Genetics and Genomics Commons^™

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Soybean Genetics, Genomics, And Breeding For Improving Nutritional Value And Reducing Antinutritional Traits In Food And Feed, William M. Singer, Yi-Chen Lee, Zachary Shea, Caio Canella Vieira, Dongho Lee, Xiaoying Li, Mia Cunicelli, Shaila S. Kadam, Mohammad Amir Waseem Khan, Grover Shannon, M. A. Rouf Mian, Henry T. Nguyen, Bo Zhang

Agriculture Faculty Publications

Soybean [Glycine max(L.) Merr.] is a globally important crop due to its valuable seed composition, versatile feed, food, and industrial end-uses, and consistent genetic gain. Successful genetic gain in soybean has led to widespread adaptation and increased value for producers, processors, and consumers. Specific focus on the nutritional quality of soybean seed composition for food and feed has further elucidated genetic knowledge and bolstered breeding progress. Seed components are historical and current targets for soybean breeders seeking to improve nutritional quality of soybean. This article reviews genetic and genomic foundations for improvement of nutritionally important traits, such as protein and …

Genetic Determinants Underlying The Progressive Phenotype Of Β-Lactam/Β-Lactamase Inhibitor Resistance In Escherichia Coli, William C Shropshire, Hatim Amiji, Jordan Bremer, Selvalakshmi Selvaraj Anand, Benjamin Strope, Pranoti Sahasrabhojane, Marc Gohel, Samuel Aitken, Sarah Spitznogle, Xiaowei Zhan, Jiwoong Kim, David E Greenberg, Samuel A Shelburne

Faculty, Staff and Student Publications

Currently, whole-genome sequencing (WGS) data have not shown strong concordance with Escherichia coli susceptibility profiles to the commonly used β-lactam/β-lactamase inhibitor (BL/BLI) combinations: ampicillin-sulbactam (SAM), amoxicillin-clavulanate (AMC), and piperacillin-tazobactam (TZP). Progressive resistance to these BL/BLIs in the absence of cephalosporin resistance, also known as extended-spectrum resistance to BL/BLI (ESRI), has been suggested to primarily result from increased copy numbers of bla TEM variants, which is not routinely assessed in WGS data. We sought to determine whether addition of gene amplification could improve genotype-phenotype associations through WGS analysis of 147 E. coli bacteremia isolates with increasing categories of BL/BLI non-susceptibility ranging …

Combined Purebred And Crossbred Genetic Evaluation Of Columbia, Suffolk, And Crossbred Lamb Birth And Weaning Weights: Systematic Effects And Heterogeneous Variances, Napoleón Vargas Jurado, David R. Notter, Joshua B. Taylor, Daniel J. Brown, Michelle R. Mousel, Ronald M. Lewis

Department of Animal Science: Faculty Publications

Despite the benefits of crossbreeding on animal performance, genetic evaluation of sheep in the U.S. does not directly incorporate records from crossbred lambs. Crossbred animals may be raised in different environments as compared to purebreds. Systemic factors such as age of dam and birth and rearing type may, therefore, affect purebred and crossbred performance differently. Furthermore, crossbred performance may benefit from heterozygosity, and genetic and environmental variances may be heterogeneous in different breeds and their crosses. Such issues must be accounted for in a combined (purebred and crossbred) genetic evaluation. The objectives of this study were to i) determine the …

Allelic Strengths Of Encephalopathy-Associated Uba5 Variants Correlate Between In Vivo And In Vitro Assays, Xueyang Pan, Albert N Alvarez, Mengqi Ma, Shenzhao Lu, Michael W Crawford, Lauren C Briere, Oguz Kanca, Shinya Yamamoto, David A Sweetser, Jenny L Wilson, Ruth J Napier, Jonathan N Pruneda, Hugo J Bellen

Faculty, Staff and Students Publications

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype–phenotype relationships …

Using In Silico Tools To Analyze The 5ʹ Untranslated Regions Of The Alcohol Dehydrogenase Gene From Arabidopsis Thaliana And Omega Sequence, Reza Mohammadhassan, Tina Asadishad

Makara Journal of Science

The 5ʹ ends of protein-encoding genes contain 5ʹ untranslated regions (5ʹUTRs), which can effectively participate in regulating gene expression. The 5ʹUTRs of Arabidospis thaliana–derived alcohol dehydrogenase gene (AtADH) and omega (Ω) sequence from tobacco mosaic virus (TMV) are the most effective enhancers in biotechnology. In this study, bioinformatics techniques were employed to analyze the characteristics of the above sequences. After 5ʹUTR sequence collection, the inner ribosome entrance sites; small RNA (sRNA) target sequences; nucleotide contents; and upstream start and stop codons, ORFs, and coding DNA sequences of the Ω sequence and AtADH 5ʹUTR were identified. Moreover, the …

Investigating The Impact Of Transcription On Mutation Rates, Sarah Patterson

Theses and Dissertations

tRNA genes are highly transcribed and perform one of the most fundamental cellular functions. Although a universal pattern observed across all three domains of life is that highly transcribed genes tend to evolve slowly, tRNA genes have been shown previously to evolve rapidly. This rapid sequence evolution could result from relaxed selection, increased mutation rate, or a combination of both. Here, we use mutation-accumulation line sequencing data to show that tRNA genes accumulate more mutations than other gene types. Our results indicate that this elevated mutation rate is a consequence of both elevated transcription-associated mutagenesis and a lack of transcription-coupled …

A Timeline Of Klinefelter’S Syndrome, Xxy, Emma Chevalier, Tyler Venegas, Mary Salibi

Undergraduate Research Symposium Posters

Klinefelter Syndrome (KS) is a non-mendelian chromosomal disorder consisting of supernumerary X chromosomes in males, 80% of which manifest as the 47,XXY karyotype. The resulting gene dosage abnormalities affect both cognitive and physical development, with variable expressivity. The disease was first described by Harry Klinefelter in 1942 and was thought to be an endocrine disorder until the late 1950s, when karyotyping of affected individuals revealed an extra X chromosome.

(It is the most common sex chromosome aneuploidy (1:500 males) and the most common cause of azoospermia. The phenotype for KS is highly contested due to its extremely variable expressivity and …

A Genetic Screen For Metabolic Modulators In Drosophila Melanogaster, Victoria Campos, Logan Kazimer, Brandon Polimeni, Katelyn Niswonger, Matthew Meiselman

Undergraduate Research Symposium Posters

When environments become unfavorable, to preserve energy, animals will attenuate reproduction and limit growth. This evolutionary strategy requires perceiving and assessing a complex environment, a long-standing role of the nervous system. However, the nervous system’s control over endocrine states remains a monumental challenge. Here, we propose to exploit the genetic accessibility and cellular resolution readily found in Drosophila melanogaster, to fully explore how the brain controls metabolic and reproductive states. This project relies on the Meiselman Lab’s established unbiased neural activation screen, which located new neural circuits that participate in metabolic control. The project proposes the use of the split …

Towards Understanding The Interactions Between Ospreys And Human-Made Structures In The Tennessee River Valley, Natasha Karina Murphy

Theses and Dissertations

Raptor nests on human-built structures represent a significant source of conflict as they can result in bird mortality, fires, structure damage, service distribution, or power outages when falling nest materials or animals connect with energized conductors. Power companies, such as the Tennessee Valley Authority (TVA), wish to mitigate these conflicts to avoid service disruptions. In this dissertation, I present my work towards understanding and mitigating the interactions between Ospreys (Pandion haliaetus) and human-made structures. To achieve this, I explored multiple elements of conflict identification, monitoring, and basic ecology of the target species to better inform conflict mitigation. In Chapter I, …

Increased Coding Potential Of Bovine Herpesvirus 1, Victoria Jefferson

Theses and Dissertations

Bovine respiratory disease (BRD) costs the cattle industry millions of dollars in costs in treatment and loss every year in the United States. A significant pathogen often contributes to BRD is Bovine Herpesvirus 1 (BoHV-1), a double stranded DNA virus with the ability to establish latency in the trigeminal ganglia and neurons. Primary infection with BoHV-1 results in immunosuppression that increases the risk of secondary bacterial infection and pneumonia. Because herpesviruses infect their hosts for life and can be reactivated in times of stress, BoHV-1 can present a recurring risk of BRD. The following research aims to expand the knowledge …

Nicotinic Acetylcholine Receptor Signaling Maintains Epithelial Barrier Integrity, Nadja S Katheder, Kristen C Browder, Diana Chang, Ann De Maziere, Pekka Kujala, Suzanne Van Dijk, Judith Klumperman, Tzu-Chiao Lu, Hongjie Li, Zijuan Lai, Dewakar Sangaraju, Heinrich Jasper

Faculty, Staff and Students Publications

Disruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung, and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases. The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen in

Rab1a Haploinsufficiency Phenocopies The 2p14-P15 Microdeletion And Is Associated With Impaired Neuronal Differentiation, Jonathan J Rios, Yang Li, Nandina Paria, Ryan J Bohlender, Chad Huff, Jill A Rosenfeld, Pengfei Liu, Weimin Bi, Kentaro Haga, Mitsunori Fukuda, Shayal Vashisth, Kiran Kaur, Maria H Chahrour, Michael B Bober, Angela L Duker, Farah A Ladha, Neil A Hanchard, Kristhen Atala, Anas M Khanshour, Linsley Smith, Carol A Wise, Mauricio R Delgado

Faculty, Staff and Student Publications

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and …

Whole Genome Analysis Of Snv And Indel Polymorphism In Common Marmosets (Callithrix Jacchus), R Alan Harris, Muthuswamy Raveendran, Wes Warren, Hillier W Ladeana, Chad Tomlinson, Tina Graves-Lindsay, Richard E Green, Jenna K Schmidt, Julia C Colwell, Allison T Makulec, Shelley A Cole, Ian H Cheeseman, Corinna N Ross, Saverio Capuano, Evan E Eichler, Jon E Levine, Jeffrey Rogers

Faculty, Staff and Students Publications

The common marmoset (Callithrix jacchus) is one of the most widely used nonhuman primate models of human disease. Owing to limitations in sequencing technology, early genome assemblies of this species using short-read sequencing suffered from gaps. In addition, the genetic diversity of the species has not yet been adequately explored. Using long-read genome sequencing and expert annotation, we generated a high-quality genome resource creating a 2.898 Gb marmoset genome in which most of the euchromatin portion is assembled contiguously (contig N50 = 25.23 Mbp, scaffold N50 = 98.2 Mbp). We then performed whole genome sequencing on 84 marmosets …

Simultaneous Detection Of Methylation And Genetic Variations Of Bcr-Abl1 Gene By Nanopore Cas9-Targeted Sequencing, Shuilian Xie, Ying Yang, Junjie Zhang, Menglin Zhu, Wang Li, Mengting Li, Yijian Chen, Hailiang Li, Weidan Lun, Weelic Chong, Shaogui Wan

Department of Medicine Faculty Papers

No abstract provided.

Hnf4Α Isoforms Regulate The Circadian Balance Between Carbohydrate And Lipid Metabolism In The Liver, Jonathan R Deans, Poonamjot Deol, Nina Titova, Sarah H Radi, Linh M Vuong, Jane R Evans, Songqin Pan, Johannes Fahrmann, Jun Yang, Bruce D Hammock, Oliver Fiehn, Baharan Fekry, Kristin Eckel-Mahan, Frances M Sladek

Faculty, Staff and Student Publications

Hepatocyte Nuclear Factor 4α (HNF4α), a master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2) which drive the expression of different isoforms. P1-HNF4α is the major isoform in the adult liver while P2-HNF4α is thought to be expressed only in fetal liver and liver cancer. Here, we show that P2-HNF4α is indeed expressed in the normal adult liver at Zeitgeber time (ZT)9 and ZT21. Using exon swap mice that express only P2-HNF4α we show that this isoform orchestrates a distinct transcriptome and metabolome via unique chromatin and protein-protein interactions, including with different clock proteins at different …

Protective Responses Of The Intestinal Epithelial Cell Line Ht-29 Cells Exposed To Dephosphorylated Salmonella Flagellin [Research Note], Heyeon Baik, Jaiesoon Cho

The Philippine Agricultural Scientist

This study aimed to describe the effects of Salmonella Typhimurium flagellin (SFL) dephosphorylated by sweet potato purple acid phosphatase (PAP) on the protective responses of the intestinal epithelial cell line HT-29 cells. The enzyme was reported to display a broad substrate specificity for various organic phosphorylated conjugates and phosphoproteins. Dephosphorylation of SFL by sweet potato PAP decreased to 35% in the presence of 0.05 mM vanadate as compared with the negative control (p < 0.05). Intact SFL and the SFL treated with sweet potato PAP did not remarkably induce the activation of caspase-3 in HT-29 cells at all the tested levels of the substrate. Intact SFL maximally induced the release of IL (interleukin)-8 in HT-29 cells at 1000 ng/mL (p < 0.05). However, the SFL treated with the enzyme inhibited the release of IL-8 at over 100 ng/mL of the substrate as compared with intact SFL, resulting in an approximately 8-fold decrease even at 1000 ng/mL (p < 0.05). The SFL treated with the enzyme decreased the activation of the total ERK1/2 in the cells to 1.9 and 1.7–fold at 10 and 1000 ng/mL of the substrate, respectively, as compared with intact SFL (p < 0.05). In conclusion, sweet potato PAP could be a promising tool for controlling excessive inflammation during Salmonella infection in animal husbandry, and the enzyme could be a safe alternative that can overcome the drawbacks of chemotherapy.

Identification And Characterization Of Geotrichum Candidum Isolates From Peach With Reduced Sensitivity To Propiconazole, Sara Price

All Theses

Geotrichum candidum Link (1809) is a yeast-like fungus that causes sour rot of stone fruits, including peach (Prunus persica). The disease caused damage between 2021 and 2023 to the peach crop kept in cold storage at a commercial farm in South Carolina despite preharvest and postharvest applications of fungicides. Isolates from 41 symptomatic fruit, from a South Carolina (SC) commercial packing house, as well as other isolates obtained from South Carolina were identified to be G. candidum based on species-specific PCR amplifications of the β tubulin gene. Commonly used postharvest fungicide fludioxonil had no effect on G. candidum mycelial growth …

Seagrass Epibiont Biodiversity In The Northern Gulf Of Mexico, Kathryn Wyssmann

LSU New Orleans Theses and Dissertations

Epibionts on seagrass leaves contribute substantially to productivity and trophic interactions in seagrass ecosystems. Differences in epibiont assemblages and factors that contribute to epibiont diversity have been little studied on the seagrass Halodule wrightii in the northern Gulf of Mexico (nGoM). We used a metabarcoding approach to describe epibiont assemblages on H. wrightii leaves in four bays across the nGoM and to test whether epibiont assemblages differed spatially at local levels (within bays) or regional levels (from west to east). Furthermore, we tested if epibiont diversity was related to environmental conditions and/or seagrass productivity. Epibiont assemblages differed significantly between bays …

On The Origin And Evolution Of The Mosquito Male-Determining Factor Nix, James K. Biedler, Azedah Aryan, Yumin Qi, Aihua Wang, Ellen O. Martinson, Daniel A. Hartman, Fan Yang, Atashi Sharma, Katherine S. Morton, Mark Potters, Chujia Chen, Stephen L. Dobson, Gregory D. Ebel, Rebekah C. Kadling, Sally Paulson, Rui-De Xue, Michael R. Strand, Zhijian Tu

Entomology Faculty Publications

The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus, 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to …

Genome-Wide Significant Risk Loci For Mood Disorders In The Old Order Amish Founder Population, Elizabeth M. Humphries, Kwangmi Ahn, Rachel L. Kember, Fabiana L. Lopes, Evelina Mocci, Juan M. Peralta, John Blangero, David C. Glahn, Fernando S. Goes, Peter P. Zandi

School of Medicine Publications

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. …

Characterizing The Regulation Of Candida Albicans Hyphal Morphogenesis In The Context Of Host Macrophages, Hannah Wilson

Dissertations and Theses (Open Access)

Candida albicans is a commensal fungus that resides on the skin, mucosal surfaces, and in the gut of an estimated 80% of individuals. Though generally harmless, C. albicans is capable of causing uncomfortable mucosal infections as well as deadly disseminated infections depending on the immune status of the host. Although antifungal therapeutics exist, the mortality rate associated with disseminated disease still lingers around 50%. Further, C. albicans is the fourth most common cause of all bloodstream infections and continues to present as a major clinical issue with less than satisfactory treatment options. For this reason, it is imperative to understand …

Characterization Of Developmental Phenotypes In Zebrafish With Mutations In Mmachc, Briana Elise Pinales

Open Access Theses & Dissertations

Methylmalonic aciduria and homocystinuria, CblC type (cblC) syndrome (MIM 277400) is a genetic disorder resulting from a mutation in the MMACHC gene. This gene plays a crucial role as a chaperone in the conversion of vitamin B12 into its active form, which is essential for proper cellular metabolism. cblC syndrome is heterogenous by nature, primarily attributed to the extensive damage it causes across multiple bodily systems. In cases of early onset of cblC syndrome, patients may exhibit a diverse range of clinical symptoms including difficulties with feeding, dysmorphic features, microcephaly, brain abnormalities, hypotonia, developmental delays, and seizures. The study of …

Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Marco Galimberti, Joseph D Deak, Frank R Wendt, Arjun Bhattacharya, Dora Koller, Kelly M Harrington, Rachel Quaden, Emma C Johnson, Priya Gupta, Mahantesh Biradar, Max Lam, Megan Cooke, Veera M Rajagopal, Stefany L L Empke, Hang Zhou, Yaira Z Nunez, Henry R Kranzler, Howard J Edenberg, Arpana Agrawal, Jordan W Smoller, Todd Lencz, David M Hougaard, Anders D Børglum, Ditte Demontis, Veterans Affairs Million Veteran Program, J Michael Gaziano, Michael J Gandal, Renato Polimanti, Murray B Stein, Joel Gelernter

Faculty, Staff and Student Publications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within …

Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer, Changxin Zhong, Rongfeng Zhu, Ting Jiang, Sheng Tian, Xiaobao Zhao, Xiaoya Wan, Shilong Jiang, Zonglin Chen, Rong Gong, Linhao He, Jin-Ming Yang, Na Ye, Yan Cheng

Markey Cancer Center Faculty Publications

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the …

A Study Of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models, Tanner Wright, Tanner Wright

Dissertations and Theses (Open Access)

Arginine methylation is an essential post-translational modification (PTM) in cells. Protein arginine methyltransferase 5 (PRMT5) is the primary enzyme that catalyzes symmetric dimethyl arginine (SDMA) and requires methylosome protein 50 (MEP50) for stability and enzymatic activity which are necessary for life and development. Effector proteins bind different types of PTM’s to facilitate signaling. Staphylococcal nuclease Tudor domain containing 1 (SND1) is an effector that specifically binds SDMA via its single C-terminal Tudor domain. Both SND1 and PRMT5 have been implicated in hepatocellular carcinoma (HCC). SND1 has been confirmed as a driver of HCC using genetically engineered mouse models (GEMMs), though, …

A Double-Robust Test For High-Dimensional Gene Coexpression Networks Conditioning On Clinical Information, Maomao Ding, Ruosha Li, Jin Qin, Jing Ning

Faculty, Staff and Student Publications

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed …

Analyzing Extracellular Vesicles For Disease Monitoring In Metastatic Colorectal Cancer Patients, Vahid Bahrambeigi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Metastases are the main cause of cancer-related death, and the most frequent metastatic sites in patients with CRCs are liver and lung. To confirm the diagnosis of metastatic CRC (mCRCs) and to classify mCRCs, tumor biopsy of a suspected metastasis is often required. The consensus molecular subtype (CMS) classification which is based on gene expression profiles of CRC tumor specimens, is a predictive factor for treatment outcomes of standard chemotherapies for mCRCs. The practicality of repeated tumor biopsies for disease monitoring in mCRC patients is …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar

Graduate Doctoral Dissertations

The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …