Genomics Commons^™

Uncovering The Hidden Diversity Of Antibody Heavy Chains And Their Implications For Autoantibody Mediated Disease., Easton Earl Ford

Electronic Theses and Dissertations

Understanding the diversity of antibody (IG) molecules at the DNA and RNA level is imperative for understanding immunological processes and disease. Much of the work to uncover IG diversity has been focused on diversity in the variable region of the IG molecule which is crucial for antigen binding. However, the diversity of the constant region responsible for the functions of IG has largely been ignored in the field of immunogenetics. The work presented in this thesis challenges the dogma that the constant region is invariant in terms of genetic diversity. In this thesis we present the development of a long-read …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Developing A Comprehensive Genome-Scale Metabolic Model For The Arabidopsis Thaliana Root System, Lohani Esterhuizen

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Arabidopsis thaliana (Arabidopsis) is the most well-established model plant to date. Being the first plant to have its genome mapped, studies on Arabidopsis have provided insurmountable insights into the physiological and biochemical nature of plants. Methods that allow us to computationally study the metabolism of organisms include the use of genome-scale metabolic models (GEMs). Despite its popularity, no GEM currently maps the metabolic activity in the root system of Arabidopsis, which is the first organ to face and respond to stress conditions in the soil. This work aims to develop and implement a comprehensive GEM of the Arabidopsis root system …

Cherokia Georgiana Mitogenome Sequencing And Analysis, William Wittstock

Biology Theses

Despite the vast diversity of millipedes, complete genomic and mitogenomic data available in public databases is limited, hindering comprehensive studies on their classification, evolution, and genetics. Among the underrepresented taxa are the Xystodesmidae, a family comprising approximately 500 species with minimal mitogenomic data, and no complete genomes sequenced. Our research involves sequencing the mitochondrial genome of Cherokia georgiana, a representative of this diverse family with interesting traits that are not clearly defined at a genetic level. This research also serves as a pilot study to develop DNA extraction methods and protocols for whole genome sequencing. Multiple DNA extraction kits …

Crispr-Cas9 And Cas12a Target Site Richness Reflects Genomic Diversity In Natural Populations Of Anopheles Gambiae And Aedes Aegypti Mosquitoes, Travis C Collier, Yoosook Lee, Derrick K Mathias, Víctor López Del Amo

Faculty, Staff and Student Publications

Due to limitations in conventional disease vector control strategies including the rise of insecticide resistance in natural populations of mosquitoes, genetic control strategies using CRISPR gene drive systems have been under serious consideration. The identification of CRISPR target sites in mosquito populations is a key aspect for developing efficient genetic vector control strategies. While genome-wide Cas9 target sites have been explored in mosquitoes, a precise evaluation of target sites focused on coding sequence (CDS) is lacking. Additionally, target site polymorphisms have not been characterized for other nucleases such as Cas12a, which require a different DNA recognition site (PAM) and would …

Conservation Genomic Investigation Of A Threatened Trout Species Endemic To The Gila River, David Thomas Camak

Biology ETDs

Climate change is a looming threat to the persistence of species, especially aquatic, imperiled species. Species native to desert streams are at a particular disadvantage, as many species already face drought, floods, wildfires, and threats from nonnative species, all of which are thought to be exacerbated by climate change. Species such as the threatened Gila Trout (Oncorhynchus gilae) already have small ranges and persist in fragmented and isolated habitats that limits gene flow between populations. Therefore, it is important to understand the current genomic status of such populations to be able to predict the future effects of climate …

Leveraging The Genomic Tools To Explore The Molecular Basis Of Salinity Tolerance In Rice And Soybean, Rajat Pruthi

LSU Doctoral Dissertations

Salinity stress significantly challenges agricultural productivity, particularly affecting major crops like rice and soybean. This research investigates the genetic basis of salt tolerance in both crops through high-resolution genetic mapping, genome-wide association studies (GWAS), and RNA-Seq analysis. In rice, we examined quantitative trait loci (QTLs) associated with salt tolerance at the seedling and flowering stages using a population of advanced backcrossed introgression lines (ILs). A genetic map, constructed with 14,230 polymorphic SNP markers, identified distinct QTLs and candidate genes for salt tolerance at both stages, suggesting differential genetic controls. Notable genes such as OsHAK13 and OsCYP21-4 were upregulated under salt …

Ocular Gene Transfer In The Spotlight: Implications Of Newspaper Content For Clinical Communications, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of …

Evaluating Past Progress And Assessing Prediction Breeding Strategies For Sustained Genetic Gains In The Louisiana Sugarcane Variety Development Program, Brayden A. Blanchard

LSU Doctoral Dissertations

The aim of this dissertation is to outline important considerations for the Louisiana Sugarcane Variety Development Program (LSVDP) as it pertains to historical progress, impact, goal setting, and new strategies for continued genetic gains. Industry progress was evaluated with robust regression models to quantify rates of productivity gains. Over the last 50 years, statistically significant productivity gains were identified in sucrose content (45%), cane yield (32.2%), and sugar yield (93%) while pairwise comparisons of decades showed that progress was incremental rather than rapid and sustained once achieved. The decade from 1990-1999 was identified as the only decade with a significant …

Discovery Of Runs-Of-Homozygosity Diplotype Clusters And Their Associations With Diseases In Uk Biobank, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

Runs-of-homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE (runs-of-homozygous diplotype cluster enumerator), to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number …

Maldi Imaging Mass Spectrometry Visualizes The Distribution Of Antidepressant Duloxetine And Its Major Metabolites In Mouse Brain, Liver, Kidney, And Spleen Tissues, Saleh M Khalil, Xuan Qin, John M Hakenjos, Jian Wang, Zhaoyong Hu, Xinli Liu, Jin Wang, Mirjana Maletic-Savatic, Kevin R Mackenzie, Martin M Matzuk, Feng Li

Faculty, Staff and Student Publications

Imaging mass spectrometry (IMS) is a powerful tool for mapping the spatial distribution of unlabeled drugs and metabolites that may find application in assessing drug delivery, explaining drug efficacy, and identifying potential toxicity. This study focuses on determining the spatial distribution of the antidepressant duloxetine, which is widely prescribed despite common adverse effects (liver injury, constant headaches) whose mechanisms are not fully understood. We used high-resolution IMS with matrix-assisted laser desorption/ionization to examine the distribution of duloxetine and its major metabolites in four mouse organs where it may contribute to efficacy or toxicity: brain, liver, kidney, and spleen. In none …

Isolation Of Gametophytic Selection And Selective Embryo Abortion In Mimulus Guttatus, Desmond C. Willson

University Honors Theses

A lack of genomic studies examining gametophytic selection (GS) and selective embryo abortion (SEA)--which occur during the reproduction of angiosperms--leaves questions regarding the adaptive and evolutionary effects of these processes. Analyzing deviations from Mendelian segregation offers an avenue for identifying loci targeted by GS and SEA, and their contributions to purging of genetic load. However, other selective processes such as meiotic drive and cytonuclear interactions, as well as pollen and ovule abortion, can cause distortion. To distinguish the effects of GS and SEA from other causes of distortion, we will perform reciprocal crosses between highly homozygous and highly heterozygous individuals …

Effects Of Protein-Enriched Nutritional Support On Skeletal Muscle Mass And Rehabilitative Outcomes In Brain Tumor Patients: A Randomized Controlled Trial, Kye Hee Cho, Eun Young Han, Min Kyu Jung, Chang Moo Kang, Ji Cheol Shin, Sang Hee Im

Faculty, Staff and Student Publications

Patients with brain tumors require extensive and prolonged rehabilitation efforts as they suffer from lesion-induced motor weakness as well as treatment-related side effects, often leading to a significant decline in function. Protein supplements have shown positive effects on promoting muscle strength and physical performance in various tumor etiologies. However, reports on their effects specifically in brain tumor patients remain scarce. This study aims to investigate the feasibility and efficacy of protein supplements in enhancing rehabilitative outcomes via muscle strengthening and functional gain in brain tumor patients with neurological demise. Sixty brain tumor patients were randomly assigned to either a protein …

Improving Access To Exome Sequencing In A Medically Underserved Population Through The Texome Project, Blake Vuocolo, Ryan J German, Seema R Lalani, Chaya N Murali, Carlos A Bacino, Stephanie Baskin, Rebecca Littlejohn, John D Odom, Scott Mclean, Carrie Schmid, Morgan Nutter, Melissa Stuebben, Emily Magness, Olivia Juarez, Dina El Achi, Bailey Mitchell, Kevin E Glinton, Laurie Robak, Sandesh C S Nagamani, Lisa Saba, Adasia Ritenour, Lilei Zhang, Haley Streff, Katie Chan, K Jordan Kemere, Kent Carter, Texome Project, Nichole Owen, Liesbeth Vossaert, Pengfei Liu, Hugo Bellen, Michael F Wangler

Faculty, Staff and Students Publications

PURPOSE: Genomic medicine can end diagnostic odysseys for patients with complex phenotypes; however, limitations in insurance coverage and other systemic barriers preclude individuals from accessing comprehensive genetics evaluation and testing.

METHODS: The Texome Project is a 4-year study that reduces barriers to genomic testing for individuals from underserved and underrepresented populations. Participants with undiagnosed, rare diseases who have financial barriers to obtaining exome sequencing (ES) clinically are enrolled in the Texome Project.

RESULTS: We highlight the Texome Project process and describe the outcomes of the first 60 ES results for study participants. Participants received a genetic evaluation, ES, and return …

Evolution And Adaptation To Temperature In Thermotogota, Anne Amelia Farrell

Dartmouth College Ph.D Dissertations

Life thrives across incredibly diverse environmental conditions, yet most organisms are restricted to growing within a narrow range around their optimum growth temperature (OGT). The evolutionary events leading to changes in OGT are poorly understood, and it is uncertain if specific genes are required to thrive at a particular temperature. The bacterial phylum Thermotogota is an excellent model for the evolution of OGT. It comprises mesophilic, thermophilic, and hyperthermophilic members that collectively grow between 20°C and 90°C.

In this work, I analyze the history of OGT in the Thermotogota phylum and show how horizontal gene transfer contributes to the evolution …

An Unexpected Path For Malat1 In Neurons: Trafficking Out Of The Nucleus For Translation, Bradley W Wright, Jeremy E Wilusz

Faculty, Staff and Students Publications

The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of Genes & Development, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured mouse neurons are surprisingly exported from the nucleus. These transcripts are packaged with Staufen proteins in RNA granules and traffic down the lengths of neurites. They then can be released in a stimulus-dependent manner to be locally translated into a microprotein that alters neuronal gene …

Big Life-Science: Study Of Omics From Microscopic To Mesoscopic Scales, Jiarui Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The human genome project at the turn of the century opened a new era of life science research and formed various omics characterized by holistic high-throughput research. The initial omics research was mainly carried out at the molecular level, such as genomics, transcriptomics, proteomics, etc., showing a new paradigm of data-driven research. With the development of research technologies, the omics research has risen to the mesoscopic level, the representative is the “Human Cell Atlas” project launched in 2017. At present, researchers have been able to carry out omics research at the level of tissues, organs, and even individuals, and resulted …

Synthetic Biology Enablement: From Academic Development To Industrial Transformation, Yan Xiong, Xueqing Ma, Daming Chen, Xiao Liu, Guoping Zhao

Bulletin of Chinese Academy of Sciences (Chinese Version)

Synthetic biology revolutionizes the comprehension of life systems from an engineering perspective, employing a “bottomup” approach in life science research. It adopts an iterative research paradigm of “design-build-test-learn” in life science research and creates engineered new life systems grounded in genomics and systems biology. This provides a new pathway of “from creation to understanding” for life sciences, departing from the traditional reductionist research strategy of “study the whole to understand the parts” and opening up a new culture of “building to understand” the essence of life. Additionally, synthetic biology elevates existing biotechnologies previously based on “simulating natural processes” and “genetic …

Promoting Ecosystem Based Marine Management Through A Marine Ecological Classification And Zoning System, Wenhai Lu, Xiao Li, Meng Cui

Bulletin of Chinese Academy of Sciences (Chinese Version)

Ecosystem based ocean management is an important means of building marine ecological civilization. The current marine ecological classification and zoning in China comprehensively sorts out the types and natural geographical characteristics of marine ecosystems, divided the Chinese seas and adjacent waters into several levels of ecological spatial units according to different scales, effectively characterizes the geographical distribution features of marine biological communities and their habitats, and provides effective support for ecosystem based marine management. This study analyzed the practical significance of marine ecological classification and zoning. Based on a review of the development of marine ecological classification and zoning, this …

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.