, E Warwick Daw, Frauke Degenhard, Graciela E Delgado, Alessandro Delitala, Ayse Demirkan, Xuan Deng, Poornima Devineni, Alexander Dietl, Maria Dimitriou, Latchezar Dimitrov, Rajkumar Dorajoo, Arif B Ekici, Jorgen E Engmann, Zammy Fairhurst-Hunter, Aliki-Eleni Farmaki, Jessica D Faul, Juan-Carlos Fernandez-Lopez, Lukas Forer, Margherita Francescatto, Sandra Freitag-Wolf, Christian Fuchsberger, Tessel E Galesloot, Yan Gao, Zishan Gao, Frank Geller, Olga Giannakopoulou, Franco Giulianini, Anette P Gjesing, Anuj Goel, Scott D Gordon, Mathias Gorski, Jakob Grove, Xiuqing Guo, Stefan Gustafsson, Jeffrey Haessler, Thomas F Hansen, Aki S Havulinna, Simon J Haworth, Jing He, Nancy Heard-Costa, Prashantha Hebbar, George Hindy, Yuk-Lam A Ho, Edith Hofer, Elizabeth Holliday, Katrin Horn, Whitney E Hornsby, Jouke-Jan Hottenga, Hongyan Huang, Jie Huang, Alicia Huerta-Chagoya, Jennifer E Huffman, Yi-Jen Hung, Shaofeng Huo, Mi Yeong Hwang, Hiroyuki Iha, Daisuke D Ikeda, Masato Isono, Anne U Jackson, Susanne Jäger, Iris E Jansen, Ingegerd Johansson, Jost B Jonas, Anna Jonsson, Torben Jørgensen, Ioanna-Panagiota Kalafati, Masahiro Kanai, Stavroula Kanoni, Line L Kårhus, Anuradhani Kasturiratne, Tomohiro Katsuya, Takahisa Kawaguchi, Rachel L Kember, Katherine A Kentistou, Han-Na Kim, Young Jin Kim, Marcus E Kleber, Maria J Knol, Azra Kurbasic, Marie Lauzon, Phuong Le, Rodney Lea, Jong-Young Lee, Hampton L Leonard, Shengchao A Li, Xiaohui Li, Xiaoyin Li, Jingjing Liang, Honghuang Lin, Shih-Yi Lin, Jun Liu, Xueping Liu, Ken Sin Lo, Jirong Long, Laura Lores-Motta, Jian'an Luan, Valeriya Lyssenko, Leo-Pekka Lyytikäinen, Anubha Mahajan, Vasiliki Mamakou, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Manuel Mattheisen, Laven Mavarani, Aaron F Mcdaid, Karina Meidtner, Tori L Melendez, Josep M Mercader, Yuri Milaneschi, Jason E Miller, Iona Y Millwood, Pashupati P Mishra, Ruth E Mitchell, Line T Møllehave, Anna Morgan, Soeren Mucha, Matthias Munz, Masahiro Nakatochi, Christopher P Nelson, Maria Nethander, Chu Won Nho, Aneta A Nielsen, Ilja M Nolte, Suraj S Nongmaithem, Raymond Noordam, Ioanna Ntalla, Teresa Nutile, Anita Pandit, Paraskevi Christofidou, Katri Pärna, Marc Pauper, Eva R B Petersen, Liselotte V Petersen, Niina Pitkänen, Ozren Polašek, Alaitz Poveda, Michael H Preuss, Saiju Pyarajan, Laura M Raffield, Hiromi Rakugi, Julia Ramirez, Asif Rasheed, Dennis Raven, Nigel W Rayner, Carlos Riveros, Rebecca Rohde, Daniela Ruggiero, Sanni E Ruotsalainen, Kathleen A Ryan, Maria Sabater-Lleal, Richa Saxena, Markus Scholz, Anoop Sendamarai, Botong Shen, Jingchunzi Shi, Jae Hun Shin, Carlo Sidore, Colleen M Sitlani, Roderick C Slieker, Roelof A J Smit, Albert V Smith, Jennifer A Smith, Laura J Smyth, Lorraine Southam, Valgerdur Steinthorsdottir, Liang Sun, Fumihiko Takeuchi, Divya Sri Priyanka Tallapragada, Kent D Taylor, Bamidele O Tayo, Catherine Tcheandjieu, Natalie Terzikhan, Paola Tesolin, Alexander Teumer, Elizabeth Theusch, Deborah J Thompson, Gudmar Thorleifsson, Paul R H J Timmers, Stella Trompet, Constance Turman, Simona Vaccargiu, Sander W Van Der Laan, Peter J Van Der Most, Jan B Van Klinken, Jessica Van Setten, Shefali S Verma, Niek Verweij, Yogasudha Veturi, Carol A Wang, Chaolong Wang, Lihua Wang, Zhe Wang, Helen R Warren, Wen Bin Wei, Ananda R Wickremasinghe, Matthias Wielscher, Kerri L Wiggins, Bendik S Winsvold, Andrew Wong, Yang Wu, Matthias Wuttke, Rui Xia, Tian Xie, Ken Yamamoto, Jingyun Yang, Jie Yao, Hannah Young, Noha A Yousri, Lei Yu, Lingyao Zeng, Weihua Zhang, Xinyuan Zhang, Jing-Hua Zhao, Wei Zhao, Wei Zhou, Martina E Zimmermann, Magdalena Zoledziewska, Linda S Adair, Hieab H H Adams, Carlos A Aguilar-Salinas, Fahd Al-Mulla, Donna K Arnett, Folkert W Asselbergs, Bjørn Olav Åsvold, John Attia, Bernhard Banas, Stefania Bandinelli, David A Bennett, Tobias Bergler, Dwaipayan Bharadwaj, Ginevra Biino, Hans Bisgaard, Eric Boerwinkle, Carsten A Böger, Klaus Bønnelykke, Dorret I Boomsma, Anders D Børglum, Judith B Borja, Claude Bouchard, Donald W Bowden, Ivan Brandslund, Ben Brumpton, Julie E Buring, Mark J Caulfield, John C Chambers, Giriraj R Chandak, Stephen J Chanock, Nish Chaturvedi, Yii-Der Ida Chen, Zhengming Chen, Ching-Yu Cheng, Ingrid E Christophersen, Marina Ciullo, John W Cole, Francis S Collins, Richard S Cooper, Miguel Cruz, Francesco Cucca, L Adrienne Cupples, Michael J Cutler, Scott M Damrauer, Thomas M Dantoft, Gert J De Borst, Lisette C P G M De Groot, Philip L De Jager, Dominique P V De Kleijn, H Janaka De Silva, George V Dedoussis, Anneke I Den Hollander, Shufa Du, Douglas F Easton, Petra J M Elders, A Heather Eliassen, Patrick T Ellinor, Sölve Elmståhl, Jeanette Erdmann, Michele K Evans, Diane Fatkin, Bjarke Feenstra, Mary F Feitosa, Luigi Ferrucci, Ian Ford, Myriam Fornage, Andre Franke, Paul W Franks, Barry I Freedman, Paolo Gasparini, Christian Gieger, Giorgia Girotto, Michael E Goddard, Yvonne M Golightly, Clicerio Gonzalez-Villalpando, Penny Gordon-Larsen, Harald Grallert, Struan F A Grant, Niels Grarup, Lyn Griffiths, Vilmundur Gudnason, Christopher Haiman, Hakon Hakonarson, Torben Hansen, Catharina A Hartman, Andrew T Hattersley, Caroline Hayward, Susan R Heckbert, Chew-Kiat Heng, Christian Hengstenberg, Alex W Hewitt, Haretsugu Hishigaki, Carel B Hoyng, Paul L Huang, Wei Huang, Steven C Hunt, Kristian Hveem, Elina Hyppönen, William G Iacono, Sahoko Ichihara, M Arfan Ikram, Carmen R Isasi, Rebecca D Jackson, Marjo-Riitta Jarvelin, Zi-Bing Jin, Karl-Heinz Jöckel, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Mika Kähönen, Yoichiro Kamatani, Kui Dong Kang, Jaakko Kaprio, Sharon L R Kardia, Fredrik Karpe, Norihiro Kato, Frank Kee, Thorsten Kessler, Amit V Khera, Chiea Chuen Khor, Lambertus A L M Kiemeney, Bong-Jo Kim, Eung Kweon Kim, Hyung-Lae Kim, Paulus Kirchhof, Mika Kivimaki, Woon-Puay Koh, Heikki A Koistinen, Genovefa D Kolovou, Jaspal S Kooner, Charles Kooperberg, Anna Köttgen, Peter Kovacs, Adriaan Kraaijeveld, Peter Kraft, Ronald M Krauss, Meena Kumari, Zoltan Kutalik, Markku Laakso, Leslie A Lange, Claudia Langenberg, Lenore J Launer, Loic Le Marchand, Hyejin Lee, Nanette R Lee, Terho Lehtimäki, Huaixing Li, Liming Li, Wolfgang Lieb, Xu Lin, Lars Lind, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Markus