Genetics Commons^™

Exome Array Analysis Of 9721 Ischemic Stroke Cases From The Sign Consortium, Huichun Xu, Kevin Nguyen, Brady J Gaynor, Hua Ling, Wei Zhao, Patrick F Mcardle, Timothy D O'Connor, O Colin Stine, Kathleen A Ryan, Megan Lynch, Jennifer A Smith, Jessica D Faul, Yao Hu, Jeffrey W Haessler, Myriam Fornage, Charles Kooperberg, On Behalf Of The Trans-Omics For Precision Medicine Topmed Stroke Working Group, James A Perry, Charles C Hong, John W Cole, Elizabeth Pugh, Kimberly Doheny, Sharon L R Kardia, David R Weir, Steven J Kittner, Braxton D Mitchell, Sign Consortium

Faculty, Staff and Student Publications

Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., p < 4.7 × 10-7), including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare …

Dissecting Interactions Across Gene Regulatory Layers In C. Elegans, Morgan Taylor

Biological Sciences Theses and Dissertations

The nematode Caenorhabditis elegans is a powerful tool for studying nervous system genetics. Though relatively simple compared to mammals, C. elegans boasts a remarkably well-conserved neuronal genome and proteome, and its utility in the characterization of neuronal genes has been well-established. However, gene expression is often controlled by complex interactions between multiple genes, and teasing apart the functions of individual genes within such networks remains a challenge. Dissecting these interaction networks is crucial in determining the multifaceted functions of important, conserved regulatory genes. Here we explore interactions between gene regulatory layers in the C. elegans nervous system, employing a synthetic …

Deciphering The Mechanism And Function Of Hsp100 Unfoldases From Protein Structure, Grace Lee, Rebecca S Kim, Sang Bum Lee, Sukyeong Lee, Francis T F Tsai

Faculty, Staff and Students Publications

Hsp100 chaperones, also known as Clp proteins, constitute a family of ring-forming ATPases that differ in 3D structure and cellular function from other stress-inducible molecular chaperones. While the vast majority of ATP-dependent molecular chaperones promote the folding of either the nascent chain or a newly imported polypeptide to reach its native conformation, Hsp100 chaperones harness metabolic energy to perform the reverse and facilitate the unfolding of a misfolded polypeptide or protein aggregate. It is now known that inside cells and organelles, different Hsp100 members are involved in rescuing stress-damaged proteins from a previously aggregated state or in recycling polypeptides marked …

Development Of Functional Markers For Resistance To Smut And Identification Of Genes Differentially Expressed In Response To Brown Rust In Sugarcane, Jose David Cortes

LSU Doctoral Dissertations

Smut, caused by Sporisorium scitamineum and brown rust, caused by Puccinia melanocephala, are two of the most important diseases that affect sugarcane production in Louisiana and worldwide. Smut continues to cause losses in the breeding program in Louisiana. Therefore, a QTL analysis was conducted to identify molecular markers associated with resistance in F₁ progeny (162) of a biparental cross between susceptible cultivar L 99-233 and resistant HoCP 96-540. Using 1,574 single-dose SNP markers, a total of 253 linkage groups (LG) were obtained with a genome coverage of 24,580.15 cM. Six QTLs were localized on five LGs. The highest …

The Influence Of Taste Sensitivity To 6-N-Propylthiouracil (Prop) On Anthropometric Measurements, Body Composition, And Eating Behaviors Among Female College Students, Abeer Mohammedsharief Alardawi

Theses and Dissertations

Taste is one of the crucial factors that contributes to shaping eating behaviors and is also one of the leading reasons that affects our preferences to like or dislike some foods that mainly have a bitter taste. Variation in bitter phenotype (tasters and non-tasters) could influence diet quality and in turn body weight, which overall influenced health outcomes. The objective of this study was to identify whether bitter taste phenotype status influences anthropometric measurements, body fat percentage, and eating behaviors (liking and intake) in female college students. In this cross-sectional study (n = 86), female college students aged 18 to …

Lpa Disruption With Aav-Crispr Potently Lowers Plasma Apo(A) In Transgenic Mouse Model: A Proof-Of-Concept Study, Alexandria M Doerfler, So Hyun Park, Julia M Assini, Amer Youssef, Lavanya Saxena, Adam B Yaseen, Marco De Giorgi, Marcel Chuecos, Ayrea E Hurley, Ang Li, Santica M Marcovina, Gang Bao, Michael B Boffa, Marlys L Koschinsky, William R Lagor

Faculty, Staff and Students Publications

Lipoprotein(a) (Lp(a)) represents a unique subclass of circulating lipoprotein particles and consists of an apolipoprotein(a) (apo(a)) molecule covalently bound to apolipoprotein B-100. The metabolism of Lp(a) particles is distinct from that of low-density lipoprotein (LDL) cholesterol, and currently approved lipid-lowering drugs do not provide substantial reductions in Lp(a), a causal risk factor for cardiovascular disease. Somatic genome editing has the potential to be a one-time therapy for individuals with extremely high Lp(a). We generated an LPA transgenic mouse model expressing apo(a) of physiologically relevant size. Adeno-associated virus (AAV) vector delivery of CRISPR-Cas9 was used to disrupt the LPA transgene in …

Cpg Site-Based Signature Predicts Survival Of Colorectal Cancer, Jiande Wu, Lu Zhang, Aditi Kuchi, David Otohinoyi, Chindo Hicks

School of Medicine Faculty Publications

Background: A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC. Methods: We analyzed DNA methylation patterns between tumor and control samples …

Rad51-Mediated Interhomolog Recombination During Budding Yeast Meiosis Is Promoted By The Meiotic Recombination Checkpoint And The Conserved Pif1 Helicase, Andrew Ziesel, Qixuan Weng, Jasvinder S. Ahuja, Abhishek Bhattacharya, Raunak Dutta, Evan Cheng, G. Valentin Borner Ph.D., Michael Lichten, Nancy M. Hollingsworth

Biological, Geological, and Environmental Faculty Publications

During meiosis, recombination between homologous chromosomes (homologs) generates crossovers that promote proper segregation at the first meiotic division. Recombination is initiated by Spo11-catalyzed DNA double strand breaks (DSBs). 5' end resection of the DSBs creates 3' single strand tails that two recombinases, Rad51 and Dmc1, bind to form presynaptic filaments that search for homology, mediate strand invasion and generate displacement loops (D-loops). D-loop processing then forms crossover and noncrossover recombinants. Meiotic recombination occurs in two temporally distinct phases. During Phase 1, Rad51 is inhibited and Dmc1 mediates the interhomolog recombination that promotes homolog synapsis. In Phase 2, Rad51 becomes active …

Interneuronal Network Model Of Theta-Nested Fast Oscillations Predicts Differential Effects Of Heterogeneity, Gap Junctions And Short Term Depression For Hyperpolarizing Versus Shunting Inhibition, Guillem Via, Roman Baravalle, Fernando R. Fernandez, John A. White, Carmen C. Canavier

School of Medicine Faculty Publications

Theta and gamma oscillations in the hippocampus have been hypothesized to play a role in the encoding and retrieval of memories. Recently, it was shown that an intrinsic fast gamma mechanism in medial entorhinal cortex can be recruited by optogenetic stimulation at theta frequencies, which can persist with fast excitatory synaptic transmission blocked, suggesting a contribution of interneuronal network gamma (ING). We calibrated the passive and active properties of a 100-neuron model network to capture the range of passive properties and frequency/current relationships of experimentally recorded PV+ neurons in the medial entorhinal cortex (mEC). The strength and probabilities of chemical …

Determination Of Some Seed Characteristics Of False Flax (Camelina Sativa L. Crantz) Genotypes Grown Under Semi-Temperate Conditions, İlhan Subaşı, Yusuf Arslan, Tamer Eryigit, Vahdettin Çiftçi, Mahmut Çamlıca

The Philippine Agricultural Scientist

Camelina is an alternative low-input oil plant grown in marginal areas in Turkey. This study aimed to determine some quality characteristics of 39 camellia genotypes in ecological conditions in Bolu, Turkey. The field experiments were carried out in an augmented design with randomized blocks. In this work, some important properties such as thousand seed weight, oil content, fatty acid composition, and protein ratio were investigated. Results showed that mean data for thousand seed weight, oil ratio, and protein ratio were 0.63 – 1.5 g, 26.69 – 39.17%, and 21.81 – 29.81%, respectively. Considering the oil content of the genotypes used …

The Effect Of Spirulina Platensis Algae Inclusion In Feed Of Commercial Broilers Subjected To Cyclic Heat Stress, Kirsten Shafer

Graduate Theses and Dissertations

The effect of Spirulina platensis inclusion in feed of commercial broilers was evaluated over one experiment. The study aimed to investigate the effects of Spirulina platensis freshwater algae inclusion on live performance and processing characteristics of commercial broilers subjected to daily cyclic heat stress. Day old Ross 708 male broilers were placed into 8 environmentally controlled chambers. At d 21, four chambers remained on a control diet containing no algae (CON) while 4 chambers received a diet that included algae at an inclusion rate of 2.5% (ALG). An 8 hour daily cyclic heat stress (24°C to 36°C) was applied to …

Deciphering The Genetic Architecture Of Key Female Floral Traits For Hybrid Wheat Seed Production, Juan David Jimenez

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Wheat (Triticum aestivum L.) is a staple cereal that provides 20% of the calories and proteins in human intake (Ray et al., 2013). Global population is projected to increase to 9.7 billion by 2050. Food production must increase by 70% to feed this future population. Wheat production is in crisis due to political and environmental challenges and is projected to decline by 0.8% in 2022 (FAO, 2022). To ensure food security yield genetic gain must increase by around 1.4% annually. Taking advantage of heterosis, hybrid wheat has the potential to boost grain yield. However, hybrid wheat seed production systems …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …

Biology And Ecology Of Aedes (Stegomyia) Aegypti In The Northern Chihuahuan Desert, Adam Joseph Vera

Open Access Theses & Dissertations

Aedes aegypti is a medically important mosquito species that transmits multiple arboviruses, including dengue, chikungunya, Zika, and yellow fever. This mosquito species has expanded its geographical range into expanded into the Northern Chihuahuan Desert to further increase the risk of infection by these viruses in naïve human populations. Although Ae. aegypti is abundant along the U.S.â??Mexico border, the biology and ecology of this mosquito species in this temperate/arid climate region is not understood. The objective of this study was to understand the environmental factors that influence the invasive species of Ae. aegypti abundance, breeding habitat selection, host feeding behavior, and …

Landscape Genomics Of The Tussock Cottongrass (Eriophorum Vaginatum) And The Dwarf Birch (Betula Nana) In North Central Alaska, Elizabeth Stunz

Open Access Theses & Dissertations

Global climate change has resulted in geographic range shifts of flora and fauna at a global scale. Extreme environments, like the Arctic, are seeing some of the most pronounced changes. This region covers 14% of the Earthâ??s land area, and while many arctic species are widespread, understanding ecotypic variation at the genomic level will be important for elucidating how range shifts will affect ecological processes. Increase in shrub cover is a major effect of ongoing climate change in arctic tundra ecosystems. The relative increases in abundance and cover of shrub species such as birch, willow, and alder (Betula, Salix, and …

Potential Fitness Trade-Offs Of Elevated Esterase Activity Associated With Insecticide Resistance In The Mosquito Culex Quinquefasciatus, Timothy Schulte

Electronic Theses, Projects, and Dissertations

One of the current major issues in the control of vector-borne disease is resistance to insecticides. Resistance to one or more insecticides has appeared in over 580 different arthropod species. Widespread resistance has led to the field of Insecticide Resistance Management (IRM). The goal of IRM is to develop insecticide-use strategies that prevent or slow down the evolution of resistance. Computer models have shown that more effective IRM strategies rely on the assumption that resistance carries a fitness cost in the absence of insecticide use.

In the mosquito Culex quinquefasciatus resistance to certain organophosphate insecticides is caused by an increased …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Retrospective Varying Coefficient Association Analysis Of Longitudinal Binary Traits, Gang Xu

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many genetic studies contain rich information on longitudinal phenotypes that require powerful analytical tools for optimal analysis. Genetic analysis of longitudinal data that incorporates temporal variation is important for understanding the genetic architecture and biological variation of complex diseases. Most of the existing methods assume that the contribution of genetic variants is constant over time and fails to capture the dynamic pattern of disease progression. However, the relative influence of genetic variants on complex traits fluctuates over time.We developed several tests to fill the gap of analyzing time-varying genetic effects in longitudinal GWAS for binary traits. First, we propose a …

Defining The Role Of Core Histones In Cellular Quiescence, Eric M. Small

Biomedical Sciences ETDs

Quiescence is a distinct cell cycle phase, termed G0, in which growth, transcriptional and translational activity, and replication are halted. Importantly, quiescent cells are viable and can return to the cell cycle. Quiescence is a feature of all organisms and a key hallmark of stem cells; however, the regulation of quiescence is still poorly understood.

Prior studies have implicated chromatin in the regulation of quiescence. In aim 1 I conducted a comprehensive screen of H3 and H4 histone mutants to identify chromatin features that may affect quiescence. I identified several histone residues implicated in transcriptional regulation that altered quiescence and …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

The Conquest Of Milk: The Rise Of Lactase Persistence And The Fall Of Scandinavian Hunter-Gatherers, Nicholas Mays

James Madison Undergraduate Research Journal (JMURJ)

Over half of the global human population suffers from lactase nonpersistence, a condition marked by losing the ability to digest lactose after infancy. However, a minority of the global population, primarily located in Central and Northern Europe, has a genetic mutation that results in lactase persistence, which is the continued ability to process lactose after infancy. This interdisciplinary analysis blends archaeology, cultural anthropology, evolutionary biology, and archaeogenetics to explore the origin and rise of lactase persistence in Europe and its contribution to the end of hunter-gatherer societies in Scandinavia. Furthermore, the paper uses gene-culture coevolutionary theory to argue that lactase …

A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang

Biology Faculty Publications

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from …

Unraveling The Complex Interactions Between Members Of The Schistosoma Haematobium Group And Bulinus Snails In And Around Lake Victoria In West Kenya, Caitlin Raiselle Babbitt

Biology ETDs

Schistosoma haematobium, the agent of urogenital schistosomiasis, and related schistosomes are transmitted by members of the genus Bulinus. Each of the 38 Bulinus species vary in their ability to vector schistosome species and non-schistosome trematodes resulting in a patchwork of snail-parasite compatibilities. Accurately identifying snail intermediate hosts and the disease-causing parasites they transmit is critical for snail control strategies and the management of human schistosomiasis. Towards these ends, this thesis identifies bulinid species and the parasites they transmit and implicates certain species in the transmission of S. haematobium. The thesis also includes a systematic review of methods …

Cell Size Control Mechanisms In The Multiple Fission Cell Cycle Of Chlamydomonas, Dianyi Liu

Dissertations

Size homeostasis is achieved by a balance between cell growth and cell division, but the underlying mechanisms are yet fully understood. Green alga Chlamydomonas reinhardtii (Chlamydomonas) is a unique model for size control. Instead of the canonical binary fission cell cycle, Chlamydomonas uses a multiple fission cell cycle where a prolonged G1 phase is followed by rapid alternative n rounds of S/M (DNA synthesis and mitosis) cycles to produce 2ⁿ daughter cells. Two size checkpoints show size-dependence: the Commitment checkpoint governs a minimum size for a cell to divide at least once, and the S/M checkpoint governs the division …

Identification Of Quantitative Trait Loci (Qtls) For Resistance To Bacterial Leaf Streak: Xanthomonas Translucens Using Qtl And Association Mapping In Three Populations Of Soft Red Winter Wheat, Benjamin Tyler Meritt

LSU Doctoral Dissertations

Bacterial leaf streak (BLS) and black chaff, caused by Xanthomonas translucens pv. undulosa (Xtu), can be a very destructive disease of wheat, especially in the warmer, wetter areas of the Southeastern U.S. Yield losses of up to 40 percent have been recorded in some cases in southern wheat growing regions. With no effective agronomic or chemical method of disease control, identification of genetic resistance is seen as a promising solution. Three soft red winter wheat populations (GAWN, ARK-SNP, and AGS 2060- AGS 2035 DH) representative of soft red winter wheat germplasm in the southeastern U.S. developed by …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Lord Of The Z-Rings: Uncovering The Role Of Mraz And Ftsl In Bacillus Subtilis Cell Division, Maria Louise White

USF Tampa Graduate Theses and Dissertations

Cell division is a complex and highly orchestrated process that requires careful coordination. The process of cell division in prokaryotes primarily occurs via binary fission, where one mother cell becomes two genetically identically and equally sized daughter cells. In most bacteria a key protein, FtsZ, forms a FtsZ ring (Z-ring) to mark the division site and recruit proteins involved in cytokinesis. Whilst much has been learned about the contents and assembly of the divisome in model organisms such as Escherichia coli and Bacillus subtilis factors governing the regulation of divisome are much more poorly understood. …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

The Effect Of Infection Risk On Female Blood Transcriptomics, Brenna M. G. Gormally, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Defenses against pathogens can take on many forms. For instance, behavioral avoidance of diseased conspecifics is widely documented. Interactions with these infectious conspecifics can also, however, lead to physiological changes in uninfected animals, an effect that is much less well understood. These changes in behavior and physiology are particularly important to study in a reproductive context, where they can impact reproductive decisions and offspring quality. Here, we studied how an acute (3 h) exposure to an immune-challenged male affected female blood transcriptomics and behavior. We predicted that females paired with immune-challenged males would reduce eating and drinking behaviors (as avoidance …