Genetics and Genomics Commons^™

The Effect Of Maternal Dietary Habits During Pregnancy On Neonate Leptin Methylation Patterns And Gestational Age, Sean Fitzpatrick

Legacy Theses & Dissertations (2009 - 2024)

The health of a newborn baby is inextricably linked to the health status of its mother and in turn the mother’s diet during pregnancy. Leptin (LEP) is an adipokine hormone involved in metabolism regulation and has been linked fetal development through the hypothalamic-pituitary-adrenal axis (HPA). Prior work suggests that gestational epigenetic alterations the LEP gene may be sensitive to adverse exposures during pregnancy, which in turn could explain variation in neonate outcomes. However, no prior work has examined this possibility explicitly. The objective of this study was to investigate the association between dietary patterns of mothers during pregnancy and their …

Characterization Of Chromosomal Translocations In A Group Of Killifish Species By Using Genome-Wide High-Density Snp Mapping Approach, Naznin Sultana Remex

Masters Theses

"The role of chromosomal rearrangements in reproductive isolation and introgression between species is poorly understood. In heterozygous form, rearrangements may directly interrupt meiotic progression leading to partial sterility/subfertility (underdominance) or may suppress local meiotic segregation (recombination suppression). Such unbalanced meiotic segregation may also result in reproductive isolation and play roles as a driving force of speciation. The objective of this study was to gain insight into the pattern of chromosomal rearrangements in two closely related killifish species in the genus Fundulus (F. notatus, and F. olivaceus) by constructing genetic linkage maps using high-resolution single nucleotide polymorphism (SNP) …

Application And Refinement Of Molecular Ecology Techniques For Amphibian Conservation, Stephanie Marie Burgess

Electronic Theses and Dissertations

Wildlife conservation has become increasingly difficult due to habitat loss habitat fragmentation and land use change. Thus conservationists have embraced advances in molecular ecology such as landscape genetics and microbial bioinformatics that employ genetic techniques to further understand the relationship between individuals and their environment. In landscape genetics model inferences can be used to identify features that facilitate or resist gene flow providing a framework for anticipating the impacts of land use changes on a species’ ability to disperse. However the factors that affect the transferability of landscape genetics inferences are poorly understood and little is known about the effect …

A Novel Snp Genotyping Technique To Determine Orangutan Relatedness And Genetic Diversity At Camp Leakey In Tanjung Puting, Central Kalimantan, Ruth Ella Linsky

All Master's Theses

Genetic studies of dispersal patterns in wild populations of orangutans (Pongo spp.) have sought to confirm behavioral observations that female orangutans tend to stay near their natal range while males disperse. In order to genotype a previously unsampled wild population of endangered orangutans at Tanjung Puting National Park I developed novel application of a methyl based magnetic capture for enrichment of fecal DNA and commercial human targeted single nucleotide polymorphism (SNP) microarray technology. I confirmed results of this new genotyping technique through standard microsatellite short tandem repeat (STR) micro-capillary genotyping. I estimate genetic diversity and relatedness (r) …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Population Health Of Spotted Salamanders (Ambystoma Maculatum) In Created Vernal Pools: An Integrative Approach, Alice R. Millikin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Habitat creation is an important tool for conservation to counteract habitat loss and degradation. Vernal pools are susceptible to destruction due to limited detection, protection, and regulation. These wetlands provide fishless breeding habitat for many amphibian species including spotted salamanders (Ambystoma maculatum) in eastern North America. Determining whether created vernal pool habitat is successful is often determined by demographic data of colonizing populations. I suggest that hormone levels, population genetics, and disease prevalence can improve our understanding of population health in created habitat. The goal of this dissertation was to assess the health of spotted salamander larvae in …

Discerning Novel Splice Junctions Derived From Rna-Seq Alignment: A Deep Learning Approach, Yi Zhang, Xinan Liu, James N. Macleod, Jinze Liu

Computer Science Faculty Publications

Background: Exon splicing is a regulated cellular process in the transcription of protein-coding genes. Technological advancements and cost reductions in RNA sequencing have made quantitative and qualitative assessments of the transcriptome both possible and widely available. RNA-seq provides unprecedented resolution to identify gene structures and resolve the diversity of splicing variants. However, currently available ab initio aligners are vulnerable to spurious alignments due to random sequence matches and sample-reference genome discordance. As a consequence, a significant set of false positive exon junction predictions would be introduced, which will further confuse downstream analyses of splice variant discovery and abundance estimation.

Results: …

Power In Pairs: Assessing The Statistical Value Of Paired Samples In Tests For Differential Expression, John R. Stevens, Jennifer S. Herrick, Roger K. Wolff, Martha L. Slattery

Mathematics and Statistics Faculty Publications

Background: When genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.

Results: We demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of …

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …

A Logitudinal Feature Selection Method Identifies Relevant Genes To Distinguish Complicated Injury And Uncomplicated Injury Over Time, Suyan Tian, Chi Wang, Howard H. Chang

Biostatistics Faculty Publications

Background: Feature selection and gene set analysis are of increasing interest in the field of bioinformatics. While these two approaches have been developed for different purposes, we describe how some gene set analysis methods can be utilized to conduct feature selection.

Methods: We adopted a gene set analysis method, the significance analysis of microarray gene set reduction (SAMGSR) algorithm, to carry out feature selection for longitudinal gene expression data.

Results: Using a real-world application and simulated data, it is demonstrated that the proposed SAMGSR extension outperforms other relevant methods. In this study, we illustrate that a gene’s expression profiles over …

Breeding For Resilience To Increasing Temperatures: A Field Trial Assessing Genetic Variation In Soft Red Winter Wheat, Kathleen Russell, David Van Sanford

Plant and Soil Sciences Faculty Publications

Breeding for resilience to climate change is a daunting prospect. Crop and climate models tell us that global wheat yields are likely to decline as the climate warms, causing a significant risk to global food security. High temperatures are known to affect crop development yet breeding for tolerance to heat stress is difficult to achieve in field environments. We conducted an active warming study over two years to quantify the effects of heat stress on genetic variation of soft red winter (SRW) wheat (Triticum aestivum L.). Forty SRW cultivars and breeding lines were chosen based on marker genotypes at …

Integrating Multiple Genetic Detection Methods To Estimate Population Density Of Social And Territorial Carnivores, Sean M. Murphy, Ben C. Augustine, Jennifer R. Adams, Lisette P. Waits, John J. Cox

Forestry and Natural Resources Faculty Publications

Spatial capture–recapture models can produce unbiased estimates of population density, but sparse detection data often plague studies of social and territorial carnivores. Integrating multiple types of detection data can improve estimation of the spatial scale parameter (σ), activity center locations, and density. Noninvasive genetic sampling is effective for detecting carnivores, but social structure and territoriality could cause differential detectability among population cohorts for different detection methods. Using three observation models, we evaluated the integration of genetic detection data from noninvasive hair and scat sampling of the social and territorial coyote (Canis latrans). Although precision of estimated density was …

Seqothello: Querying Rna-Seq Experiments At Scale, Ye Yu, Jinpeng Liu, Xinan Liu, Yi Zhang, Eamonn Magner, Erik Lehnert, Chen Qian, Jinze Liu

Computer Science Faculty Publications

We present SeqOthello, an ultra-fast and memory-efficient indexing structure to support arbitrary sequence query against large collections of RNA-seq experiments. It takes SeqOthello only 5 min and 19.1 GB memory to conduct a global survey of 11,658 fusion events against 10,113 TCGA Pan-Cancer RNA-seq datasets. The query recovers 92.7% of tier-1 fusions curated by TCGA Fusion Gene Database and reveals 270 novel occurrences, all of which are present as tumor-specific. By providing a reference-free, alignment-free, and parameter-free sequence search system, SeqOthello will enable large-scale integrative studies using sequence-level data, an undertaking not previously practicable for many individual labs.

Iac Gene Expression In The Indole-3-Acetic Acid-Degrading Soil Bacterium Enterobacter Soli Lf7, Isaac V. Greenhut, Beryl L. Slezak, Johan H. J. Leveau

Plant and Soil Sciences Faculty Publications

We show for soil bacterium Enterobacter soli LF7 that the possession of an indole-3-acetic acid catabolic (iac) gene cluster is causatively linked to the ability to utilize the plant hormone indole-3-acetic acid (IAA) as a carbon and energy source. Genome-wide transcriptional profiling by mRNA sequencing revealed that these iac genes, chromosomally arranged as iacHABICDEFG and coding for the transformation of IAA to catechol, were the most highly induced (>29-fold) among the relatively few (iac cluster were genes for a major facilitator superfamily protein (mfs) and enzymes of the β-ketoadipate pathway (pcaIJD-catBCA), which channels …

Longitudinal Data Methods For Evaluating Genome-By-Epigenome Interactions In Families, Justin C. Strickland, I-Chen Chen, Chanung Wang, David W. Fardo

Psychology Faculty Publications

Background: Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data.

Results: Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score.

Conclusions: Comparison of all modeling approaches indicated …

Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy

Biostatistics Faculty Publications

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …

Association Analyses Of Repeated Measures On Triglyceride And High-Density Lipoprotein Levels: Insights From Gaw20, Saurabh Ghosh, David W. Fardo

Biostatistics Faculty Publications

Background: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided “real” data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set.

Results: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of …

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 …

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 …

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

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 …

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 …

Scale-Invariant Geometric Data Analysis (Sigda), Marina Girgis, Max Robinson

STAR Program Research Presentations

The purpose of this research is to introduce a new data analysis method called Scale Invariant Geometric Data Analysis (SIGDA). SIGDA has been shown to be more informative than more common data analysis methods, such as Principal Component Analysis (PCA). SIGDA is used to visualize complex data sets in a way that accurately preserves data patterns and behavior. SIGDA is designed to preserve relative ratios in a numerical matrix, and the number of entries has to be more than the total number of rows and columns. Our research involved providing a simple explanation of SIGDA's mathematical process—simple enough for the …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Genome-Wide Atlas Of Alternative Polyadenylation In The Forage Legume Red Clover, Manohar Chakrabarti, Randy D. Dinkins, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Studies on prevalence and significance of alternative polyadenylation (APA) in plants have been so far limited mostly to the model plants. Here, a genome-wide analysis of APA was carried out in different tissue types in the non-model forage legume red clover (Trifolium pratense L). A profile of poly(A) sites in different tissue types was generated using so-called ‘poly(A)-tag sequencing’ (PATseq) approach. Our analysis revealed tissue-wise dynamics of usage of poly(A) sites located at different genomic locations. We also identified poly(A) sites and underlying genes displaying APA in different tissues. Functional categories enriched in groups of genes manifesting APA between …

Identifying Kif Subtype That Mediates Axonal Targeting Of Kv7 Channels, Allison Houghton, Jennifer Walters, Mary Hong, Dhruv Joshi, Hee Jung Chung

PRECS 2018

Early-onset Benign Familial Neonatal Epilepsy (BFNE) and Epileptic Encephalopathy (EE), are associated with mutations in neuronal KCNQ/Kv7 channel subunits Kv7.2 and Kv7.3. Kv7 channels are voltage-dependent potassium channels. Enriched at the axonal plasma membrane, they pump potassium ions out of the neurons and inhibit repetitive or burst firing of action potentials. A single neuronal Kv7 channel is a heterotetramer composed of two Kv7.2 and two Kv7.3 subunits. BFNE and EE mutations in Kv7.2 and Kv7.3 lead to decreased surface expression along the axon, which means less potassium ions are moved across the axonal membrane where action potentials are generated and …

Production Of Bioactive Isothiocyanates By Bacterial Myrosinase, Juan Isaiz, Xiaoji Liu, Michael J. Miller

PRECS student projects

Isothiocyanates (ITCs) are bioactive products found in several plants belonging to the Brassicaceae family, and are produced as defense upon disruption of the tissue by herbivores or pathogens, but in humans they have shown anti-cancer and anti-inflammatory properties.

Although we know gut microbes can hydrolyze GSL into ITC, the mechanism is not known. With improved detection methods, the aim of this experiment is to explore whether the gut microbial myrosinase β-glucosidase found within the genome of E. coli Nissle 1917 can hydrolyze glucosinolates (GSLs) into detectable ITCs.

Sperm-Mediated Effects Of Predation Risk On Reproduction In Male Threespined Sticklebacks, Shayne Kempfer, Erika Carlson, Jennifer Hellmann, Jason Keagy, Alison Bell

PRECS student projects

Threespined sticklebacks, Gasterosteus aculeatus, exhibit male-only parental care, but will decrease paternal care if exposed to predators while given care or if their mate has had prior experiences with predators. The offspring will experience lasting effects based on the experience of their parents (behavior-mediated transgenerational plasticity). While other studies have concluded that male exposure to predators prior to fertilization (sperm-mediated transgenerational plasticity) impacts offspring, whether sperm-mediated effects exist in sticklebacks, and for how many generations the effects persist is unknown. Courtship trials with both predator exposed and predator unexposed females with six male treatment groups shows significant impact of maternal …

How Does Climate Change Affect Endophytic Fungi?, Amber Toussaint, Natalie Christian, Katy Heath

PRECS student projects

Plant-associated microorganisms can have major effects on plant health, but climate change can affect plant microbiomes. While it is unknown how climate change will affect aboveground plant-associated microorganisms, such as foliar endophytic fungi, we hypothesize that increased CO₂ concentrations will increase species richness and diversity in endophytic fungal communities, because increased plant photosynthesis under elevated CO₂ will increase the resources available to the fungi.