Loeffler, Barry London, Steven A Lubitz, Stephen J Lye, David A Mackey, Reedik Mägi, Patrik K E Magnusson, Gregory M Marcus, Pedro Marques Vidal, Nicholas G Martin, Winfried März, Fumihiko Matsuda, Robert W Mcgarrah, Matt Mcgue, Amy Jayne Mcknight, Sarah E Medland, Dan Mellström, Andres Metspalu, Braxton D Mitchell, Paul Mitchell, Dennis O Mook-Kanamori, Andrew D Morris, Lorelei A Mucci, Patricia B Munroe, Mike A Nalls, Saman Nazarian, Amanda E Nelson, Matt J Neville, Christopher Newton-Cheh, Christopher S Nielsen, Markus M Nöthen, Claes Ohlsson, Albertine J Oldehinkel, Lorena Orozco, Katja Pahkala, Päivi Pajukanta, Colin N A Palmer, Esteban J Parra, Cristian Pattaro, Oluf Pedersen, Craig E Pennell, Brenda W J H Penninx, Louis Perusse, Annette Peters, Patricia A Peyser, David J Porteous, Danielle Posthuma, Chris Power, Peter P Pramstaller, Michael A Province, Qibin Qi, Jia Qu, Daniel J Rader, Olli T Raitakari, Sarju Ralhan, Loukianos S Rallidis, Dabeeru C Rao, Susan Redline, Dermot F Reilly, Alexander P Reiner, Sang Youl Rhee, Paul M Ridker, Michiel Rienstra, Samuli Ripatti, Marylyn D Ritchie, Dan M Roden, Frits R Rosendaal, Jerome I Rotter, Igor Rudan, Femke Rutters, Charumathi Sabanayagam, Danish Saleheen, Veikko Salomaa, Nilesh J Samani, Dharambir K Sanghera, Naveed Sattar, Börge Schmidt, Helena Schmidt, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Laura J Scott, Rodney J Scott, Peter Sever, Eric J Shiroma, M Benjamin Shoemaker, Xiao-Ou Shu, Eleanor M Simonsick, Mario Sims, Jai Rup Singh, Andrew B Singleton, Moritz F Sinner, J Gustav Smith, Harold Snieder, Tim D Spector, Meir J Stampfer, Klaus J Stark, David P Strachan, Leen M 'T Hart, Yasuharu Tabara, Hua Tang, Jean-Claude Tardif, Thangavel A Thanaraj, Nicholas J Timpson, Anke Tönjes, Angelo Tremblay, Tiinamaija Tuomi, Jaakko Tuomilehto, Maria-Teresa Tusié-Luna, Andre G Uitterlinden, Rob M Van Dam, Pim Van Der Harst, Nathalie Van Der Velde, Cornelia M Van Duijn, Natasja M Van Schoor, Veronique Vitart, Uwe Völker, Peter Vollenweider, Henry Völzke, Niels H Wacher-Rodarte, Mark Walker, Ya Xing Wang, Nicholas J Wareham, Richard M Watanabe, Hugh Watkins, David R Weir, Thomas M Werge, Elisabeth Widen, Lynne R Wilkens, Gonneke Willemsen, Walter C Willett, James F Wilson, Tien-Yin Wong, Jeong-Taek Woo, Alan F Wright, Jer-Yuarn Wu, Huichun Xu, Chittaranjan S Yajnik, Mitsuhiro Yokota, Jian-Min Yuan, Eleftheria Zeggini, Babette S Zemel, Wei Zheng, Xiaofeng Zhu, Joseph M Zmuda, Alan B Zonderman, John-Anker Zwart, Daniel I Chasman, Yoon Shin Cho, Iris M Heid, Mark I Mccarthy, Maggie C Y Ng, Christopher J O'Donnell, Fernando Rivadeneira, Unnur Thorsteinsdottir, Yan V Sun, E Shyong Tai, Michael Boehnke, Panos Deloukas, Anne E Justice, Cecilia M Lindgren, Ruth J F Loos, Karen L Mohlke, Kari E North, Kari Stefansson, Robin G Walters, Thomas W Winkler, Kristin L Young, Po-Ru Loh, Jian Yang, Tõnu Esko, Themistocles L Assimes, Adam Auton, Goncalo R Abecasis, Cristen J Willer, Adam E Locke, Sonja I Berndt, Guillaume Lettre, Timothy M Frayling, Yukinori Okada, Andrew R Wood, Peter M Visscher, Joel N Hirschhorn

Faculty, Staff and Student Publications

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the …

Svat: Secure Outsourcing Of Variant Annotation And Genotype Aggregation, Miran Kim, Su Wang, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

BACKGROUND: Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions.

RESULTS: We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at …

A Genome-Wide Screen Identifies Pdpk1 As A Target To Enhance The Efficacy Of Mek1/2 Inhibitors, Weijia Cai, Nicole A. Wilski, Timothy J. Purwin, Megane Vernon, Manoela Tiago, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Melanomas frequently harbor activating NRAS mutations. However, limited advance has been made in developing targeted therapy options for NRAS mutant melanoma patients. MEK inhibitors (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPR-Cas9-based screen and demonstrated that loss of Phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacological and molecular approaches. Combined PDPK1 inhibitors (PDPK1i) with MEKi suppressed NRAS mutant xenograft growth and induced gasdermin E-associated pyroptosis. In an immune-competent …

Induced Cytotoxicity In Crebbp/Ep300mut Head And Neck Squamous Cell Carcinoma, Thomaia Pamplin

Dissertations and Theses (Open Access)

INDUCED CYOTOXICTY IN CREBBP/EP300mut HEAD AND NECK SQUAMOUS CELL CARCINOMA

Thomaia Pamplin

Advisor: Curtis Pickering, Ph.D.

Background: Head and neck squamous cell carcinoma HNSCC is the most common malignancy in the head and neck. Most cases are found in advanced stages and depending on the location can be treated with surgical resection and/or radiation (XRT), chemotherapy, or chemoradiation. Our lab groups have identified that HNSCC with a mutation in its CREBBP/EP300 genes can be sensitized to XRT when the histone acetyltransferase activity of CREBBP/EP300 is inhibited. This radiosensitization manifests in the form of increased cell death for …

Non-Alcoholic Fatty Liver Disease And Depression: Evidence For Genotype × Environment Interaction In Mexican Americans, Eron G. Manusov, Vincent P. Diego, Khalid Sheikh, Sandra Laston, John Blangero, Sarah Williams-Blangero

