Genetics and Genomics Commons^™

Robust Sex Determination In The Caenorhabditis Nigoni Germ Line, Jonathan P Harbin, Yongquan Shen, Shin-Yi Lin, Kevin Kemper, Eric S Haag, Erich M Schwarz, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sexual characteristics and reproductive systems are dynamic traits in many taxa, but the developmental modifications that allow change and innovation are largely unknown. A leading model for this process is the evolution of self-fertile hermaphrodites from male/female ancestors. However, these studies require direct analysis of sex-determination in male/female species, as well as in the hermaphroditic species that are related to them. In Caenorhabditis nematodes this has only become possible recently, with the discovery of new species. Here, we use gene editing to characterize major sex-determination genes in C. nigoni, a sister to the widely studied hermaphroditic species C. briggsae. These …

The Roles Of Cup1, Ssu1, And Mitochondrial Dna In Copper Tolerance In Wild Yeasts, Madeleine Panek

Undergraduate Honors Theses

Understanding the genetic basis of complex traits remains a central challenge in biology. In Saccharomyces cerevisiae, copper resistance is a multifactorial trait shaped by both genetic and environmental influences, yet its underlying mechanisms are not fully understood. The genes CUP1 and SSU1 are known to influence copper resistance, though how these genes interact with each other and with mitochondrial DNA (mtDNA) variation in wild yeast populations is unknown. I hypothesized that the genes CUP1 and SSU1 and variation in mtDNAs contribute to copper resistance in wild yeasts independently and through genetic interactions. To test this, I measured copper resistance …

Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh

Computer Science ETDs

Advancing personalized medicine depends on effectively integrating and interpreting the vast, heterogeneous landscape of biological data, from genomic sequences and transcriptomics to the insights embedded in scientific literature. Current machine learning models often focus on single data modalities, limiting their capacity to capture the multifaceted nature of biological systems. We address this gap by developing three attention-based machine-learning models integrating diverse data modalities. Firstly, DeepVul is a multi-task model that leverages cancer transcriptome data to predict genes critical for cancer survival and their corresponding drugs. Subsequently, LitGene refines gene representations by integrating textual information from the scientific literature. Finally, Protein2Text …

Effectiveness Of Silvicultural Options In Renewal Of Trembling Aspen–Jack Pine Mixedwood Stands, 21 Years After Treatment, Rongzhou Man

Aspen Bibliography

Regenerating conifers after harvest through planting and postharvest broadcast application of herbicide is effective in ensuring the survival and growth of seedlings, but faces challenges in meeting broad social and ecological objectives of forest management. This study reports the effectiveness of alternative options in regenerating jack pine (Pinus banksiana Lamb.), 21 years after harvest of trembling aspen (Populus tremuloides Michx.)-dominated boreal mixedwood stands. The treatment options included (i) preharvest spray—aerial broadcast spray prior to harvest, (ii) postharvest partial spray—ground herbicide application in strips, (iii) partial harvest in strips, (iv) postharvest aerial broadcast, and (v) uncut reference. Twenty-one years …

Missense Mutation Of Msh6 Leucine 696 Has No Apparent Effect On The Dna Mismatch Repair Process, Razan H. Hammad, Rafia Rashid, Essence Tarrence, Christopher Bolden, Joanna E. Haye-Bertolozzi

XULAneXUS

Lynch Syndrome and Constitutional Mismatch Repair Deficiency are human diseases implicated in mutations of DNA mismatch repair (MMR) genes. This experiment tested a mutation of an MMR gene, MSH6, and evaluated how the mutation affected overall MMR effectiveness. Using the yeast Saccharomyces cerevisiae, we performed the CAN1 forward mutation assay to study msh6-L696F and its implications in the MMR process. We hypothesized that there would be a significant change in molecular function in the Msh6 protein in the presence of this mutation. Bioinformatic tools predicted that this amino acid change would have deleterious effects on MMR function. However, …

Life After Death: Investigating The Resistance And Recovery Of Fungal Communities To Foundation Tree Mortality, Jessie F. Marlenee

Biology ETDs

Tree mortality can have cascading effects on the composition and resilience of interacting fungal communities. Yet, little is known about the impact tree mortality, distinct from abiotic drivers (i.e., drought), has on these communities. This dissertation focuses on the resilience of fungal communities to experimental tree mortality in a piñon-juniper woodland. In chapter one, I found that piñon mortality reduced piñon fine root biomass and piñon mycorrhizal fungal diversity, whereas juniper mycorrhizal fungi were unaffected by juniper mortality. In chapter two, I revealed that piñon mortality altered the composition and spatial structure of mycorrhizal and saprotrophic fungi in the soil, …

The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe

Department of Nutrition Student Projects

Paternal obesity is a rising concern in conception and reproductive health, with increasing evidence suggesting its impact on pregnancy outcomes. While maternal obesity's effects on fetal development and placental function are well-documented, the role of paternal obesity remains less understood. The placenta, crucial for nutrient exchange and fetal development, can be disrupted by inflammation, oxidative stress, and epigenetic modifications, potentially leading to long-term health implications for both maternal and fetal health. Understanding the paternal influence on placental development is essential for improving pregnancy outcomes and offspring
health. This study aims to investigate the relationship between paternal obesity on placental function …

Genome Analysis Of Aeromonas Hydrophila Strain S14-452, Zarin Tasnim Raya

Undergraduate Research Conference

The Aeromonas hydrophila are gram-negative, opportunistic bacteria that can infect many groups of organisms, mainly fish and amphibians. In channel catfish, A. hydrophila causes fatal bacterial septicemia, leading to massive economic losses for catfish farmers. Therefore, an understanding of its genome will aid in identifying its virulence factors, metabolic pathways and survival mechanisms within the host. This study details the draft genome sequence of A. hydrophila strain S14-452, isolated from channel catfish exhibiting bacterial septicemia during a disease outbreak at a catfish farm.

A. hydrophila strain S14-452 was sequenced using the Illumina iSeq 100 System. Assembly was performed with SPAdes, …

Large-Scale Multi-Omics Analyses In Hispanic/Latino Populations Identify Genes For Cardiometabolic Traits, Lauren E. Petty, Hung-Hsin Chen, Elizabeth G. Frankel, Wanying Zhu, Carolina G. Downie, Mariaelisa Graff, Phillip Lin, Priya Sharma, Ravi Duggirala, John Blangero

Human Genetics Publications

Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with …

Hierarchical Lineage Tracing To Unravel Mechanisms Of Cancer Treatment Resistance, Rachel Danielle Saxe

Dartmouth College Ph.D Dissertations

Cancer cells adapt to treatment, leading to the emergence of clones that are more aggressive and resistant to anti-cancer therapies. We have a limited understanding of the development of treatment resistance as we lack technologies to map the evolution of cancer under the selective pressure of treatment. To address this, we developed a hierarchical, dynamic lineage tracing method called FLARE (Following Lineage Adaptation and Resistance Evolution). We use this technique to track the progression of acute myeloid leukemia (AML) cell lines through exposure to Cytarabine (AraC), a front-line treatment in AML, in vitro and in vivo. We map distinct cellular …

Whole Genome Sequencing Analysis Of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele, Xinruo Zhang, Jennifer A. Brody, Mariaelisa Graff, Heather M. Highland, Nathalie Chami, Hanfei Xu, Zhe Wang, Kendra R. Ferrier, John Blangero, Joanne E. Curran

School of Medicine Publications

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P <  5 × 10−9), including two secondary signals. Notably, we identified and replicated a novel low-frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD …

Determining The Kinetic Basis Of Crispr-Cas12a2 Function, Sobita Kunwar, Thomson Hallmark, Dylan Keiser, Bronson Naegle, Sudeshna Manna, Aaron Thomas, Chase L. Beisel

Student Research Symposium

CRISPR- Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated) systems are bacterial adaptive immune systems that protect bacteria against mobile genetic elements such as viruses and plasmids^1,2.

Creating A Stat2 Knock-Out Rat With Crispr/Cas9 Using I-Gonad, Isabella Dejesus, Yanan Liu, Don Joo, Nathan Merrill

Student Research Symposium

The STAT2 gene encodes a protein called Signal Transducer and Activator of Transcription 2. This protein is a part of the STAT family of transcription factors, which are involved in mediating cellular responses to various cytokines and growth factors, particularly those related to the immune response. Here, we established a successful procedure for creating a STAT2 knock-out (KO) Rat that can be used for more accurate disease testing of serious human ailments such as Lupus, Polio, Herpes, RSV, and even cancer.

Disentangling Effects Of The Dr And Dq Isomers Encoded By The Hla Class Ii Haplotype Drb1*15:01/Dqb1*06:02 To Help Establish The True Risk Allele For Fviii Inhibitor Development In Hemophilia A, Vincent P. Diego, Bernadette W. Luu, Marcio A. Almeida, Jacob Galan, Eron G. Manusov, Juan M. Peralta, Satish Kumar, Joanne E. Curran, Harald H. H. Goring, Sarah Williams-Blangero, John Blangero, Tom Howard

School of Medicine Publications

Introduction: Hemophilia A (HA) patients (HAPs) with the human leukocyte antigen (HLA)-class-II (HLAII) haplotype DRB1*15:01/DQB1*06:02, and thus antigen presenting cells which express HLAII β-polypeptide chains that form heterodimers of DR15- and DQ6-serotypes, respectively, have an increased risk of developing factor (F)VIII inhibitors (FEIs)—neutralizing antibodies against the therapeutic-FVIII-proteins (tFVIIIs) infused to prevent/arrest bleeding. As DRB1*15:01 and DQB1*06:02 exist in strong linkage disequilibrium, association analysis cannot determine which is the actual risk allele.

Methods: To establish the true risk allele of this haplotype, we analyzed the tFVIII-derived peptides (tFVIII-dPs) bound to either the DR or DQ molecules that comprise the individual HLAII …

Discovery Of Suitable Habitat For Freshwater Mussel Species In The Appomattox River Through The Use Of Environmental Dna., Nicholas Duellman

Longwood Senior Thesis Proposal

Freshwater mussels are a keystone species providing crucial ecosystem services and river composition resiliency. Anecdotal evidence suggests the presence of freshwater mussels within the Appomattox river, the specifics of population sizes and suitable habitat remains an open question. Environmental DNA (eDNA) usage in conservation ecology has exploded in use within the past two decades, being far less invasive and cost-demanding than traditional methods. An eDNA metabarcoding pipeline of the 16s mitochondrial ribosomal subunit was built in R v. 4.4.2, using dada2 v. 3.2.1 package to trim MinION single read ASV outputs for freshwater mussel species identification in the interest of …

Analysis Of Chromatin Accessibility Changes In Endothelial Cells Exposed To Plastic Contaminants, Mikhail Y. Salnikov, Carly Boye, David B. Witonsky, Gabrielle Garlicki, Adnan Alazizi, Francesca Luca, Roger Pique-Regi

Medical Student Research Symposium

Degradation products from everyday plastic products are known to bioaccumulate and have also been shown to contaminate drinking water and food sources. BPA and phthalates are endocrine disrupting chemicals and plastic components that have previously been associated with endothelial cell dysfunction, atherosclerotic and other adverse cardiovascular events. However, there is a limited understanding of the mechanisms underlying these associations, such as genome-wide chromatin accessibility changes in endothelial cells exposed to these compounds. The purpose of this study is to explore genome-wide changes in chromatin accessibility associated with plastic exposure, as well as the discovery of transcription factor binding motifs dysregulated …

Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo

Medical Student Research Symposium

Endometrial cancer is rising in incidence in the United States, notably among premenopausal women. This increase and the trend of delayed childbearing warrant the need for further advancement in fertility-sparing treatment for endometrial cancer. A gene left widely unexplored in its possible clinical utility as a target for fertility-sparing treatment is KMT2D, a lysine-specific methyltransferase and tumor suppressor. Preliminary gene set enrichment analysis on a 12Z endometriotic epithelial cell line identified TIMP3 as a gene that is possibly regulated by KMT2D expression. TIMP3 encodes an irreversible inhibitor of matrix metalloproteinases (MMPs), a well-recognized class of proteins as contributing to the …

Fisheries Management Paper No.286: Western Australian Octopus Resource Harvest Strategy, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

Harvest strategies for Western Australia’s (WA) aquatic resources are formal documents developed to support decision-making processes that ensure the outcomes are consistent with the principles of Ecologically Sustainable Development (ESD; Fletcher 2002a) and Ecosystem Based Fisheries Management (EBFM; Fletcher et al. 2012). Harvest strategies are a key component of all contemporary fishery management systems and a requirement for certification under the Marine Stewardship Council (MSC). The objectives of ESD are reflected in the objectives of the Fish Resources Management Act 1994 (FRMA).

This Octopus Resource Harvest Strategy (Harvest Strategy) has been developed and revised in line with the Harvest Strategy …

Focal Adhesion Genes And Proteins Are Differentially Expressed Across Cell Types In Down Syndrome, Brian Yoon

Senior Theses

Down syndrome (DS), caused by an extra copy of chromosome 21, leads to widespread gene expression changes through mechanisms such as transcriptional dysregulation and altered protein interactions. These disruptions contribute to a range of clinical features, including impaired wound healing, immune dysfunction, and neurodevelopmental abnormalities. This study focused on how DS affects fibroblast morphology and motility—processes critical for tissue repair and brain development. Using quantitative immunocytochemistry and image analysis, we found that DS fibroblasts displayed a broader, less polarized shape, with increased cell perimeter and reduced aspect ratio. However, levels of key adhesion proteins like vinculin, FAK, and β-actin were …

Examining Genomic Islands To Trace The Evolution Of The Urinary Microbiome, Elena G. Renshaw

Senior Theses

There has been a longstanding misconception that the healthy human urinary tract is sterile; however, increasing evidence demonstrates the presence of a dynamic resident urinary microbiota. Emerging research suggests that the urinary microbiota plays a protective role against urological symptoms and infection, but interactions between urinary bacterial species remain understudied. Genomic islands (GIs) are large DNA segments acquired through horizontal gene transfer between bacteria and can provide fitness advantages, particularly to uropathogens. This research utilizes 1,301 genome sequences isolated from urine samples representing the bacterial diversity found within the human urinary tract. GIs were annotated using IslandViewer 4 and TreasureIsland. …