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Articles 121 - 150 of 616
Full-Text Articles in Genetics and Genomics
Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic
Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic
Epidemiology and Environmental Health Faculty Publications
Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.
Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).
Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.
Results: We observed significant methylation differences in …
Red Fox Genome Assembly Identifies Genomic Regions Associated With Tame And Aggressive Behaviours, Anna V. Kukekova, Jennifer L. Johnson, Xueyan Xiang, Shaohong Feng, Shiping Liu, Halie M. Rando, Anastasiya V. Kharlamova, Yury Herbeck, Natalya A. Serdyukova, Zijun Xiong, Violetta Beklemischeva, Klaus Peter Koepfli, Rimma G. Gulevich, Anastasiya V. Vladimirova, Jessica P. Hekman, Polina L. Perelman, Aleksander S. Graphodatsky, Stephen J. O’Brien, Xu Wang, Andrew G. Clark, Gregory M. Acland, Lyudmila N. Trut, Guojie Zhang
Red Fox Genome Assembly Identifies Genomic Regions Associated With Tame And Aggressive Behaviours, Anna V. Kukekova, Jennifer L. Johnson, Xueyan Xiang, Shaohong Feng, Shiping Liu, Halie M. Rando, Anastasiya V. Kharlamova, Yury Herbeck, Natalya A. Serdyukova, Zijun Xiong, Violetta Beklemischeva, Klaus Peter Koepfli, Rimma G. Gulevich, Anastasiya V. Vladimirova, Jessica P. Hekman, Polina L. Perelman, Aleksander S. Graphodatsky, Stephen J. O’Brien, Xu Wang, Andrew G. Clark, Gregory M. Acland, Lyudmila N. Trut, Guojie Zhang
Biology Faculty Articles
Strains of red fox (Vulpes vulpes) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment. Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations. A strong positional candidate gene for tame behaviour was highlighted: SorCS1, which encodes …
Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark
Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark
Dissertations, Theses, and Capstone Projects
The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …
Confirming World-Wide Distribution Of An Agriculturally Important Lacewing, Chrysoperla Zastrowi Sillemi, Using Songs, Morphology, Mitochondrial Gene Sequencing, And Phylogenetic Reconstruction, Zoe Mandese
Honors Scholar Theses
The Chrysoperla carnea-group of green lacewings is a cryptic species complex. Species within the group are morphologically similar, yet isolated from one another via reproductive mating song. Chrysoperla zastrowi, a species within the carnea-group, is currently described with a distribution ranging from South Africa to the Middle East and India. However, recent collections of carnea-group lacewings from Guatemala and California were preliminarily identified as Chrysoperla zastrowi based upon similarities in their vibrational courtship songs. This analysis aims to place six specimens, collected by collaborators in Guatemala, Armenia, Iran, and California, into a pre-existing phylogeny of the …
Aspen Recruitment In The Yellowstone Region Linked To Reduced Herbivory After Large Carnivore Restoration, Luke E. Painter, Robert L. Beschta, Eric J. Larsen, William J. Ripple
Aspen Recruitment In The Yellowstone Region Linked To Reduced Herbivory After Large Carnivore Restoration, Luke E. Painter, Robert L. Beschta, Eric J. Larsen, William J. Ripple
Aspen Bibliography
Quaking aspen (Populus tremuloides) recruitment during the 1980s–90s was suppressed by Rocky Mountain elk (Cervus canadensis) herbivory on winter ranges in the Yellowstone region, and saplings (young aspen taller than 2 m) were rare. Following the 1995–96 reintroduction of gray wolves (Canis lupus), browsing decreased and sapling recruitment increased in Yellowstone National Park. We compared aspen data from inside the park to data collected in three winter ranges outside the park. For most areas, the percentage of young aspen browsed annually was 80–100% in 1997–98, decreasing to 30–60% in 2011–15. Sapling recruitment was inversely …
Effects Of Stand Structure, Browsing, And Biophysical Conditions On Regeneration Following Mountain Pine Beetle In Mixed Lodgepole Pine And Aspen Forests Of The Southern Rockies, Kristen A. Pelz, Frederick W. Smith
Effects Of Stand Structure, Browsing, And Biophysical Conditions On Regeneration Following Mountain Pine Beetle In Mixed Lodgepole Pine And Aspen Forests Of The Southern Rockies, Kristen A. Pelz, Frederick W. Smith
Aspen Bibliography
Aspen (Populus tremuloides) and lodgepole pine (Pinus contorta var. latifolia) co-occur in the southern Rocky Mountains (USA), where mountain pine beetle (MPB, Dendroctonus ponderosae) has caused extensive lodgepole pine mortality since the late 1990s. Both species excel in post-disturbance high-light environments, but lodgepole pine has generally been thought to establish poorly on undisturbed seedbeds, and aspen suckering may be inhibited by intact aspen overstory. We ask whether lodgepole pine and aspen will regenerate in sufficient quantities to revegetate these forests. We visited a random sample of aspen and lodgepole pine stands across the affected landscape …
Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson
Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …
Characterization Of Mrna Polyadenylation In The Apicomplexa, Ashley T. Stevens, Daniel K. Howe, Arthur G. Hunt
Characterization Of Mrna Polyadenylation In The Apicomplexa, Ashley T. Stevens, Daniel K. Howe, Arthur G. Hunt
Plant and Soil Sciences Faculty Publications
Messenger RNA polyadenylation is a universal aspect of gene expression in eukaryotes. In well-established model organisms, this process is mediated by a conserved complex of 15–20 subunits. To better understand this process in apicomplexans, a group of unicellular parasites that causes serious disease in humans and livestock, a computational and high throughput sequencing study of the polyadenylation complex and poly(A) sites in several species was conducted. BLAST-based searches for orthologs of the human polyadenylation complex yielded clear matches to only two—poly(A) polymerase and CPSF73—of the 19 proteins used as queries in this analysis. As the human subunits that recognize the …
Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer
Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer
College of Science & Mathematics Departmental Research
Viral gain‐of‐function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …
Regulated Capture Of Vκ Gene Topologically Associating Domains By Transcription Factories, Sophiya Karki, Domenick E. Kennedy, Kaitlin Mclean, Adrian T. Grzybowski, Mark Maienschein-Cline, Shiladitya Banerjee, Heping Xu, Elizabeth Davis, Malay Mandal, Christine Labno, Sarah E. Powers, Michelle M. Le Beau, Aaron R. Dinner, Harinder Singh, Alexander J. Ruthenburg, Marcus R. Clark
Regulated Capture Of Vκ Gene Topologically Associating Domains By Transcription Factories, Sophiya Karki, Domenick E. Kennedy, Kaitlin Mclean, Adrian T. Grzybowski, Mark Maienschein-Cline, Shiladitya Banerjee, Heping Xu, Elizabeth Davis, Malay Mandal, Christine Labno, Sarah E. Powers, Michelle M. Le Beau, Aaron R. Dinner, Harinder Singh, Alexander J. Ruthenburg, Marcus R. Clark
Biology Department Faculty Articles
Expression of vast repertoires of antigen receptors by lymphocytes, with each cell expressing a single receptor, requires stochastic activation of individual variable (V) genes for transcription and recombination. How this occurs remains unknown. Using single-cell RNA sequencing (scRNA-seq) and allelic variation, we show that individual pre-B cells monoallelically transcribe divergent arrays of Vκ genes, thereby opening stochastic repertoires for subsequent Vκ-Jκ recombination. Transcription occurs upon translocation of Vκ genes to RNA polymerase II arrayed on the nuclear matrix in transcription factories. Transcription is anchored by CTCF-bound sites or E2A-loaded Vκ promotors and continues over large genomic distances delimited only by …
Genome-Wide Association Study For Variants That Modulate Relationships Between Cerebrospinal Fluid Amyloid-Beta 42, Tau, And P-Tau Levels, Taylor J. Maxwell, Chris Corcoran, Jorge L. Del-Aguila, John P. Budde, Yuetiva Deming, Carlos Cruchaga, Alison M. Goate, John S. K. Kauwe, Alzheimer's Disease Neuroimaging Initiative
Genome-Wide Association Study For Variants That Modulate Relationships Between Cerebrospinal Fluid Amyloid-Beta 42, Tau, And P-Tau Levels, Taylor J. Maxwell, Chris Corcoran, Jorge L. Del-Aguila, John P. Budde, Yuetiva Deming, Carlos Cruchaga, Alison M. Goate, John S. K. Kauwe, Alzheimer's Disease Neuroimaging Initiative
Mathematics and Statistics Faculty Publications
Background: A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G.
