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Articles 121 - 150 of 170
Full-Text Articles in Genetics and Genomics
Characterization Of Somatically-Eliminated Genes During Development Of The Sea Lamprey (Petromyzon Marinus), Stephanie A. Bryant
Characterization Of Somatically-Eliminated Genes During Development Of The Sea Lamprey (Petromyzon Marinus), Stephanie A. Bryant
Theses and Dissertations--Biology
The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during early development that facilitate the elimination of ~20% of the genome from the somatic cell lineage, resulting in distinct somatic and germline genomes. To improve our understanding of the evolutionary/developmental logic of PGR, we generated computational predictions to identify candidate germline-specific genes within a transcriptomic dataset derived from adult germline and the embryonic stages encompassing PGR. Validation studies identified 44 germline-specific genes and characterized patterns of transcription and DNA loss during early embryogenesis. Expression analyses reveal that several of these genes are differentially expressed during early embryogenesis …
Functional Significance Of Mtdna Cytosine Modification Tested By Genome Editing, Jason M. Robinson
Functional Significance Of Mtdna Cytosine Modification Tested By Genome Editing, Jason M. Robinson
Theses and Dissertations
The field of epigenetics is gaining popularity and speed, due in part to its capability to answer lingering questions about the root cause of certain diseases. Epigenetics plays a crucial role in regulation of the cell and cell survival, particularly by cytosine methylation. It remains controversial if DNMT’s which facilitate methylation are present in mammalian mitochondria and what the functional significance they may have on modification of mitochondrial DNA. CRISPR-Cas9 technology enabled genome editing to remove the MTS (mitochondrial targeting sequence) from DNMT1 of HCT116 cells, purposefully minimizing effects on nuclear cytosine methylation, while exclusively impacting mitochondrial modification. Removal of …
The First Whole Genome And Transcriptome Of The Cinereous Vulture Reveals Adaptation In The Gastric And Immune Defense Systems And Possible Convergent Evolution Between The Old And New World Vultures, Oksung Chung, Seondeok Jin, Yun Sung Cho, Jeongheui Lim, Hyunho Kim, Sungwoong Jho, Hak-Min Kim, Jehoon Jun, Hyejin Lee, Alvin Chon, Junsu Ko, Jeremy Edwards, Jessica A. Weber, Kyudong Han, Stephen J. O'Brien, Andrea Manica, Jong Bhak, Woon Kee Paek
The First Whole Genome And Transcriptome Of The Cinereous Vulture Reveals Adaptation In The Gastric And Immune Defense Systems And Possible Convergent Evolution Between The Old And New World Vultures, Oksung Chung, Seondeok Jin, Yun Sung Cho, Jeongheui Lim, Hyunho Kim, Sungwoong Jho, Hak-Min Kim, Jehoon Jun, Hyejin Lee, Alvin Chon, Junsu Ko, Jeremy Edwards, Jessica A. Weber, Kyudong Han, Stephen J. O'Brien, Andrea Manica, Jong Bhak, Woon Kee Paek
Biology Faculty Articles
Background: The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging.
Results: We sequenced the genome of a cinereous vulture, and mapped it to the bald …
An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien
An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien
Honors Scholar Theses
In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …
Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li
Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li
Dissertations and Theses (Open Access)
A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.
Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …
Addressing The Black Box Phenomenon Of Genome Sequencing And Assembly, Brandon Carter
Addressing The Black Box Phenomenon Of Genome Sequencing And Assembly, Brandon Carter
Senior Honors Projects, 2010-2019
Genomics, a study of all genetic material in an organism, is a new discipline having a great impact on medicine, agriculture, and environmental phenomena. Most undergraduate faculty members were not formally trained in genomics and must retool themselves in order to stay current with these evolving technologies. Advances in sequencing technology have resulted in an explosion of “big data” that can only be managed and analyzed using digital methods. Multiple complex computer programs are required to teach students the concepts using hands-on methods. These programs are challenging to use, especially since the same faculty members lacking genomics training were not …
Smilefinder: A Resampling-Based Approach To Evaluate Signatures Of Selection From Genome-Wide Sets Of Matching Allele Frequency Data In Two Or More Diploid Populations, Wilfred M. Guiblet, Kai Zhao, Stephen J. O'Brien, Steven E. Massey, Alfred L. Roca, T. K. Oleksyk
Smilefinder: A Resampling-Based Approach To Evaluate Signatures Of Selection From Genome-Wide Sets Of Matching Allele Frequency Data In Two Or More Diploid Populations, Wilfred M. Guiblet, Kai Zhao, Stephen J. O'Brien, Steven E. Massey, Alfred L. Roca, T. K. Oleksyk
Biology Faculty Articles
Background: Adaptive alleles may rise in frequency as a consequence of positive selection, creating a pattern of decreased variation in the neighboring loci, known as a selective sweep. When the region containing this pattern is compared to another population with no history of selection, a rise in variance of allele frequencies between populations is observed. One challenge presented by large genome-wide datasets is the ability to differentiate between patterns that are remnants of natural selection from those expected to arise at random and/or as a consequence of selectively neutral demographic forces acting in the population.
Findings: SmileFinder is …
A Comparison Of The Caulobacter Na1000 And K31 Genomes Reveals Extensive Genome Rearrangements And Differences In Metabolic Potential, Craig Stephens, Kurt Ash, Theta Brown, Tynetta Watford, Latia E. Scott, Bert Ely
A Comparison Of The Caulobacter Na1000 And K31 Genomes Reveals Extensive Genome Rearrangements And Differences In Metabolic Potential, Craig Stephens, Kurt Ash, Theta Brown, Tynetta Watford, Latia E. Scott, Bert Ely
Biology
The genus Caulobacter is found in a variety of habitats and is known for its abilityto thrive in low-nutrient conditions. K31 is a novel Caulobacter isolate that has the ability to tolerate copper and chlorophenols, and can grow at 48Cwith a doubling time of 40 h. K31 contains a 5.5 Mb chromosome that codes for more than 5500 proteins and two large plasmids (234 and 178 kb) thatcode for 438 additional proteins. A comparison of the K31 and the Caulobactercrescentus NA1000 genomes revealed extensive rearrangements of gene order,suggesting that the genomes had been randomly scrambled. However, a careful analysis revealed …
Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler
Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler
Dartmouth Scholarship
Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival.
How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos
How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos
Dartmouth Scholarship
Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …
Integrated Omics Study Delineates The Dynamics Of Lipid Droplets In Rhodococcus Opacus Pd630., Yong Chen, Yunfeng Ding, Li Yang, Jinhai Yu, Guiming Liu, Xumin Wang, Shuyan Zhang, Dan Yu, Lai Song, Hangxiao Zhang, Congyan Zhang, Linhe Huo, Chaoxing Huo, Yang Wang, Yalan Du, Huina Zhang, Peng Zhang, Huimin Na, Shimeng Xu, Yaxin Zhu, Zhensheng Xie, Tong He, Yue Zhang, Guoliang Wang, Zhonghua Fan, Fuquan Yang, Honglei Liu, Xiaowo Wang, Xuegong Zhang, Michael Q Zhang, Yanda Li, Alexander Steinbüchel, Toyoshi Fujimoto, Simon Cichello, Jun Yu, Pingsheng Liu
Integrated Omics Study Delineates The Dynamics Of Lipid Droplets In Rhodococcus Opacus Pd630., Yong Chen, Yunfeng Ding, Li Yang, Jinhai Yu, Guiming Liu, Xumin Wang, Shuyan Zhang, Dan Yu, Lai Song, Hangxiao Zhang, Congyan Zhang, Linhe Huo, Chaoxing Huo, Yang Wang, Yalan Du, Huina Zhang, Peng Zhang, Huimin Na, Shimeng Xu, Yaxin Zhu, Zhensheng Xie, Tong He, Yue Zhang, Guoliang Wang, Zhonghua Fan, Fuquan Yang, Honglei Liu, Xiaowo Wang, Xuegong Zhang, Michael Q Zhang, Yanda Li, Alexander Steinbüchel, Toyoshi Fujimoto, Simon Cichello, Jun Yu, Pingsheng Liu
College of Science & Mathematics Departmental Research
Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super …
Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams
Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams
Dartmouth Scholarship
Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …
Reflections On The Cost Of "Low-Cost" Whole Genome Sequencing: Framing The Health Policy Debate, Timothy Caulfield, Jim Evans, Amy Mcguire, Christopher Mccabe, Tania M. Bubela, Robert Cook-Deegan, Jennifer Fishman, Stuart Hogarth, Fiona A. Miller, Vardit Ravitsky
Reflections On The Cost Of "Low-Cost" Whole Genome Sequencing: Framing The Health Policy Debate, Timothy Caulfield, Jim Evans, Amy Mcguire, Christopher Mccabe, Tania M. Bubela, Robert Cook-Deegan, Jennifer Fishman, Stuart Hogarth, Fiona A. Miller, Vardit Ravitsky
Office of the Provost
The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.
Phylogenetic Portrait Of The Saccharomyces Cerevisiae Functional Genome, Patrick A. Gibney, Mark J. Hickman, Patrick H. Bradley, John C. Matese, David Botstein
Phylogenetic Portrait Of The Saccharomyces Cerevisiae Functional Genome, Patrick A. Gibney, Mark J. Hickman, Patrick H. Bradley, John C. Matese, David Botstein
College of Science & Mathematics Departmental Research
The genome of budding yeast (Saccharomyces cerevisiae) contains approximately 5800 protein-encoding genes, the majority of which are associated with some known biological function. Yet the extent of amino acid sequence conservation of these genes over all phyla has only been partially examined. Here we provide a more comprehensive overview and visualization of the conservation of yeast genes and a means for browsing and exploring the data in detail, down to the individual yeast gene, at http://yeast-phylogroups.princeton.edu. We used data from the OrthoMCL database, which has defined orthologs from approximately 150 completely sequenced genomes, including diverse representatives of …
The Genome Sequence Of The Most Widely Cultivated Cacao Type And Its Use To Identify Candidate Genes Regulating Pod Color, Juan C. Motamayor, Keithanne Mockaitis, Jeremy Schmutz, Niina Haiminen, Donald Livingstone Iii, Omar Cornejo, Seth Findley, Ping Zheng, Filippo Utro, Stefan Royaert, Christopher Saski
The Genome Sequence Of The Most Widely Cultivated Cacao Type And Its Use To Identify Candidate Genes Regulating Pod Color, Juan C. Motamayor, Keithanne Mockaitis, Jeremy Schmutz, Niina Haiminen, Donald Livingstone Iii, Omar Cornejo, Seth Findley, Ping Zheng, Filippo Utro, Stefan Royaert, Christopher Saski
Publications
Background
Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders.
Results
We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina
1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of …
Discovering Chromatin Motifs Using Faire Sequencing And The Human Diploid Genome, Chia-Chun Yang, Michael J. Buck, Min-Hsuan Chen, Yun-Fan Chen, Hsin-Chi Lan, Jeremy J.W Chen, Chao Cheng, Chun-Chi Liu
Discovering Chromatin Motifs Using Faire Sequencing And The Human Diploid Genome, Chia-Chun Yang, Michael J. Buck, Min-Hsuan Chen, Yun-Fan Chen, Hsin-Chi Lan, Jeremy J.W Chen, Chao Cheng, Chun-Chi Liu
Dartmouth Scholarship
Background: Specific chromatin structures are associated with active or inactive gene transcription. The gene regulatory elements are intrinsically dynamic and alternate between inactive and active states through the recruitment of DNA binding proteins, such as chromatin-remodeling proteins. Results: We developed a unique genome-wide method to discover DNA motifs associated with chromatin accessibility using formaldehyde-assisted isolation of regulatory elements with high-throughput sequencing (FAIRE-seq). We aligned the FAIRE-seq reads to the GM12878 diploid genome and subsequently identified differential chromatin-state regions (DCSRs) using heterozygous SNPs. The DCSR pairs represent the locations of imbalances of chromatin accessibility between alleles and are ideal to reveal …
Functional Analysis Of The Aspergillus Nidulans Kinome, Colin P. De Souza, Shahr B. Hashmi, Aysha H. Osmani, Peter Andrews, Carol S. Ringelberg, Jay C. Dunlap, Stephen A. Osmani
Functional Analysis Of The Aspergillus Nidulans Kinome, Colin P. De Souza, Shahr B. Hashmi, Aysha H. Osmani, Peter Andrews, Carol S. Ringelberg, Jay C. Dunlap, Stephen A. Osmani
Dartmouth Scholarship
The filamentous fungi are an ecologically important group of organisms which also have important industrial applications but devastating effects as pathogens and agents of food spoilage. Protein kinases have been implicated in the regulation of virtually all biological processes but how they regulate filamentous fungal specific processes is not understood. The filamentous fungus Aspergillus nidulans has long been utilized as a powerful molecular genetic system and recent technical advances have made systematic approaches to study large gene sets possible. To enhance A. nidulans functional genomics we have created gene deletion constructs for 9851 genes representing 93.3% of the encoding genome. …
Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy
Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy
Manuscripts, Articles, Book Chapters and Other Papers
The era of "Personalized Medicine," guided by individual molecular variation in DNA, RNA, expressed proteins and other forms of high volume molecular data brings new requirements and challenges to the design and implementation of Electronic Health Records (EHRs). In this article we describe the characteristics of biomolecular data that differentiate it from other classes of data commonly found in EHRs, enumerate a set of technical desiderata for its management in healthcare settings, and offer a candidate technical approach to its compact and efficient representation in operational systems.
Genome-Wide Expression Analysis In Down Syndrome: Insight Into Immunodeficiency, Chong Li, Lei Jin, Yun Bai, Qimin Chen, Lijun Fu, Minjun Yang, Huasheng Xiao, Guoping Zhao, Shengyue Wang
Genome-Wide Expression Analysis In Down Syndrome: Insight Into Immunodeficiency, Chong Li, Lei Jin, Yun Bai, Qimin Chen, Lijun Fu, Minjun Yang, Huasheng Xiao, Guoping Zhao, Shengyue Wang
PCOM Scholarly Works
Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group …
Adventures In The Enormous: A 1.8 Million Clone Bac Library For The 21.7 Gb Genome Of Loblolly Pine., Zenaida V. Magbanua, Seval Ozkan, Benjamin D. Bartlett, Philippe Chouvarine, Christopher A. Saski, Aaron Liston, Richard C. Cronn, C. Dana Nelson, Daniel G. Peterson
Adventures In The Enormous: A 1.8 Million Clone Bac Library For The 21.7 Gb Genome Of Loblolly Pine., Zenaida V. Magbanua, Seval Ozkan, Benjamin D. Bartlett, Philippe Chouvarine, Christopher A. Saski, Aaron Liston, Richard C. Cronn, C. Dana Nelson, Daniel G. Peterson
CALS Publications
Loblolly pine (LP; Pinus taeda L.) is the most economically important tree in the U.S. and a cornerstone species in southeastern forests. However, genomics research on LP and other conifers has lagged behind studies on flowering plants due, in part, to the large size of conifer genomes. As a means to accelerate conifer genome research, we constructed a BAC library for the LP genotype 7-56. The LP BAC library consists of 1,824,768 individually-archived clones making it the largest single BAC library constructed to date, has a mean insert size of 96 kb, and affords 7.6X coverage of the 21.7 Gb …
Micrornas Reveal The Interrelationships Of Hagfish, Lampreys, And Gnathostomes And The Nature Of The Ancestral Vertebrate, Alysha M. Heimberg, Richard Cowper-Sal{Middle Dot}Lari, Marie Semon, Philip C. J. Donoghue, Kevin J. Peterson
Micrornas Reveal The Interrelationships Of Hagfish, Lampreys, And Gnathostomes And The Nature Of The Ancestral Vertebrate, Alysha M. Heimberg, Richard Cowper-Sal{Middle Dot}Lari, Marie Semon, Philip C. J. Donoghue, Kevin J. Peterson
Dartmouth Scholarship
Hagfish and lampreys are the only living representatives of the jawless vertebrates (agnathans), and compared with jawed vertebrates (gnathostomes), they provide insight into the embryology, genomics, and body plan of the ancestral vertebrate. However, this insight has been obscured by controversy over their interrelationships. Morphological cladistic analyses have identified lampreys and gnathostomes as closest relatives, whereas molecular phylogenetic studies recover a monophyletic Cyclostomata (hagfish and lampreys as closest relatives). Here, we show through deep sequencing of small RNA libraries, coupled with genomic surveys, that Cyclostomata is monophyletic: hagfish and lampreys share 4 unique microRNA families, 15 unique paralogues of more …
Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate
Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate
Microbiology, Immunology, and Molecular Genetics Faculty Publications
The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …
Error Correcting Codes And The Human Genome., Suzanne Mclean Lyle
Error Correcting Codes And The Human Genome., Suzanne Mclean Lyle
Electronic Theses and Dissertations
In this work, we study error correcting codes and generalize the concepts with a view toward a novel application in the study of DNA sequences. The author investigates the possibility that an error correcting linear code could be included in the human genome through application and research. The author finds that while it is an accepted hypothesis that it is reasonable that some kind of error correcting code is used in DNA, no one has actually been able to identify one. The author uses the application to illustrate how the subject of coding theory can provide a teaching enrichment activity …
Genomic Perspectives On Evolution In Bracken Fern, Joshua P. Der
Genomic Perspectives On Evolution In Bracken Fern, Joshua P. Der
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
The fern genus Pteridium comprises a number of closely related species distributed throughout the world. Collectively they are called bracken ferns and have historically been treated as a single species, Pteridium aquilinum. Bracken is notorious as a toxic weed that colonizes open fields and poisons livestock. Bracken is also easily cultured and has become one of the most intensively studied ferns. Bracken has been used as a model system for the study of the fern life cycle, fern gametophyte development, the pheromonal mechanism of sex determination, toxicology, invasion ecology, and climate change. This dissertation places bracken within a global …
Genome3d: A Viewer-Model Framework For Integrating And Visualizing Multi-Scale Epigenomic Information Within A Three-Dimensional Genome, Thomas M. Asbury, Matt Mitman, Jijun Tang, W. Jim Zheng
Genome3d: A Viewer-Model Framework For Integrating And Visualizing Multi-Scale Epigenomic Information Within A Three-Dimensional Genome, Thomas M. Asbury, Matt Mitman, Jijun Tang, W. Jim Zheng
Faculty Publications
Background
New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation.
Results
We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order …
Microbial Nad Metabolism: Lessons From Comparative Genomics, Francesca Gazzaniga, Rebecca Stebbins, Sheila Z. Chang, Mark A. Mcpeek, Charles Brenner
Microbial Nad Metabolism: Lessons From Comparative Genomics, Francesca Gazzaniga, Rebecca Stebbins, Sheila Z. Chang, Mark A. Mcpeek, Charles Brenner
Dartmouth Scholarship
NAD is a coenzyme for redox reactions and a substrate of NAD-consuming enzymes, including ADP-ribose transferases, Sir2-related protein lysine deacetylases, and bacterial DNA ligases. Microorganisms that synthesize NAD from as few as one to as many as five of the six identified biosynthetic precursors have been identified. De novo NAD synthesis from aspartate or tryptophan is neither universal nor strictly aerobic. Salvage NAD synthesis from nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinic acid riboside occurs via modules of different genes. Nicotinamide salvage genes nadV and pncA, found in distinct bacteria, appear to have spread throughout the tree of life …
Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore
Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore
Dartmouth Scholarship
Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To …
Correcting The Site Frequency Spectrum For Divergence-Based Ascertainment, Andrew D. Kern
Correcting The Site Frequency Spectrum For Divergence-Based Ascertainment, Andrew D. Kern
Dartmouth Scholarship
Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions …
Evolution Of Genome Size And Complexity In Pinus., Alison M. Morse, Daniel G. Peterson, M. Nurul Islam-Faridi, Katherine E. Smith, Zenaida V. Magbanua, Saul A. Garcia, Thomas L. Kubisiak, Henry V. Amerson, John E. Carlson, C. Dana Nelson, John M. Davis
Evolution Of Genome Size And Complexity In Pinus., Alison M. Morse, Daniel G. Peterson, M. Nurul Islam-Faridi, Katherine E. Smith, Zenaida V. Magbanua, Saul A. Garcia, Thomas L. Kubisiak, Henry V. Amerson, John E. Carlson, C. Dana Nelson, John M. Davis
CALS Publications
BACKGROUND: Genome evolution in the gymnosperm lineage of seed plants has given rise to many of the most complex and largest plant genomes, however the elements involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Gymny is a previously undescribed retrotransposon family in Pinus that is related to Athila elements in Arabidopsis. Gymny elements are dispersed throughout the modern Pinus genome and occupy a physical space at least the size of the Arabidopsis thaliana genome. In contrast to previously described retroelements in Pinus, the Gymny family was amplified or introduced after the divergence of pine and spruce (Picea). If retrotransposon expansions are responsible …
Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss
Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss
Biology Faculty Publications
BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.
RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …