Genetics Commons^™

Toward Interpretable Multi-Omics Multimodal Biomedical Artificial Intelligence, Yanjun Lyu

Computer Science and Engineering Dissertations

The complexity of human disease arises from biological processes that unfold across multiple scales, from molecular variation through cellular function, tissue organisation, brain phenotypes, each of which is associated with distinct measurement modalities, regularities, and characteristic. Contemporary biomedical artificial intelligence has brought the opportunity to reveal the complexity with in; however, its methodological default, in which models are trained on most readily available modality, does not adequately engage with the multi-scale connected structure by which biological meaning is constituted. The research area of multi-omics and multi-modal AI for biomedicine remains at an early exploratory stage, and the work presented in …

Using Rattlesnake Venom To Model Complex Trait Evolution Across Ecological And Evolutionary Scales, Samuel R. Hirst

USF Tampa Graduate Theses and Dissertations

A central challenge in evolutionary biology is understanding how genetic variation leads to phenotypicdiversity, particularly for complex traits that strongly influence fitness. Traits form the substrate of natural selection, but it is genes, that are inherited across generations. To fully understand the evolutionary process, we must therefore connect the molecular basis of trait variation with the evolutionary outcomes of such traits.

For relatively simple traits, the genotype–phenotype relationship is well understood. Classic systems, such as coat color in beach mice or toxin resistance in garter snakes, have provided effective examples of how relatively few loci underlie conspicuous adaptive differences across …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

Multi-Locas Gwas Mapping And Candidate Gene Analysis Of Anticancer Peptide Lunasin In Soybean (Glycine Max L. Merr), Rikki Locklear, Jennifer Kusumah, Layla Rashad, Felicia Lugaro, Sonia Viera, Nathan Kipyego, Faith Kipkosgei, Daisy Jerop, Shirley Jacquet, Mythy Addelmajid Kassem, Jiazheng Yuan, Elvira De Mejia, Rouf Mian

Biological Sciences Faculty Publications

Soybean (Glycine max) peptide lunasin exhibits significant cancer-preventive, antioxidant, and hypocholesterolemic effects. This study aimed to identify quantitative trait nucleotides (QTNs) associated with lunasin content and to annotate the candidate genes in the soybean genome. The mapping panel of 144 accessions was gathered from the USDA Soybean Germplasm Collection, encompassing diverse geographical origins and genetic backgrounds, and was genotyped using SoySNP50K iSelect Beadchips. The lunasin content in soybean seeds was measured using the enzyme-linked immunosorbent assay (ELISA) method, with lipid-adjusted soybean flour prepared from seeds obtained from the Germplasm Resource Information Network (GRIN) of USDA-ARS in 2003 and …

Impacts Of Multiple Coastal Stressors Across Life-History Stages In The Eastern Oyster, Amaelia Zyck

Open Access Dissertations

Urbanized estuaries are characterized as a complex of biotic and abiotic stressors, which currently challenge marine life and are expected to intensify and become increasingly unpredictable under the ongoing impacts of climate change. The persistence of coastal species that inhabit these stressful environments will ultimately depend on their ability to adapt. Many of these species have complex life cycles, featuring distinct morphological and physiological developmental stages that can exhibit unique responses to environmental pressures. However, since all stages share the same genome, selective pressures acting on one stage can have cascading effects throughout the life cycle. The larval stage, being …

Project Give: Using A Virtual Genetics Service Platform To Reduce Health Inequities And Improve Access To Genomic Care In An Underserved Region Of Texas, Blake Vuocolo, Roberta Sierra, Daniel Brooks, Christopher Holder, Lauren Urbanski, Keila Rodriguez, Jose David Gamez, Surya Narayan Mulukutla, Ana Hernandez, Alberto Allegre, Humberto Hidalgo, Sarah Rodriguez, Sandy Magallan, Jeremy Gibson, Juan Carlos Bernini, Melanie Watson, Robert Nelson, Lizbeth Mellin-Sanchez, Nancy Garcia, Lori Berry, Hongzheng Dai, Claudia Soler-Alfonso, Kent Carter, Brendan Lee, Seema R Lalani

Faculty, Staff and Students Publications

BACKGROUND: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of …

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 …

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 …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Exploring Genomic Convergence For Adaptations To Freezing Environments In Polar Fish, Ethan Talley

Biological Sciences Undergraduate Honors Theses

Convergent evolution provides valuable insights into how natural selection shapes species traits. Genomic analysis of lineages that display convergent traits has the potential to identify candidate genes for environmental adaptations across the scope of entire genomes. One remarkable example of convergent evolution is the independent development of antifreeze proteins (AFPs) in phylogenetically distant polar fish lineages. While AFPs themselves are relatively well studied, the full genomic context of adaptation to freezing conditions in these fish lineages remains largely unexplored. Leveraging the whole genome sequences previously assembled in our lab, along with other high-quality genomes available in GenBank, I examined the …

Understanding The Origin Of Parthenogenesis Via Crossing And Crispr Gene Editing In Daphnia Pulex, Thinh Pham

Biology Dissertations - Archive

Daphnia has been used as a key model system for studying ecological changes, evolution, and genomics for the past few decades due to its rapid turnover time in reproduction. The organism possesses two fascinating modes of reproduction: obligate parthenogenesis and cyclical parthenogenesis. This dissertation delves into the intricate reproductive strategies of Daphnia pulex, focusing on hybrid F1s from different reproductive modes. The first aim is to investigate 31 hybrid F1s generated from obligate parthenogenesis (OP) and cyclical parthenogenesis (CP) parental lines. Transcriptomic analysis reveals misexpression patterns and regulatory divergences, highlighting meiosis-related genes like CDC6 as potential parthenogenesis regulators. The …

The Detection Of Putative Recessive Lethal Haplotypes In Irish Sheep Populations, Rory Mcauley

ORBioM (Open Research BioSciences Meeting)

In livestock populations, recessive lethal alleles are a known contributor to poor reproductive performance due to embryonic death in homozygous individuals. Despite their lethal effect in the recessive form, these alleles may be maintained at high frequencies among carrier animals because of their positive pleiotropic effects on economically important traits. Although several such recessive alleles have been identified in cattle and pig populations, limited studies have been completed in sheep, and none within Irish sheep populations. Genotype data for 69,034 animals from five major Irish sheep breeds genotyped on a variety of panels was available for this study. Only animals …

A Multicenter Analysis Of Abnormal Chromosomal Microarray Findings In Congenital Heart Disease, Benjamin J Landis, Lindsey R Helvaty, Gabrielle C Geddes, Jiuann-Huey Ivy Lin, Svetlana A Yatsenko, Cecilia W Lo, William L Border, Stephanie Burns Wechsler, Chaya N Murali, Mahshid S Azamian, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L Mcbride, Jennelle C Hodge, Stephanie M Ware

Faculty, Staff and Students Publications

Background

Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype–phenotype relationships.

Methods and Results

Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per …

Genotype Error Due To Low-Coverage Sequencing Induces Uncertainty In Polygenic Scoring, Ella Petter, Yi Ding, Kangcheng Hou, Arjun Bhattacharya, Alexander Gusev, Noah Zaitlen, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Polygenic scores (PGSs) have emerged as a standard approach to predict phenotypes from genotype data in a wide array of applications from socio-genomics to personalized medicine. Traditional PGSs assume genotype data to be error-free, ignoring possible errors and uncertainties introduced from genotyping, sequencing, and/or imputation. In this work, we investigate the effects of genotyping error due to low coverage sequencing on PGS estimation. We leverage SNP array and low-coverage whole-genome sequencing data (lcWGS, median coverage 0.04×) of 802 individuals from the Dana-Farber PROFILE cohort to show that PGS error correlates with sequencing depth (p = 1.2 × 10

Anything But Bland: Uncovering The Hidden Diversity And Genomic Origin Of The Threatened Vanilla Spice, Paige Ellestad

Boise State University Theses and Dissertations

Conserving the genetic diversity of crop species and their wild relatives has become a mounting concern as the detrimental effects of climate change, habitat destruction, and genetic erosion are being realized. In this epoch of unprecedented biodiversity loss, the genetic resources needed to improve crops may be at risk of extinction. Even one of the most iconic spices, vanilla, is threatened. Wild populations of the main vanilla producing species, Vanilla planifolia Andrews (Orchidaceae), are being rapidly extirpated due to deforestation and illegal harvesting in their native range. On top of that, clonal propagation methods within cultivated plants are hypothesized to …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …

Assessing Genomic Literacy In Advanced Practice Nursing Students Before And After An Intervention, Guiselle Palomera

Doctor of Nursing Practice Final Manuscripts

Introduction

The purpose of this evidence-based Doctor of Nursing Practice (DNP) project was to examine genetics and genomics literacy in advanced practice nursing students before and after an intervention.

Background

As genomics continue to play an emerging role in healthcare, and advancements are introduced into clinical practice, it is critical that nurses be competent in genetics and genomics concepts. There is a fundamental need to incorporate genomics education into nursing school curriculum. However, studies have shown that the majority of faculty across nursing schools in the United States are ill-equipped to teach genetics and genomics concepts. Furthermore, many interventions to …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).

The Evolutionary Causes And Consequences Of Mammalian Hybridization, Kelsie E. Hunnicutt

Electronic Theses and Dissertations

The natural recombination of divergent genomes within hybrid offspring provides windows through which we can study evolutionary processes and the dynamics of speciation. In this work, I use a combination of comparative and population genomics on both laboratory crosses of divergent rodent lineages and a hybrid zone of cottontail rabbits in the wild to study the causes and consequences of hybridization in mammals. Hybrid sterility is a common reproductive barrier between species that tends to preferentially manifest in the heterogametic sex and frequently genetically maps to the sex chromosomes. Thus, the sex chromosomes appear to play a special role in …

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 …

Riverscape Community Genomics Of Ozark Fishes: A Comparative Framework To Infer Ecological And Evolutionary Determinants Of Genetic Diversity, Zachery D. Zbinden

Graduate Theses and Dissertations

Genetic variation is a crucial component of biodiversity and represents the variability and spatial structure of alleles within and among organisms. Evolution modulates this variability over time through mutation, selection, gene flow, and genetic drift. However, our capacity to test foundational theories of population genetics has always been at the mercy of molecular approaches available to quantify patterns of genetic diversity. Initially, techniques for empirical DNA studies were in their infancy and limited by technologies and the price per unit of genetic information. Because of these constraints, our pursuits have generally been limited to investigations of one or a few …

Strategic Plan For Genomic Competencies Into Undergraduate Nursing Curriculum, Myerann Royce M. Mangalino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Problem: As genomics research continues to grow in medicine and in popular culture, an educational gap in nursing is inevitable. Nurses must have a strong understanding of genetics and genomics to effectively integrate them into current practice.Objectives: The objective is to identify gaps in the current undergraduate curriculum and build threads that may be incorporated into the current curriculum to fill the identified gaps. Methods: The foundation of this project was the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators, 2nd Edition (Consensus Panel on Genetic/Genomic Nursing Competencies, 2008). A strategic plan was created to increase …

Genetics And Genomics Education Among Physician Assistants, Wesley Patterson

All Dissertations

This dissertation comprises five chapters to describe genetics and genomics education among physician assistant/associate (PA) students and practicing PAs. Chapter I introduces the gap in supply and demand of genetic services, the need for non-genetics healthcare providers to fill the gap, and the PA profession as a solution.

Chapter II is a rapid literature review that summarizes the available literature regarding genetics and genomics education for PAs. A paucity of literature exists to describe the current state of PA genetics-genomics education. The few studies retrieved describe content being taught in PA programs, the number of genetics-genomics contact hours PA students …

Single Cell Lineage Tracing Reveals Mechanisms Of Tumor Initiation And Chemoresistance In Small Cell Lung Cancer, Hannah Wollenzien

Dissertations and Theses

Small Cell Lung Cancer (SCLC) is a devastating disease characterized by a very low two-year survival rate and almost universal acquisition of chemoresistance. Nearly all patients have tumors driven by functional inactivation of the tumor suppressors Rb and p53, but despite the uniform origins of this tumor, not all patients are genetically or phenotypically identical. SCLC can be subtyped into four unique molecular subtypes, determined by the expression of ASCL1, NEUROD1, POU2F3, or YAP1. These subtypes are plastic, and subtype switching after chemotherapy has been documented. Without the understanding of how tumor heterogeneity arises, we cannot solve the challenge of …

Composition And Homology In The Taxonomic Classification Of Escherichia Coli, Tanya Irani

Theses and Dissertations (Comprehensive)

As new techniques have been introduced, specifically the possibility of complete genome sequencing, better methods of defining bacterial species have also been proposed. One of the most recently proposed methods, using bioinformatic techniques, is to calculate the average nucleotide identity (ANI) between the homologous genome segments of different isolates. Another method for species discrimination that has been tested successfully is the similarity of DNA compositional signatures. However, in a recent update, DNA signatures split the available Escherichia coli complete genomes into three groups. To check if this result was consistent with such genomes belonging to different species, we tested methods …

Addressing The Issue Of Missing Heritability: The Importance Of Apoptosis In Hereditary Breast And Ovarian Cancer And Functional Assessment Of Tp53i3-S252*, Sophia Chaudhry

Wayne State University Dissertations

A quarter of all cases of ovarian cancer (OVCA) cases are due to inherited factors. However, much of the genetic risk remains unknown. We have previously established the importance of whole exome sequencing to answer the question for missing heritability. We identified clinically actionable and novel risk loci in the DNA repair and cell cycle regulation pathways by assessing a cohort of women diagnosed with OVCA, wildtype for BRCA1/BRCA2 and suspected to be hereditary due to family history of breast cancer/OVCA. Equally as important was the exploration and discovery of novel risk loci in the apoptosis pathway. A total of …

Mixing It Up: The Impact Of Episodic Introgression On The Evolution Of High-Latitude Mesocarnivores, Jocelyn P. Colella

Biology ETDs

At high latitudes, climatic oscillations have triggered repeated episodes of organismal divergence by geographically isolating populations. For terrestrial species, extended isolation in glacial refugia – ice-free regions that enable terrestrial species persistence through glacial maxima – is hypothesized to stimulate allopatric divergence. Alternatively, upon glacial recession, divergent populations expanded from independent glacial refugia and often contacted other diverging populations. In the absence of reproductive isolating mechanisms, this biogeographic process may trigger hybridization and ultimately, gene flow between divergent taxa. My dissertation research aims to understand how these episodic periods of isolation and contact have impacted the evolution of high latitude …

Cryptic Lineages And A Population Damned To Incipient Extinction? Insights Into The Genetic Structure Of A Mekong River Catfish, Amanda S. Ackiss, Binh T. Dang, Christopher E. Bird, Ellen E. Biesack, Phen Chheng, Latsamy Phounvisouk, Quyen H.D. Vu, Sophorn Uy, Kent E. Carpenter

Biological Sciences Faculty Publications

An understanding of the genetic composition of populations across management boundaries is vital to developing successful strategies for sustaining biodiversity and food resources. This is especially important in ecosystems where habitat fragmentation has altered baseline patterns of gene flow, dividing natural populations into smaller sub-populations and increasing potential loss of genetic variation through genetic drift. River systems can be highly fragmented by dams built for flow regulation and hydropower. We used reduced-representation sequencing to examine genomic patterns in an exploited catfish, Hemibagrus spilopterus, in a hotspot of biodiversity and hydropower development- the Mekong River basin. Our results revealed the …

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 …