Methods: We performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping …
Ubiquitin Regulation: The Histone Modifying Enzyme's Story, Jianlin Wang, Zhaoping Qiu, Yadi Wu
Ubiquitin Regulation: The Histone Modifying Enzyme's Story, Jianlin Wang, Zhaoping Qiu, Yadi Wu
Pharmacology and Nutritional Sciences Faculty Publications
Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes.
Mobile Elements Shape Plastome Evolution In Ferns, Tanner A. Robison, Amanda L. Grusz, Paul G. Wolf, Jeffrey P. Mower, Blake D. Fauskee, Karla Sosa, Eric Schuettpelz
Mobile Elements Shape Plastome Evolution In Ferns, Tanner A. Robison, Amanda L. Grusz, Paul G. Wolf, Jeffrey P. Mower, Blake D. Fauskee, Karla Sosa, Eric Schuettpelz
Biology Faculty Publications
Plastid genomes display remarkable organizational stability over evolutionary time. From green algae to angiosperms, most plastid genomes are largely collinear, with only a few cases of inversion, gene loss, or, in extremely rare cases, gene addition. These plastome insertions are mostly clade-specific and are typically of nuclear or mitochondrial origin. Here, we expand on these findings and present the first family-level survey of plastome evolution in ferns, revealing a novel suite of dynamic mobile elements. Comparative plastome analyses of the Pteridaceae expose several mobile open reading frames that vary in sequence length, insertion site, and configuration among sampled taxa. Even …
Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt
Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt
Human Biology Open Access Pre-Prints
Computed tomography (CT) scans provide anthropologists with a resource to generate three- dimensional (3D) digital skeletal material to expand quantification methods and build more standardized reference collections. The ability to visualize and manipulate the bone and skin of the face simultaneously in a 3D digital environment introduces a new way for forensic facial approximation practitioners to access and study the face. Craniofacial relationships can be quantified with landmarks or with surface processing software that can quantify the geometric properties of the entire 3D facial surface. This paper describes tools for the generation of dense facial tissue depth maps (FTDMs) using …
Of Typicality And Predictive Distributions In Discriminant Function Analysis, Lyle W. Konigsberg, Susan R. Frankenberg
Of Typicality And Predictive Distributions In Discriminant Function Analysis, Lyle W. Konigsberg, Susan R. Frankenberg
Human Biology Open Access Pre-Prints
While discriminant function analysis is an inherently Bayesian method, researchers attempting to estimate ancestry in human skeletal samples often follow discriminant function analysis with the calculation of frequentist-based typicalities for assigning group membership. Such an approach is problematic in that it fails to account for admixture and for variation in why individuals may be classified as outliers, or non-members of particular groups. This paper presents an argument and methodology for employing a fully Bayesian approach in discriminant function analysis applied to cases of ancestry estimation. The approach requires adding the calculation, or estimation, of predictive distributions as the final step …
Transcriptional Response Of Honey Bee (Apis Mellifera) To Differential Nutritional Status And Nosema Infection, Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman
Transcriptional Response Of Honey Bee (Apis Mellifera) To Differential Nutritional Status And Nosema Infection, Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman
Plant and Soil Sciences Faculty Publications
Background: Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice, however, commercial substitutes, such as Bee-Pro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism.
Results: Gene ontology enrichment revealed that, compared with poor diet (carbohydrates [C]), bees fed pollen (P > C), Bee-Pro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions, and …
N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers
N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers
Rowan-Virtua School of Osteopathic Medicine Departmental Research
The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …
Double-Stranded Rna Binding Protein, Staufen, Is Required For The Initiation Of Rnai In Coleopteran Insects, June-Sun Yoon, Kanakachari Mogilicherla, Dhandapani Gurusamy, Xien Chen, Shankar C. R. R. Chereddy, Subba R. Palli
Double-Stranded Rna Binding Protein, Staufen, Is Required For The Initiation Of Rnai In Coleopteran Insects, June-Sun Yoon, Kanakachari Mogilicherla, Dhandapani Gurusamy, Xien Chen, Shankar C. R. R. Chereddy, Subba R. Palli
Entomology Faculty Publications
RNA interference (RNAi) is being used to develop methods to control pests and disease vectors. RNAi is robust and systemic in coleopteran insects but is quite variable in other insects. The determinants of efficient RNAi in coleopterans, as well as its potential mechanisms of resistance, are not known. RNAi screen identified a double-stranded RNA binding protein (StaufenC) as a major player in RNAi. StaufenC homologs have been identified in only coleopteran insects. Experiments in two coleopteran insects, Leptinotarsa decemlineata and Tribolium castaneum, showed the requirement of StaufenC for RNAi, especially for processing of double-stranded RNA (dsRNA) to small interfering …
Work-Type Influences Perceived Livestock Herding Success In Australian Working Kelpies, Jonathan B. Early, Elizabeth R. Arnott, Lisa J. Mascord, Diane Van Rooy, Paul Mcgreevy, Claire M. Wade
Work-Type Influences Perceived Livestock Herding Success In Australian Working Kelpies, Jonathan B. Early, Elizabeth R. Arnott, Lisa J. Mascord, Diane Van Rooy, Paul Mcgreevy, Claire M. Wade
Genetics Collection
Background
Working dog handlers and breeders have very different behavioural requirements in the animals that they employ for managing livestock. The Australian Working Kelpie breed may be used in several working contexts, notably yards, paddocks and a combination of both. The working context influences the skillsets required and gives rise to three corresponding work-types: Yard, Paddock and Utility Kelpies. In particular, dogs used for working stock in the confines of yards and trucks interact with stock more forcefully than those mustering in larger areas (paddocks) where they can herd stock effectively from a greater distance. This article explores owner assessments …
Provenance And Risk In Transfer Of Biological Materials, Jane Nielsen, Tania M. Bubela, Don R C. Chalmers, Amber Johns, Linda Kahl, Joanne Kamens, Charles Lawson, John Liddicoat, Rebekah Mcwhirter, Ann Monott
Provenance And Risk In Transfer Of Biological Materials, Jane Nielsen, Tania M. Bubela, Don R C. Chalmers, Amber Johns, Linda Kahl, Joanne Kamens, Charles Lawson, John Liddicoat, Rebekah Mcwhirter, Ann Monott
Office of the Provost
Whereas biological materials were once transferred freely, there has been a marked shift in the formalisation of exchanges involving these materials, primarily through the use of Material Transfer Agreements (MTAs). This paper considers how risk aversion dominates MTA negotiations and the impact it may have on scientific progress. Risk aversion is often based on unwarranted fears of incurring liability through the use of a material or loss of control or missing out on commercialisation opportunities. Evidence to date has suggested that complexity tends to permeate even straightforward transactions despite extensive efforts to implement simple, standard MTAs. We argue that in …
Determining Relative Dynamic Stability Of Cell States Using Boolean Network Model., Jae Il Joo, Joseph X Zhou, Sui Huang, Kwang-Hyun Cho
Determining Relative Dynamic Stability Of Cell States Using Boolean Network Model., Jae Il Joo, Joseph X Zhou, Sui Huang, Kwang-Hyun Cho
Articles, Abstracts, and Reports
Cell state transition is at the core of biological processes in metazoan, which includes cell differentiation, epithelial-to-mesenchymal transition (EMT) and cell reprogramming. In these cases, it is important to understand the molecular mechanism of cellular stability and how the transitions happen between different cell states, which is controlled by a gene regulatory network (GRN) hard-wired in the genome. Here we use Boolean modeling of GRN to study the cell state transition of EMT and systematically compare four available methods to calculate the cellular stability of three cell states in EMT in both normal and genetically mutated cases. The results produced …
Bioinformatic Analysis Of Endogenous And Exogenous Small Rnas On Lipoproteins, Ryan M. Allen, Shilin Zhao, Marisol A. Ramirez Solano, Wanying Zhu, Danielle L. Michell, Yuhuan Wang, Yu Shyr, Praveen Sethupathy, Macrae F. Linton, Gregory A. Graf, Quanhu Sheng, Kasey C. Vickers
Bioinformatic Analysis Of Endogenous And Exogenous Small Rnas On Lipoproteins, Ryan M. Allen, Shilin Zhao, Marisol A. Ramirez Solano, Wanying Zhu, Danielle L. Michell, Yuhuan Wang, Yu Shyr, Praveen Sethupathy, Macrae F. Linton, Gregory A. Graf, Quanhu Sheng, Kasey C. Vickers
Pharmaceutical Sciences Faculty Publications
To comprehensively study extracellular small RNAs (sRNA) by sequencing (sRNA-seq), we developed a novel pipeline to overcome current limitations in analysis entitled, “Tools for Integrative Genome analysis of Extracellular sRNAs (TIGER)”. To demonstrate the power of this tool, sRNA-seq was performed on mouse lipoproteins, bile, urine and livers. A key advance for the TIGER pipeline is the ability to analyse both host and non-host sRNAs at genomic, parent RNA and individual fragment levels. TIGER was able to identify approximately 60% of sRNAs on lipoproteins and >85% of sRNAs in liver, bile and urine, a significant advance compared to existing software. …
Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold
Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold
Markey Cancer Center Faculty Publications
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …
Role Of Nucleotide Identity In Effective Crispr Target Escape Mutations, Tim Künne, Yifan Zhu, Fausia Da Silva, Nico Konstantinides, Rebecca E. Mckenzie, Ryan N. Jackson, Stan J.J. Brouns
Role Of Nucleotide Identity In Effective Crispr Target Escape Mutations, Tim Künne, Yifan Zhu, Fausia Da Silva, Nico Konstantinides, Rebecca E. Mckenzie, Ryan N. Jackson, Stan J.J. Brouns
Chemistry and Biochemistry Faculty Publications
Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly influence the efficiency of primed CRISPR adaptation. Here we show that guanine-substitutions in the target strand of the protospacer are highly detrimental to CRISPR interference and interference-dependent priming, while cytosine-substitutions are more readily tolerated. Furthermore, we show that this effect is based on strongly decreased binding affinity of the effector complex Cascade for guanine-mismatched targets, while cytosine-mismatched targets …
Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. C. Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler
Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. C. Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler
Bioinformatics Faculty Publications
For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. …
Imapsplice: Alleviating Reference Bias Through Personalized Rna-Seq Alignment, Xinan Liu, James N. Macleod, Jinze Liu
Imapsplice: Alleviating Reference Bias Through Personalized Rna-Seq Alignment, Xinan Liu, James N. Macleod, Jinze Liu
Computer Science Faculty Publications
Genomic variants in both coding and non-coding sequences can have functionally important and sometimes deleterious effects on exon splicing of gene transcripts. For transcriptome profiling using RNA-seq, the accurate alignment of reads across exon junctions is a critical step. Existing algorithms that utilize a standard reference genome as a template sometimes have difficulty in mapping reads that carry genomic variants. These problems can lead to allelic ratio biases and the failure to detect splice variants created by splice site polymorphisms. To improve RNA-seq read alignment, we have developed a novel approach called iMapSplice that enables personalized mRNA transcriptome profiling. The …
Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. Craig Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler
Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. Craig Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler
Biology: Faculty Publications and Other Works
For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. …
An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen
An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen
Faculty, Staff and Students Publications
We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …
The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall
The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall
Publications and Research
The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. …
A Tissue-Based Draft Map Of The Murine Mhc Class I Immunopeptidome., Heiko Schuster, Wenguang Shao, Tobias Weiss, Patrick G A Pedrioli, Patrick Roth, Michael Weller, David S Campbell, Eric W Deutsch, Robert L Moritz, Oliver Planz, Hans-Georg Rammensee, Ruedi Aebersold, Etienne Caron
A Tissue-Based Draft Map Of The Murine Mhc Class I Immunopeptidome., Heiko Schuster, Wenguang Shao, Tobias Weiss, Patrick G A Pedrioli, Patrick Roth, Michael Weller, David S Campbell, Eric W Deutsch, Robert L Moritz, Oliver Planz, Hans-Georg Rammensee, Ruedi Aebersold, Etienne Caron
Articles, Abstracts, and Reports
The large array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC class I immunopeptidome. Although the MHC class I immunopeptidome is ubiquitous in mammals and represents a critical component of the immune system, very little is known, in any species, about its composition across most tissues and organs in vivo. We applied mass spectrometry (MS) technologies to draft the first tissue-based atlas of the murine MHC class I immunopeptidome in health. Peptides were extracted from 19 normal tissues from C57BL/6 mice and prepared for MS injections, resulting …