School of Medicine Publications

This study examines the impact of G × E interaction effects on non-alcoholic fatty liver disease (NAFLD) among Mexican Americans in the Rio Grande Valley (RGV) of South Texas. We examined potential G × E interaction using variance components models and likelihood-based statistical inference in the phenotypic expression of NAFLD, including hepatic steatosis and hepatic fibrosis (identified using vibration controlled transient elastography and controlled attenuation parameter measured by the FibroScan Device). We screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G × E interactions for hepatic fibrosis × BDI-II. These findings provide evidence that genetic factors …

Identification Of Healthspan-Promoting Genes In Caenorhabditis Elegans Based On A Human Gwas Study, Nadine Saul, Ineke Dhondt, Mikko Kuokkanen, Markus Perola, Clara Verschuuren, Brecht Wouters, Henrik Von Chrzanowski, Winnok H. De Vos, Liesbet Temmerman, Walter Luyten

School of Medicine Publications

To find drivers of healthy ageing, a genome-wide association study (GWAS) was performed in healthy and unhealthy older individuals. Healthy individuals were defined as free from cardiovascular disease, stroke, heart failure, major adverse cardiovascular event, diabetes, dementia, cancer, chronic obstructive pulmonary disease (COPD), asthma, rheumatism, Crohn’s disease, malabsorption or kidney disease. Six single nucleotide polymorphisms (SNPs) with unknown function associated with ten human genes were identified as candidate healthspan markers. Thirteen homologous or closely related genes were selected in the model organism C. elegans for evaluating healthspan after targeted RNAi-mediated knockdown using pathogen resistance, muscle integrity, chemotaxis index and the …

Conservation And Divergence In The Heterochronic Pathway Of C. Elegans And C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic pathway of Caenorhabditis elegans is exemplary as a mechanism of developmental timing: mutations in genes of this pathway alter the relative timing of diverse developmental events independent of spatial or cell type specific regulation. It is the most thoroughly characterized developmental timing pathway known. Most of the heterochronic genes are conserved across great evolutionary time, and a few homologs seem to have developmental timing roles in certain contexts. The degree to which other organisms have explicit developmental timing mechanisms, and what factors comprise those mechanisms, isn’t generally known.

Developmental pathways evolve even if the resulting morphology remains the …

Modeling The Role Of Cyclin C In Connecting Stress-Induced Mitochondrial Fission To Apoptosis, Steven J. Doyle, Randy Strich

Rowan-Virtua Research Day

For normal cell function, exogenous signals must be correctly interpreted, and the proper response executed. The mitochondria are key regulatory nodes of cellular fate. For example, mitochondria undergo fission and fusion cycles depending on the energetic needs of the cell. Additionally, regulated cell death pathways also function at the mitochondria. Cyclin C is a transcriptional regulator of stress response and growth control genes. Following stress, a portion of cyclin C translocates to the cytoplasm, where it interacts with both the mitochondrial fission and apoptotic machinery. Based on these findings, we hypothesize that Cyclin C represents a key mediator linking transcription …

Substrate-Specific Effect On Sirtuin Conformation And Oligomerization, Jie Yang, Shannon L. Dwyer, Nathan I. Nicely, Brian P. Weiser

Rowan-Virtua Research Day

Human sirtuins are a family of nicotinamide adenine dinucleotide (NAD +)-dependent enzymes that are responsible for removing acyl modifications from lysine residues. Sirtuins are involved in the formation and proliferation of cancers and are thought to regulate the progression of neurodegenerative diseases. Although sirtuins can be pharmacologically targeted by small molecules, it is not easy to modulate the substrate selectivity of sirtuins despite the chemical diversity of their substrates. Here, we report substrate-specific effects on sirtuin conformation and oligomerization that regulate enzyme deacylase activity. We used fluorescent acyl peptide probes to study substrate interactions with two sirtuin isoforms: SIRT2 and …

Ung2 And Rpa Activity On Ssdna-Dsdna Junctions, Kathy Chen, Sharon Greenwood, Brian P. Weiser

Rowan-Virtua Research Day

Uracil DNA glycosylase, or UNG2, is an enzyme that is involved in DNA repair. Its primary job is to eliminate harmful uracil bases from DNA strands. To do this, the enzyme is assisted by replication protein A (RPA). RPA helps UNG2 in the identification of uracil bases by targeting UNG2 activity near ssDNA-dsDNA junctions (1-3). The results from assays presented here agree with published findings that showed UNG2 is heavily targeted by RPA to uracil bases that are close to ssDNA-dsDNA junctions (for example, uracil located 9 bps from the junction as opposed to 33 bps) (1,2). However, these previous …

Mendelian Randomization Supports Bidirectional Causality Between Telomere Length And Clonal Hematopoiesis Of Indeterminate Potential, Tetsushi Nakao, Alexander G. Bick, Margaret A. Taub, Seyedeh M. Zekavat, Md M. Uddin, Abhishek Niroula, Juan M. Peralta, Joanne E. Curran, John Blangero

School of Medicine Publications

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies …

Assessing Identification Of Newly Diagnosed Breast Cancer Patients For Referral To Genetic Counseling, Corinne Marie Locke

Theses and Dissertations

Since 1998, the National Comprehensive Cancer Network (NCCN) guidelines have specified clinical indications for genetic testing for breast cancer susceptibility genes, but retrospective studies have shown that, despite meeting the NCCN criteria, patients are not always advised of the option of genetic testing. Further compounding this issue, studies have shown that cancer family history intake and documented family history can be incomplete even when taken by oncology providers. At this study site and other cancer centers in the country, patients with a new diagnosis of breast cancer are referred for genetic counseling by their cancer care team if they are …

Evaluation Of Interactions Of Covid Nonstructural Proteins 3, 5, And 6 With Human Proteins And Potentially Therapeutic Molecules, Jessica Huitsing

Honors Undergraduate Theses

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2, or SARS-CoV-2, has been ongoing for over two years. The virus spreads easily and is more unpredictable than well-known viruses like the flu, making it important to have reliable combative measures before we fully drop non-vaccine preventive actions, like mask-wearing.Therefore, we used computational protein modeling to investigate the interactions of three nonstructural proteins (abbreviated Nsp) encoded in the viral RNA genome– Nsp3, Nsp5, and Nsp6 – which are involved in the viral life cycle, with human P-type polyamine transporting ATPases ATP13A2 and ATP13A3, whose disease symptoms when mutated mimic …

The Significance Of Cell-Surface Α2,3-Linked Sialic Acid In Osteoclasts, Christopher S. Harding

EWU Masters Thesis Collection

Osteoclasts are giant, multinucleated cells that, alongside osteoblasts, are central to maintaining physiologically healthy bone. The functions of osteoclasts and osteoblasts-degrading and depositing bone matrix, respectively-are paired in healthy bone tissue, thereby yielding no net bone loss or deposition. When these functions become imbalanced, it results in net bone loss or gain, depending on which cell type is being outcompeted. Osteoporosis is one of the most common pathologies stemming from such an imbalance, and predominantly affects postmenopausal women, as the ablation of circulating estrogen-a pro-death signal for osteoclasts-causes a prolongation of osteoclast lifespan and consequent lengthening of their resorptive activity. …

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …

Gene Electrotransfer Of Fgf2 Enhances Collagen Scaffold Biocompatibility, Carly Boye, Kyle Cristensen, Kamal Asadipour, Scott Declemente, Michael Francis, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Tendon injuries are a common athletic injury that have been increasing in prevalence. While there are current clinical treatments for tendon injuries, they have relatively long recovery times and often do not restore native function of the tendon. In the current study, gene electrotransfer (GET) parameters for delivery to the skin were optimized with monophasic and biphasic pulses with reporter and effector genes towards optimizing underlying tendon healing. Tissue twitching and damage, as well as gene expression and distribution were evaluated. Bioprinted collagen scaffolds, mimicking healthy tendon structure were then implanted subcutaneously for biocompatibility and angiogenesis analyses when combined with …