Genetics and Genomics Commons^™

Characterization Of Cell Type-Specific Molecular Heterogeneity In Cancer Using Multi-Omic Approaches, Min Kyung Lee

Dartmouth College Ph.D Dissertations

Tumors are composed of heterogeneous cell types each with its own unique molecular profiles. Recent advances in single cell genomics technologies have begun to increase our understanding of the molecular heterogeneity that exists in tumors with particular focus on gene expression and chromatin accessibility profiles. However, due to limitations in methods for certain sample types and high cost for single cell genomics, bulk tumor molecular profiling has been and remains widely used. In addition, other facets of single cell epigenomic profiling, particularly methylation and hydroxymethylation, remains underexplored. Thus, investigations to understand the cell type specific epigenetic heterogeneity and the cooperation …

Revolutionary Advances In The Treatment Of Genetic Disease, Emma Kaitlyn Carrigan

Honors Theses and Capstones

No abstract provided.

ผลของสารสกัดสมุนไพรที่มีเห็ดกระถินพิมาน Phellinus Linteus เป็นองค์ประกอบร่วมกับซิสพลาตินต่อการมีชีวิตของเซลล์ วัฏจักรของเซลล์ อะพอพโทซิส และการแสดงออกของยีนในเซลล์มะเร็งปากมดลูก, พิลาสลักษณ์ ปานสุข

Chulalongkorn University Theses and Dissertations (Chula ETD)

มะเร็งปากมดลูกสามารถรักษาได้ด้วยเคมีบำบัดโดยใช้สารซิสพลาติน ซึ่งให้ผลข้างเคียงหลายประการ ในการรักษาทางการแพทย์แผนโบราณมีการใช้เห็ดกระถินพิมาน (Phellinus linteus) รักษาโรคมะเร็ง ซึ่งเห็ดชนิดนี้มีประสิทธิภาพในการยับยั้งเซลล์มะเร็งและส่งเสริมการตอบสนองของระบบภูมิคุ้มกัน การศึกษานี้มีวัตถุประสงค์เพื่อศึกษาผลของสารสกัดสมุนไพรที่มีเห็ดกระถินพิมานเป็นองค์ประกอบร่วมกับซิสพลาตินต่อการมีชีวิตของเซลล์วัฏจักรของเซลล์ และอะพอพโทซิสและการแสดงออกของยีน MKI67 และ CDK7 ของเซลล์มะเร็งปากมดลูก C33a และ SiHa เพื่อลดผลข้างเคียงของเคมีบำบัดของสารซิสพลาติน การทดสอบการรอดชีวิตของเซลล์ในเซลล์มะเร็งปากมดลูกด้วยวิธี MTT assay ทำให้ได้ค่าความเข้มข้นของสารสกัดสมุนไพรและซิสพลาตินที่ความเข้มข้น IC50 จากนั้นนำค่าความเข้มข้น IC50 ของสารสกัดสมุนไพรในแต่ละเซลล์ที่ได้มาใช้ร่วมกับซิสพลาติน โดยทำการลดค่าความเข้มข้นให้ต่ำลงจากค่าความเข้มข้น IC50 ผลพบว่าการใช้สารสกัดสมุนไพรและสารซิสพลาตินร่วมกันในเซลล์ C33a และ SiHa ช่วยลดปริมาณการใช้สารซิสพลาตินลง 6 – 12 เท่า และ 8 – 26 เท่า จากความเข้มข้นที่ IC50 ของสารซิสพลาติน ตามลำดับ สำหรับการทดสอบพอพโทซิสของเซลล์มะเร็ง ผลพบว่าสารสกัดสมุนไพร สารซิส-พลาติน และสารสกัดสมุนไพรร่วมกับซิสพลาตินมีการเหนี่ยวนำให้เซลล์ C33a และ SiHa เกิดการตายผ่านกลไกอะพอพโทซิส จึงทำให้เซลล์มีการสะสมอยู่ในระยะ early apoptosis และ late apoptosis ในการศึกษาวัฏจักรของเซลล์มะเร็งพบว่าสารสกัดสมุนไพรร่วมกับซิสพลาตินที่มีการเหนี่ยวนำให้เกิดการหยุดของวัฏจักรของเซลล์ที่ระยะ G2 ของเซลล์ C33a และ SiHa แต่ผลการแสดงออกของยีน MKI67 และ CDK7 ไม่ได้เป็นไปในทางเดียวกันกับผลการศึกษาข้างต้น จึงคาดว่าอาจมีการควบคุมผ่านเส้นทางอื่น อย่างไรก็ตามยังคงต้องทำการศึกษาเพิ่มเติมเพื่อค้นหากลไกการออกฤทธิ์ของสารสกัดสมุนไพรเมื่อใช้ร่วมกับซิสพลาตินต่อไป

Methylation Patterns Across Tissue Type And Time In Peromyscus Leucopus: A Targeted Museum Study, Loryn Smith

Master's Theses or Doctor of Nursing Practice

Museum specimens are a vital data source for many types of studies. One relatively new use includes studying methylation patterns. Methylation patterns are a form of epigenetics or how gene expression changes without alteration of the genetic code. These patterns have been examined in many mammals. However, the focus has previously been on overall epigenetic patterns. Few studies have investigated whether methylation patterns differ across tissue types, time, or preservation method. In this study, I compared methylation patterns in muscle, liver, toe pads, and nasal bones from Peromyscus leucopus (white-footed mouse) museum specimens collected in 2022, 2018, 2014, and 2008 …

Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme …

Biodiversity Of Philippine Marine Fishes: A Dna Barcode Reference Library Based On Voucher Specimens, Katherine E. Bemis, Matthew G. Girard, Mudjekeewis D. Santos, Kent E. Carpenter, Jonathan R. Deeds, Diane E. Pitassy, Nicko Amor L. Flores, Elizabeth S. Hunter, Amy C. Driskell, Kenneth S. Macdonald Iii, Lee A. Weigt, Jeffrey T. Williams

Biological Sciences Faculty Publications

Accurate identification of fishes is essential for understanding their biology and to ensure food safety for consumers. DNA barcoding is an important tool because it can verify identifications of both whole and processed fishes that have had key morphological characters removed (e.g., filets, fish meal); however, DNA reference libraries are incomplete, and public repositories for sequence data contain incorrectly identified sequences. During a nine-year sampling program in the Philippines, a global biodiversity hotspot for marine fishes, we developed a verified reference library of cytochrome c oxidase subunit I (COI) sequences for 2,525 specimens representing 984 species. Specimens were primarily purchased …

Adjusting For Gene-Specific Covariates To Improve Rna-Seq Analysis, Hyeongseon Jeon, Kyu-Sang Lim, Yet Nguyen, Dan Nettleton

Mathematics & Statistics Faculty Publications

Summary

This paper suggests a novel positive false discovery rate (pFDR) controlling method for testing gene-specific hypotheses using a gene-specific covariate variable, such as gene length. We suppose the null probability depends on the covariate variable. In this context, we propose a rejection rule that accounts for heterogeneity among tests by employing two distinct types of null probabilities. We establish a pFDR estimator for a given rejection rule by following Storey's q-value framework. A condition on a type 1 error posterior probability is provided that equivalently characterizes our rejection rule. We also present a suitable procedure for selecting a tuning …

Therapeutic Neutralizing Monoclonal Antibody Administration Protects Against Lethal Yellow Fever Virus Infection, Michael J. Ricciardi, Lauren N. Rust, Nuria Pedreño-Lopez, Sofiya Yusova, Sreya Biswas, Gabriela M. Webb, Lucas Gonzalez-Nieto, Thomas B. Voigt, Johan J. Louw, Fernanda D. Laurino, John R. Dibello, Hans-Peter Raué, Aaron M. Barber-Axthelm, Kimberly Chun, Samantha Uttke, Lidiane M. S. Raphael, Aaron Yrizarry-Medina, Brandon C. Rosen, Rebecca Agnor, Lina Gao, Caralyn Labriola, Michael Axthelm, Jeremy Smedley, Justin G. Julander, Myrna C. Bonaldo, Laura M. Walker, Ilhem Messaoudi, Mark K. Slifka, Dennis R. Burton, Esper G. Kallas, Jonah B. Sacha, David I. Watkins, Benjamin J. Burwitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Yellow fever virus (YFV) is a reemerging global health threat, driven by several factors, including increased spread of the mosquito vector and rapid urbanization. Although a prophylactic vaccine exists, vaccine hesitancy, supply deficits, and distribution difficulties leave specific populations at risk of severe YFV disease, as evidenced by recent outbreaks in South America. To establish a treatment for patients with severe YFV infection, we tested 37 YFV-specific monoclonal antibodies isolated from vaccinated humans and identified two capable of potently neutralizing multiple pathogenic primary YFV isolates. Using both hamster and nonhuman primate models of lethal YFV infection, we demonstrate that a …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

Molecular Genetic Studies Of Horses, Especially With Reference To Aggrecan And Dwarfism, John Edmund Eberth

Theses and Dissertations--Veterinary Science

This work consists of studies on dwarfism in Miniature horses and a study on breakdowns in Thoroughbreds in relation to gene aggrecan. A correction of the description and designation of D3 dwarf variant in aggrecan (ACAN) from the master’s thesis Chondrodysplasia-like dwarfism in the Miniature horse (2013). Commercial sequencing showed previous sequencing reads presented an artifact and not a single base deletion. Analysis showed a single base missense mutation in exon 8 identified as D3* was the actual cause. Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses by Eberth et al. (2018), corrected the …

Use Of Molecular Genetics To Investigate Population Structure And Swayback In Horses, Navid Yousefimashouf

Theses and Dissertations--Veterinary Science

The present research incorporated molecular genetic methods to 1) investigate the genetic basis of Juvenile Onset Lordosis or Swayback in the American Saddlebred horses; and 2) conduct a population genetic study to compare the Persian Kurdish, Persian Arabian and American Thoroughbred horse populations.

Juvenile-onset lordosis, or swayback, is a condition in horses where the conformational topline back curvature drops significantly within the first two years of life. The trait has a higher prevalence in Saddlebreds (5%). Prior research on them quantified the trait using a Measurement of Back Contour (MBC), defining an MBC of >7.0 centimeters as swayback, and8.0) MBC …

Biomarker Identification For Breast Cancer Types Using Feature Selection And Explainable Ai Methods, David E. La Rosa Giraud

Honors Undergraduate Theses

This paper investigates the impact the LASSO, mRMR, SHAP, and Reinforcement Feature Selection techniques on random forest models for the breast cancer subtypes markers ER, HER2, PR, and TN as well as identifying a small subset of biomarkers that could potentially cause the disease and explain them using explainable AI techniques. This is important because in areas such as healthcare understanding why the model makes a specific decision is important it is a diagnostic of an individual which requires reliable AI. Another contribution is using feature selection methods to identify a small subset of biomarkers capable of predicting if a …

Enhancing Tomato Fruit Quality: Application Of Crispr/Dcas9-Mediated Methylation On The Pg Gene Promoter Region, Irena Komninakas

Holster Scholar Projects

Commercially produced tomatoes are typically harvested well before maturation in order to withstand domestic and international distribution. While this process ensures unspoiled goods, the nutritional value of the fruits have been curtailed as a result of premature harvesting. Previous research has found that the polygalacturonase gene (PG gene) is responsible for cell wall degradation of the tomato. In this study, CRISPR/dCas9 technology was employed to increase methylation levels in the promoter regions of the PG gene. This method is significant in that it epigenetically modifies the tomato genome using a technique that has the potential to develop non-genetically modified progeny …

Statistical Methods For Gwas And The Impact Of Diabetic Medication Adherence On Healthcare Costs, Meida Wang

Dissertations, Master's Theses and Master's Reports

This dissertation includes three Chapters. In Chapter One, we develop a computationally efficient clustering linear combination approach to jointly analyze multiple phenotypes for GWAS. In this paper, based on the existing CLC method and ACAT strategy, we develop the ceCLC method to test association between multiple phenotypes and a genetic variant. In Chapter Two, we develop a novel method called sCLC for association studies of multiple phenotypes and a genetic variant based on GWAS summary statistics. Simulation results show that sCLC can control Type I error rates well and has the highest power in most scenarios. In Chapter Three, we …

Sequencing Antisense Transcriptome Of Populus Through Antisense/Sense Transcript Pair Enrichment, Emma V. Burke

Dissertations, Master's Theses and Master's Reports

Past transcriptome research on plants focused primarily on protein coding genes, and only recently researchers began looking into the non-protein coding regions that may play significant roles in gene regulation. Antisense RNA transcripts that are found naturally in the cell share complementary sequence with sense transcripts and have been shown to regulate expression of their sense counterparts. Since antisense RNA has been largely under-studied and difficult to sequence because of their low relative abundance, new methods are needed to target antisense RNA for efficient genome-wide profiling. To address this gap in methods to efficiently and cost effectively enrich antisense RNA …

White-Tailed Deer In A Winter-Wonderland: Long-Term Deer Yard Use And Methodological Considerations For Ungulate Fecal Dna Metabarcoding, Melanie A. Ottino

Dissertations, Master's Theses and Master's Reports

Northern white-tailed deer (Odocoileus virginianus) mitigate the increased energetic costs of severe winter conditions through obligate migration to densely congregated areas with abundant conifer cover, a behavior referred to as yarding. “Deer yards” in the Western Upper Peninsula (UP) of Michigan are principally located within the reduced snowpack and increased ambient temperature microclimates of densely canopied eastern hemlock (Tsuga canadensis) stands, but specific drivers of long-term site fidelity and utilization are largely uncharacterized. As an important game species of high economic and cultural value and a keystone herbivore with critical impact of plant community composition and structure, identifying winter yarding …

Statistical Methods For Gene Selection And Genetic Association Studies, Xuewei Cao

Dissertations, Master's Theses and Master's Reports

This dissertation includes five Chapters. A brief description of each chapter is organized as follows.

In Chapter One, we propose a signed bipartite genotype and phenotype network (GPN) by linking phenotypes and genotypes based on the statistical associations. It provides a new insight to investigate the genetic architecture among multiple correlated phenotypes and explore where phenotypes might be related at a higher level of cellular and organismal organization. We show that multiple phenotypes association studies by considering the proposed network are improved by incorporating the genetic information into the phenotype clustering.

In Chapter Two, we first illustrate the proposed GPN …

Can Testing The Environment For Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2) Be A Signal For Coronavirus Disease 2019 (Covid-19) Cases Among Nursing Home Staff?, Gabrielle M. Gussin, Raveena D. Singh, Izabela Coimbra Ibraim, Raheeb Saavedra, Thomas T. Tjoa, Micaila Curtis, Kristine P. Nguyen, Ilhem Messaoudi, Susan S. Huang

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prior to widespread COVID-19 vaccination, nursing homes were required to perform comprehensive weekly testing of staff. After the vaccine became available, testing became symptom-based for vaccinated staff despite continued waves of different severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variants. Nursing homes need pragmatic, affordable strategies to identify SARS-CoV-2–positive staff because financial and job-related pressures drive reluctance to disclose mild symptoms. We sought to determine whether positive environmental samples for SARS-CoV-2 could serve as trigger for comprehensive staff testing in lieu of weekly testing of all staff.

Correlates Of Sars-Cov-2 Anti-Rbd Igg Antibody Titers Among Persons Experiencing Homelessness In Los Angeles, Adeline Nyamathi, Sanghyuk S. Shin, Brianna M. Doratt, Alexandria Jones-Patten, Benissa Salem, Lillian Gelberg, Darlene Lee, Dana Garfin, Kartik Yadav, Alicia H. Chang, Kathryn White, Nicholas Arce, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objectives: People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions.

Design: A case–control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables.

Sample: A convenience sample of 97 PEH in Skid Row, Los Angeles.

Measurements: A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions.

Results: We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 …

Maternal Obesity Blunts Antimicrobial Responses In Fetal Monocytes, Suhas Sureshchandra, Brianna M. Doratt, Norma Mendza, Oleg Varlamov, Monica Rincon, Nicole E. Marshall, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to respiratory syncytial virus (RSV) and E. coli were significantly …