Genomics Commons^™

Mendelian Breeding Units Versus Standard Sampling Strategies: Mitochondrial Dna Variation In Southwest Sardinia, Daria Sanna, Joseph G. Lorenz

All Faculty Scholarship for the College of the Sciences

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and …

Shifting Patterns Of Natural Variation In The Nuclear Genome Of Caenorhabditis Elegans, Eleanne Solorzano, Kazufusa Okamoto, Pushpa Datla, Way Sung, R. D. Bergeron, W. Kelley Thomas

Hubbard Center for Genome Studies (HCGS)

Background: Genome wide analysis of variation within a species can reveal the evolution of fundamental biological processes such as mutation, recombination, and natural selection. We compare genome wide sequence differences between two independent isolates of the nematode Caenorhabditis elegans (CB4856 and CB4858) and the reference genome (N2). Results: The base substitution pattern when comparing N2 against CB4858 reveals a transition over transversion bias (1.32:1) that is not present in CB4856. In CB4856, there is a significant bias in the direction of base substitution. The frequency of A or T bases in N2 that are G or C bases in CB4856 …

Capturing Changes In Gene Expression Dynamics By Gene Set Differential Coordination Analysis, Tianwei Yu, Yun Bai

PCOM Scholarly Works

Analyzing gene expression data at the gene set level greatly improves feature extraction and data interpretation. Currently most efforts in gene set analysis are focused on differential expression analysis - finding gene sets whose genes show first-order relationship with the clinical outcome. However the regulation of the biological system is complex, and much of the change in gene expression dynamics do not manifest in the form of differential expression. At the gene set level, capturing the change in expression dynamics is difficult due to the complexity and heterogeneity of the gene sets. Here we report a systematic approach to detect …

Improving Gene Expression Data Interpretation By Finding Latent Factors That Co-Regulate Gene Modules With Clinical Factors, Tianwei Yu, Yun Bai

PCOM Scholarly Works

Background: In the analysis of high-throughput data with a clinical outcome, researchers mostly focus on genes/proteins that show first-order relations with the clinical outcome. While this approach yields biomarkers and biological mechanisms that are easily interpretable, it may miss information that is important to the understanding of disease mechanism and/or treatment response. Here we test the hypothesis that unobserved factors can be mobilized by the living system to coordinate the response to the clinical factors.Results: We developed a computational method named Guided Latent Factor Discovery (GLFD) to identify hidden factors that act in combination with the observed clinical factors to …

Analysis Of Biological Features Associated With Meiotic Recombination Hot And Cold Spots In Saccharomyces Cerevisiae, Loren Hansen, Nak-Kyeong Kim, Leonardo Mariño-Ramírez, David Landsman

Mathematics & Statistics Faculty Publications

Meiotic recombination is not distributed uniformly throughout the genome. There are regions of high and low recombination rates called hot and cold spots, respectively. The recombination rate parallels the frequency of DNA double-strand breaks (DSBs) that initiate meiotic recombination. The aim is to identify biological features associated with DSB frequency. We constructed vectors representing various chromatin and sequence-based features for 1179 DSB hot spots and 1028 DSB cold spots. Using a feature selection approach, we have identified five features that distinguish hot from cold spots in Saccharomyces cerevisiae with high accuracy, namely the histone marks H3K4me3, H3K14ac, H3K36me3, and H3K79me3; …

Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator

Department of Biological Sciences Publications

A total of 7194 faecal samples collected over a 1-year period from patients presenting with diarrhoea were screened for Campylobacter spp. using EntericBios, a multiplex-PCR system. Of 349 Campylobacter-positive samples, 23.8% were shown to be Campylobacter ureolyticus, using a combination of 16S rRNA gene analysis and highly specific primers targeting the HSP60 gene of this organism. This is, to the best of our knowledge, the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis and may suggest a role for this organism as an emerging enteric pathogen.

Genomic Variation And Adaptation In Africa: Implications For Human Evolutionary History And Disease, Michael Campbell

Department of Biology Faculty Publications

Africa contains the greatest levels of human genetic variation and is the source of the worldwide range expansion of all modern humans. However, relatively little is known about genomic variation in ethnically diverse African populations.

Dorsal Eye Selector Pannier (Pnr) Suppresses The Eye Fate To Define Dorsal Margin Of The Drosophila Eye, Sarah M. Oros, Meghana Tare, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Axial patterning is crucial for organogenesis. During Drosophila eye development, dorso-ventral (DV) axis determination is the first lineage restriction event. The eye primordium begins with a default ventral fate, on which the dorsal eye fate is established by expression of the GATA-1 transcription factor pannier (pnr). Earlier, it was suggested that loss of pnr function induces enlargement in the dorsal eye due to ectopic equator formation. Interestingly, we found that in addition to regulating DV patterning, pnr suppresses the eye fate by downregulating the core retinal determination genes eyes absent (eya), sine oculis (so) and dacshund (dac) to define the …

Following Tetraploidy In Maize, A Short Deletion Mechanism Removed Genes Preferentially From One Of The Two Homeologs, Margaret R. Woodhouse, James C. Schnable, Brent S. Pedersen, Eric Lyons, Damon Lisch, Shabarinath Subramaniam, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

Previous work in Arabidopsis showed that after an ancient tetraploidy event, genes were preferentially removed from one of the two homeologs, a process known as fractionation. The mechanism of fractionation is unknown. We sought to determine whether such preferential, or biased, fractionation exists in maize and, if so, whether a specific mechanism could be implicated in this process. We studied the process of fractionation using two recently sequenced grass species: sorghum and maize. The maize lineage has experienced a tetraploidy since its divergence from sorghum approximately 12 million years ago, and fragments of many knocked-out genes retain enough sequence similarity …

The Human Oral Microbiome Database: A Web-Accessible Resource For Investigating Oral Microbe Taxonomic And Genomic Information, Tsute Chen, Wen-Han Yu, Jacques Izard, Oxana V. Baranova, Abirami Lakshmanan, Floyd E. Dewhirst

Department of Food Science and Technology: Faculty Publications

The human oral microbiome is the most studied human microflora, but 53% of the species have not yet been validly named and 35% remain uncultivated. The uncultivated taxa are known primarily from 16S rRNA sequence information. Sequence information tied solely to obscure isolate or clone numbers, and usually lacking accurate phylogenetic placement, is a major impediment to working with human oral microbiome data. The goal of creating the Human Oral Microbiome Database (HOMD) is to provide the scientific community with a body site-specific comprehensive database for the more than 600 prokaryote species that are present in the human oral cavity …

A Brain-Specific Cytochrome P450 Responsible For The Majority Of Deltamethrin Resistance In The Qtc279 Strain Of Tribolium Castaneum, Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli

Entomology Faculty Publications

Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared …

A New Tumor Suppressor Gene Candidate Regulated By The Non-Coding Rna Pca3 In Human Prostate Cancer, Alessandro K. Lee

Dissertations and Theses (Open Access)

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease.

In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it …

The Rho Family Gtpase: Determining Gef Specificity Through Recombinant Expression, Farrah Steinke

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

Metagenomes From High-Temperature Chemotrophic Systems Reveal Geochemical Controls On Microbial Community Structure And Function, William P. Inskeep, Douglas B. Rusch, Zackary J. Jay, Markus J. Herrgard, Mark A. Kozubal, Toby H. Richardson, Richard E. Macur, Natsuko Hamamura, Ryan Dem. Jennings, Bruce W. Fouke, Anna-Louise Reysenbach, Frank Roberto, Mark Young, Ariel Schwartz, Eric S. Boyd, Jonathan H. Badger, Eric J. Mathur, Alice C. Ortmann, Mary Bateson, Gill Geesey

Biology Faculty Publications and Presentations

The Yellowstone caldera contains the most numerous and diverse geothermal systems on Earth, yielding an extensive array of unique high-temperature environments that host a variety of deeply-rooted and understudied Archaea, Bacteria and Eukarya. The combination of extreme temperature and chemical conditions encountered in geothermal environments often results in considerably less microbial diversity than other terrestrial habitats and offers a tremendous opportunity for studying the structure and function of indigenous microbial communities and for establishing linkages between putative metabolisms and element cycling. Metagenome sequence (14-15,000 Sanger reads per site) was obtained for five hightemperature (>65°C) chemotrophic microbial communities sampled from …

Reconstructability Analysis As A Tool For Identifying Gene-Gene Interactions In Studies Of Human Diseases, Stephen Shervais, Patricia L. Kramer, Shawn K. Westaway, Nancy J. Cox, Martin Zwick

Complex Systems Faculty Publications and Presentations

There are a number of common human diseases for which the genetic component may include an epistatic interaction of multiple genes. Detecting these interactions with standard statistical tools is difficult because there may be an interaction effect, but minimal or no main effect. Reconstructability analysis (RA) uses Shannon’s information theory to detect relationships between variables in categorical datasets. We applied RA to simulated data for five different models of gene-gene interaction, and find that even with heritability levels as low as 0.008, and with the inclusion of 50 non-associated genes in the dataset, we can identify the interacting gene pairs …

Implications Of The Plastid Genome Sequence Of Typha (Typhaceae, Poales) For Understanding Genome Evolution In Poaceae, Mary M. Guisinger, Timothy W. Chumley, Jennifer V. Kuehl, Jeffrey L. Boore, Robert K. Jansen

All Faculty Scholarship for the College of the Sciences

Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the first non-grass Poales sequenced to date, and we present comparisons of genome organization and sequence evolution within Poales. Our results confirm that grass plastid genomes exhibit acceleration in both genomic rearrangements and nucleotide substitutions. Poaceae have multiple structural rearrangements, including …

Web-Based, Participant-Driven Studies Yield Novel Genetic Associations For Common Traits, Nicholas Eriksson, J. Michael Macpherson, Joyce Y. Tung, Lawrence S. Hon, Brian Naughton, Serge Saxonov, Linda Avey, Anne Wojcicki, Itsik Pe'er, Joanna Mountain

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here …

Insights Into Genome Functional Organisation Through The Analysis Of Interaction Networks, Andre Masella

Theses and Dissertations (Comprehensive)

Using computational techniques to identify orthology and operon structure, it is possible to find functional interactions between genes, which, together, define the genetic interactome. These large networks contain information about the relationships between phenotypes in organisms as genes responsible for related abilities are often co-regulated and reasserting of these genes can be detected in the operon structure. However, these networks are too large to analyse by hand In order to practically analyse the networks, a computational tool, gisql, was developed and, using this tool, the connectivity patterns in the genetic interactome can be analysed to understand high-level organisation of …

Density Based Pruning For Identification Of Differentially Expressed Genes From Microarray Data, Jianjun Hu, J. Xu

Faculty Publications

Motivation

Identification of differentially expressed genes from microarray datasets is one of the most important analyses for microarray data mining. Popular algorithms such as statistical t-test rank genes based on a single statistics. The false positive rate of these methods can be improved by considering other features of differentially expressed genes.

Results

We proposed a pattern recognition strategy for identifying differentially expressed genes. Genes are mapped to a two dimension feature space composed of average difference of gene expression and average expression levels. A density based pruning algorithm (DB Pruning) is developed to screen out potential differentially expressed genes usually …

Building The Genomic Base-Layer Of The Oral “Omic” World, Forsyth Metagenomic Support Consortium, Jacques Izard

Department of Food Science and Technology: Faculty Publications

With the shift of molecular technologies directed toward the understanding of greater biological complexity of the oral cavity, a knowledge gap was created by the lack of genomic data from the diverse oral microorganisms. To facilitate and enable the interpretation of metagenomic, transcriptomic, and proteomic data generated or soon to be generated from oral biofilms, we are providing reference genomic information from phylogenetically diverse oral bacterial isolates. This work, initiated by the National Institute of Dental and Craniofacial Research as an isolated effort, is now part of the Human Microbiome Project. The goal of this effort is the public release …

Transcription Analysis Of The Chlorovirus Paramecium Bursaria Chlorella Virus-1, Giane M. Yanai

School of Biological Sciences: Dissertations, Theses, and Student Research

Paramecium bursaria chlorella virus (PBCV-1), a member of the family Phycodnaviridae, is a large dsDNA, plaque-forming virus that infects the unicellular green alga Chlorella NC64A. The 331 kb PBCV-1 genome is predicted to encode 365 proteins and 11 tRNAs. To follow global transcription during PBCV-1 replication, a microarray containing 50-mer probes to the PBCV-1 365 protein-encoding genes (CDS) was constructed. Competitive hybridization experiments were conducted employing cDNAs from poly A-containing RNAs obtained from cells at seven time points after virus infection. The results led to the following conclusions: i) the PBCV-1 replication cycle is temporally programmed and regulated; ii) 360 …

5q- Myelodysplastic Syndromes: Chromosome 5q Genes Direct A Tumor-Suppression Network Sensing Actin Dynamics, K. M. Eisenmann, K. J. Dykema, Stephen F. Matheson, N. F. Kent

University Faculty Publications and Creative Works

Complete loss or interstitial deletions of chromosome 5 are the most common karyotypic abnormality in myelodysplastic syndromes (MDSs). Isolated del(5q)/5q- MDS patients have a more favorable prognosis than those with additional karyotypic defects, who tend to develop myeloproliferative neoplasms (MPNs) and acute myeloid leukemia. The frequency of unbalanced chromosome 5 deletions has led to the idea that 5q harbors one or more tumor-suppressor genes that have fundamental roles in the growth control of hematopoietic stem/progenitor cells (HSCs/HPCs). Cytogenetic mapping of commonly deleted regions (CDRs) centered on 5q31 and 5q32 identified candidate tumor-suppressor genes, including the ribosomal subunit RPS14, the transcription …

Attempts To Cultivate Bacteria From Deep Subsurface Aquifers And Mountaintop Plant Communities, Eric D. Hughes, J. C. Bruckner, Duane P. Moser

Undergraduate Research Opportunities Program (UROP)

In the late 1990s, the limits of life were pushed even further when microorganisms were discovered thriving 2.5 km below the surface of the Earth in deep South African gold mines. These very simple communities were dominated by a single species of bacteria from within the phylum, Firmicutes. Desulforudis audaxviator remains unique to a sizeable portion of the South African deep subsurface. At depths below 2.5km, it comprises well over 99% of all organisms present, which presents a unique circumstance in which the environment has provided a natural pure culture. From this naturally occurring pure culture, environmental genomics was applied …

Bridging Functional Genomics And Toxicogenomics Through Dna Microarrays In A Fish Model, Shuzhao Li

Dissertations

In a case study of finding gene expression signatures for environmental stressors in Cyprinodon variegatus, this dissertation examines several important issues of applying DNA microarray technology to fish toxicogenomics. The most relevant disciplines, fish toxicogenomics and computational systems biology are reviewed in Chapter 1. Chapter 2 reviews major aspects of DNA microarray technology.

On DNA microarrays, even for probes that target the same transcript, large variations are seen in the probe signals. These variations are partly dependent and partly independent on probe sequences. Chapter 3 estimates the sequence independent variation by combining experimental and computational approaches. Chapter 4 and …

Evaluation Of Annotation Performances Between Automated And Curated Databases Of E.Coli Using The Correlation Coefficient, Reddysalilaja Marpuri

Masters Theses & Specialist Projects

This project compared the performance of the correlation coefficient to show similarities in annotations between a predictive automated bacterial annotation database and the curated EcoCyc database. EcoCyc is a conservative multidimensional annotation system that is exclusively based on experimentally validated findings by over 15,000 publications. The automated annotation system, used in the comparison was BASys. It is often used as a first pass annotation tool that tries to add as many annotations as possible by drawing upon over 30 information sources. Gene ontology served as one basis of comparison between these databases because of the limited common terms in the …

Comparison Of Gene Ontology Term Annotations Between E.Coli K12 Databases, Reddysailaja Marpuri

Student Research Conference Select Presentations

The objective of this project was to get up-to-date functional information on all genes of E.coli K12 strains based on Genome Ontology terms. Gene Ontology is described by a defined library of terms related the biological process, cellular components and molecular functions of a gene in an organism. The genome sequence of an organism gains its value when it is annotated with gene ontology terms, which bridges the gap from the sequence to the biology of an organism. Since we use annotated gene database in the prediction of the function of newly sequenced genes, it is important to have databases …

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 …

Pervasive Hitchhiking At Coding And Regulatory Sites In Humans, James J. Cai, J. Michael Macpherson, Guy Sella, Dmitri A. Petrov

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald–Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying …

A Kinship-Based Modification Of The Armitage Trend Test To Address Hidden Population Structure And Small Differential Genotyping Errors, Cyril Rakovski, Daniel O. Stram

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background/Aims We propose a modification of the well-known Armitage trend test to address the problems associated with hidden population structure and hidden relatedness in genome-wide case-control association studies.

Methods The new test adopts beneficial traits from three existing testing strategies: the principal components, mixed model, and genomic control while avoiding some of their disadvantageous characteristics, such as the tendency of the principal components method to over-correct in certain situations or the failure of the genomic control approach to reorder the adjusted tests based on their degree of alignment with the underlying hidden structure. The new procedure is based on Gauss-Markov …

Inference, Orthology, And Inundation: Addressing Current Challenges In The Field Of Metagenomics, Gregory Detlev Alexander Vey

Theses and Dissertations (Comprehensive)

The vast increase in the number of sequenced genomes has irreversibly changed the landscape of the biological sciences and has spawned the current post-genomic era of research. Genomic data have illuminated many adaptation and survival strategies between species and their habitats. Moreover, the analysis of prokaryotic genomic sequences is indispensible for understanding the mechanisms of bacterial pathogens and for subsequently developing effective diagnostics, drugs, and vaccines. Computational strategies for the annotation of genomic sequences are driven by the inference of function from reference genomes. However, the effectiveness of such methods is bounded by the fractional diversity of known genomes. Although …