Genomics Commons^™

Steps In Metagenomics: Let’S Avoid Garbage In And Garbage Out, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Is metagenomics a revolution or a new fad? Metagenomics is tightly associated with the availability of next-generation sequencing in all its implementations. The key feature of these new technologies, moving beyond the Sanger-based DNA sequencing approach, is the depth of nucleotide sequencing per sample.Knowing much more about a sample changes the traditional paradigms of “What is the most abundant?” or “What is the most significant?” to “What is present and potentially sig­nificant that might influence the situation and outcome?” Let’s take the case of identifying proper biomarkers of disease state in the context of chronic disease prevention. Prevention has been …

Hash-Map-Eradicator: Filtering Non-Target Sequences From Next Generation Sequencing Reads, Jonathon Brenner, Catherine Putonti

Bioinformatics Faculty Publications

Contemporary DNA sequencing technologies are continuously increasing throughput at ever decreasing costs. Moreover, due to recent advances in sequencing technology new platforms are emerging. As such computational challenges persist. The average read length possible has taken a giant leap forward with the PacBio and Nanopore solutions. Regardless of the platform used, impurities within the DNA preparation of the sample - be it from unintentional contaminants or pervasive symbiots - remains an issue. We have developed a new tool, HAsh-MaP-ERadicator (HAMPER), for the detection and removal of non-target, contaminating DNA sequences. Integrating hash-based and mapping-based strategies, HAMPER is both memory and …

Investigating The Role Of The Nucleosome Remodeling Factor Nurf As A Regulator Of Gene Expression, Aiman S. Alhazmi

Theses and Dissertations

The nucleosome remodeling factor (NURF) is an evolutionary conserved ATP-dependent chromatin remodeling factor. It was first isolated from Drosophila as a complex with enzymatic activity that once recruited to nucleosome, it slides the nucleosome to provide accessibility for transcription factors. Since then, numerous works from animal models and cell lines show the role of NURF as a regulator of gene expression. NURF interacts with H3K4me3 and sequence specific transcription factors that recruit the complex to promoter regions. Whether this is the only mechanism by which NURF regulates gene expression is not known. However, other ATP-dependent chromatin remodeling complexes are known …

Drosophila Muller F Elements Maintain A Distinct Set Of Genomic Properties Over 40 Million Years Of Evolution, Wilson Leung, Christopher D. Shaffer, Laura K. Reed, Sheryl T. Smith, Randall J. Dejong, Arlene J. Hoogewerf

University Faculty Publications and Creative Works

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have …

The Genetic Ancestry Of African Americans, Latinos, And European Americans Across The United States, Katarzyna Bryc, Eric Y. Durand, J. Michael Macpherson, David Reich, Joanna Mountain

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical …

Comparative Genome Analyses Reveal Distinct Structure In The Saltwater Crocodile Mhc., Weerachai Jaratlerdsiri, Janine Deakin, Ricardo M. Godinez, Xueyan Shan, Daniel G. Peterson, Sylvain Marthey, Eric Lyons, Fiona M. Mccarthy, Sally R. Isberg, Damien P. Higgins, Amanda Y. Chong, John St. John, Travis C. Glenn, David A. Ray, Jaime Gongora

CALS Publications

The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters …

The Unseen World: Environmental Microbial Sequencing And Identification Methods For Ecologists, Naupaka Zimmerman, Jacques Izard, Christian Klatt, Jizhong Zhou, Emma Aronson

Department of Food Science and Technology: Faculty Publications

Archaea, bacteria, microeukaryotes, and the viruses that infect them (collectively “microorganisms”) are foundational components of all ecosystems, inhabiting almost every imaginable environment and comprising the majority of the planet’s organismal and evolutionary diversity. Microorganisms play integral roles in ecosystem functioning; are important in the biogeochemical cycling of carbon (C), nitrogen (N), sulfur (S), phosphorus (P), and various metals (eg Barnard et al. 2005); and may be vital to ecosystem responses to large-scale climatic change. Rarely found alone, microorganisms often form complex communities that are dynamic in space and time. For these and other reasons, ecologists and environmental scientists have become …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Comparative Genomics Reveals Insights Into Avian Genome Evolution And Adaptation, Guojie Zhang, Cai Li, Qiye Li, Bo Li, Dennis M. Larkin, Chul Lee, Jay F. Storz, Agostinho Antunes, Matthew J. Greenwold, Robert W. Meredith, Anders Ödeen, Jie Cui, Qi Zhou, Luohao Xu, Hailin Pan, Zongji Wang, Lijun Jin, Pei Zhang, Haofu Hu, Wei Yang, Jiang Hu, Jin Xiao, Zhikai Yang, Yang Liu, Qiaolin Xie, Hao Yu, Jinmin Lian, Ping Wen, Fang Zhang, Hui Li, Yongli Zeng, Zijun Xiong, Shiping Liu, Long Zhou, Zhiyong Huang, Na An, Jie Wang, Quimei Zheng, Yingqi Xiong, Guangbiao Wang, Bo Wang, Jingjing Wang, Yu Fan, Rute R. Da Fonseca, Alonzo Alfaro-Núñez, Mikkel Schubert, Ludovic Orlando, Tobias Mourier, Jason T. Howard, Ganeshkumar Ganapathy, Andreas Pfenning, Osceola Whitney, Miriam V. Rivas, Erina Hara, Julia Smith, Marta Farré, Jitendra Narayan, Gancho Slavov, Michael N. Romanov, Rui Borges, João Paulo Machado, Imran Khan, Mark S. Springer, John Gatesy, Federico G. Hoffmann, Juan C. Opazo, Olle Håstad, Roger H. Sawyer, Heebal Kim, Kyu-Won Kim, Hyeon Jeong Kim, Seoae Cho, Ning Li, Yinhua Huang, Michael W. Bruford, Xiangjiang Zhan, Andrew Dixon, Mads F. Bertelsen, Elizabeth Derryberry, Wesley Warren, Richard K. Wilson, Shengbin Li, David A. Ray, Richard E. Green, Stephen J. O'Brien, Darren Griffin, Warren E. Johnson, David Haussler, Oliver A. Ryder, Eske Willerslev, Gary R. Graves, Per Alström, Jon Fjeldså, David P. Mindell, Scott V. Edwards, Edward L. Braun, Carsten Rahbek, David W. Burt, Peter Houde, Yong Zhang, Huanming Yang, Jian Wang, Avian Genome Consortium, Erich D. Jarvis, M. Thomas P. Gilbert, Jun Wang

Jay F. Storz Publications

Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses …

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 …

Draft Genome Sequences Of Antibiotic-Resistant Commensal Escherichia Coli, Meghan Garrett, Jennifer Parker, Craig M. Stephens

Biology

Antimicrobial resistance is a significant public health issue. We report here the draft genome sequences of three drug-resistant strains of commensal Escherichia coli isolated from a single healthy college student. Each strain has a distinct genome, but two of the three contain an identical large plasmid with multiple resistance genes.

Characterization Of The Transcriptome, Nucleotide Sequence Polymorphism, And Natural Selection In The Desert Adapted Mouse Peromyscus Eremicus, Matthew D. Macmanes, Michael B. Eisen

Molecular, Cellular & Biomedical Sciences

As a direct result of intense heat and aridity, deserts are thought to be among the most harsh of environments, particularly for their mammalian inhabitants. Given that osmoregulation can be challenging for these animals, with failure resulting in death, strong selection should be observed on genes related to the maintenance of water and solute balance. One such animal, Peromyscus eremicus, is native to the desert regions of the southwest United States and may live its entire life without oral fluid intake. As a first step toward understanding the genetics that underlie this phenotype, we present a characterization of the …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Advancing The Microbiome Research Community, Curtis Huttenhower, Rob Knight, C. Titus Brown, J. Gregory Caporaso, Jose C. Clemente, Dirk Gevers, Eric A. Franzosa, Scott T. Kelley, Dan Knights, Ruth E. Ley, Anup Mahurkar, Jacques Ravel, Scientists For Advancement Of Microbiome Research, Owen White, Jacques Izard

Department of Food Science and Technology: Faculty Publications

The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology.

It is now widely recognized that disturbances in our normal microbial populations may be linked to acute infections such as Clostridium difficile and to chronic diseases such as heart disease, cancer, obesity, and autoimmune disorders. This has prompted substantial interest in the microbiome from both basic and clinical perspectives. …

Mapping Regions Of Rnf168 Required For Its Degradation By Icp0, Andrea Cyr, Matthew Weitzman

e-Research: A Journal of Undergraduate Work

Viruses establish infection by overtaking host cell processes and developing mechanisms that promote viral replication. Herpes simplex virus undergoes lytic and latent cycles of infection throughout the lifespan of its host. The viral genome is transcriptionally silent during latency, but viral proteins are produced upon reactivation. Herpes simplex virus type 1 encodes the ICP0 protein, an E3 ubiquitin ligase required for reactivation from latency of the infectious virus. The immediate-early protein ICP0 regulates the herpes simplex virus by activating viral gene expression thereby initiating lytic infection. Cellular proteins are degraded by ICP0, promoting the virus to enter the lytic cycle. …

Mammalian Keratin Associated Proteins (Krtaps) Subgenomes: Disentangling Hair Diversity And Adaptation To Terrestrial And Aquatic Environments, Imran Khan, Emanuel Maldonado, Vitor Vasconcelos, Stephen J. O'Brien, Warren E. Johnson, Agostinho Antunes

Marine & Environmental Sciences Faculty Articles

Background: Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.

Results: We exhaustively characterized the KRTAP gene family in 22 mammalian genomes, confirming the existence of 30 KRTAP subfamilies evolving at different rates with varying degrees of diversification and homogenization. Within the two major classes of KRTAPs, the high cysteine (HS) subfamily experienced strong concerted evolution, high rates of gene conversion/recombination and high GC content. In contrast, high glycine-tyrosine …

Population Genetic Structure Of Traditional Populations In The Peruvian Central Andes And Implications For South American Population History, Graciela S. Cabana, Cecil M. Lewis, Jr., Raúl Y. Tito, R. Alan Covey, Angela M. Cáceres, C. Leslie Castillo Pampas, Augusto F. De La Cruz, Diana Durand, Genevieve Housman, Brannon I. Hulsey, Gian Carlo Iannacone, Paul W. Lopez, Rolando Martínez, Ángel Medina, Olimpio Ortega Dávila, Karla Paloma Osorio Pinto, Susan I. Polo Santillán, Percy Rojas Domínguez, Meagan Rubel, Heather F. Smith, Silvia E. Smith, Verónica Rubín De Celis, Beatriz Lizárraga, Anne C. Stone

Human Biology Open Access Pre-Prints

Molecular-based characterizations of Andean peoples are traditionally conducted in the service of elucidating continental-level evolutionary processes in South America. Consequently, “western” Andean population genetic variation is often represented in relation to “eastern” variation among Amazon and Orinoco River Basin populations. This west-east contrast in patterns of population genetic variation is typically attributed to large-scale phenomena, such as dual founder colonization events and/or differing long-term microevolutionary histories. However, alternative explanations that consider the nature and causes of population genetic diversity within the Andean region remain underexplored.

Here we examine population genetic diversity in the Peruvian Central Andes using mtDNA HVI and …

Global Population-Specific Variation In Mirna Associated With Cancer Risk And Clinical Biomarkers, Renata Rawlings-Goss, Michael Campbell, Sarah Tishkoff

Department of Biology Faculty Publications

Background: MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes.

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations and Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …