Genetics and Genomics Commons^™

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

Go West: Population Genomics Reveals Unexpected Population Fluctuations And Little Gene Flow In Western Hemisphere Populations Of The Predatory Lady Beetle, Hippodamia Convergens, Arun Sethuraman, Schyler O. Nunziata, Angela Jones, John J. Obrycki, David W. Weisrock

Entomology Faculty Publications

Hippodamia convergens—the convergent lady beetle, has been used extensively in aug- mentative biological control of aphids, thrips, and whiteflies across its native range in North America, and was introduced into South America in the 1950s. Overwintering H. convergens populations from its native western range in the United States are com- mercially collected and released across its current range in the eastern USA, with little knowledge of the effectiveness of its augmentative biological control. Here we use a novel ddRADseq-based SNP/haplotype discovery approach to estimate its range- wide population diversity, differentiation, and recent evolutionary history. Our results indicate (1) significant population …

N(Alpha)-Acetyltransferase 40-Mediated Histone Acetylation Plays An Important Role In Ecdysone Regulation Of Metamorphosis In The Red Flour Beetle, Tribolium Castaneum, Sharath Chandra Gaddelapati, Smitha George, Anilkumar Moola, Karthi Sengodan, Subba Reddy Palli

Entomology Faculty Publications

Histone acetylation, a crucial epigenetic modification, is governed by histone acetyltransferases (HATs), that regulate many biological processes. Functions of HATs in insects are not well understood. We identified 27 HATs and determined their functions using RNA interference (RNAi) in the model insect, Tribolium castaneum. Among HATs studied, N-alpha-acetyltransferase 40 (NAA40) knockdown caused a severe phenotype of arrested larval development. The steroid hormone, ecdysone induced NAA40 expression through its receptor, EcR (ecdysone receptor). Interestingly, ecdysone-induced NAA40 regulates EcR expression. NAA40 acetylates histone H4 protein, associated with the promoters of ecdysone response genes: EcR, E74, E75, and HR3, and causes an increase …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …

Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Phosphodiesterase-6 (PDE6) serves as a pivotal component in the phototransduction pathways of both cone and rod photoreceptors. In cones, PDE6 consists of tetrameric subunits: inhibitory (γ') and catalytic (α'). The catalytic subunit, PDE6α', contains a C-terminal prenylation motif. Deletion of this motif is associated with achromatopsia (ACHM), a form of color blindness. The mechanisms underlying the disease and the roles of PDE6 lipidation in vision remain elusive. Meanwhile, rod PDE6 is composed of α and β catalytic subunits and γ inhibitory subunits, with alterations in the C-terminal "prenylation motif" of PDE6β linked to retinitis pigmentosa (RP) pathology. In this comprehensive …

Contemporary Vs. Traditional Dna-Based Mutation Testing To Detect Hereditary Breast And Ovarian Cancer Syndrome (Hboc) In Women: A Meta Narrative Review, Hannah Olivia Cantu, Jacob Hipp, Nyela Y. Lopez, Duc Duy Nguyen

Research Methods Poster Session 2024

No abstract provided.

The Genetic Diversity Of An Endangered Buttercup, Ranunculus Triternatus, Ryan Garcia

All Master's Theses

Ranunculus triternatus, a rare endemic species of the Columbia River Gorge, faces conservation challenges due to its limited range and fragmented populations. This study assesses the genetic diversity of R. triternatus and compares it with its widespread congener, Ranunculus glaberrimus, using inter-primer binding site (iPBS) markers. Genetic data from 80 individuals across eight populations were analyzed using Nei’s genetic diversity, Shannon’s diversity index, and AMOVA. Results showed R. triternatus had higher genetic diversity than western populations of R. glaberrimus, with eastern populations of R. glaberrimus displaying greater diversity than western ones. PCA, UPGMA, and STRUCTURE analysis revealed …

A Balancing Act: Microrna Mediated Insect-Bacterial Homeostasis And The Tsetse Fly, Mason Hubbard Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

Microbial symbioses are ubiquitous across all kingdoms of life with broad and diverse impacts on the evolution of species. The sum of all microbes living in, on, or otherwise in close association with a host form the microbiota. In some cases, the development of a stable microbial association seems to have been necessary for the specialization of diet, as can be observed in numerous insect species, especially wood-eating, sap-feeding, and blood-feeding organisms. For the medically and economically tsetse fly (family Glossinidae), the mutualistic bacteria Wigglesworthia glossinidia is required for proper reproduction and supplementation of nutrients that the fly does not …

The Function Of Protein Glutamylation In Vision, Rawaa Aljammal

Graduate Theses, Dissertations, and Problem Reports (ETD)

Posttranslational glutamylation of protein has emerged as a novel candidate for cellular integrity. In a dynamic process, Tubulin Tyrosine Ligase Like proteins (TTLLs) introduce glutamate groups to their substrates, while Cytosolic Carboxypeptidases members (CCP1-CCP6) remove these glutamate groups. The outcome of this interplay is a wide range of substrates; each is glutamylated to a level crucial for its function.

Protein glutamylation is particularly abundant in neurons and in the axoneme of cilia and flagella. This distribution, along with the correlation between imbalanced glutamylation levels and compromised cellular functions, underscores the significance of protein glutamylation in maintaining cellular viability. However, the …

Genetic Diversity Of Paxistima Canbyi A. Gray: Conserving A Rare Plant Species Endemic To The Eastern United States, Isaac Buabeng

Master’s Theses

Premise: The glacial cycles of the Pleistocene period likely had a profound impact on the genetic diversity and phylogeographic patterns of numerous plant taxa in North America. However, the genetic diversity of rare, limestone-endemic woody species has not been highlighted. This study assesses genetic diversity in Paxistima canbyi A. Gray (Canby’s mountain lover or rat stripper), a rare limestone endemic small woody plant.

Methods: We investigated the genetic diversity of P. canbyi using genomic Single Nucleotide Polymorphism (SNP) data from 165 individuals from 14 populations sampled from across the entire range distribution. We first; de novo assembled the SNP …

Robust Phylogenetic Regression, Richard Adams, Zoe Cain, Raquel Assis, Michael Degiorgio

Entomology and Plant Pathology Faculty Publications and Presentations

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has shown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution—the primary justification for using …

Harnessing Microrna-Enriched Extracellular Vesicles For Liquid Biopsy, Song Yi Ko, Wonjae Lee, Honami Naora

Faculty, Staff and Student Publications

Extracellular microRNAs (miRNAs) can be detected in body fluids and hold great potential as cancer biomarkers. Extracellular miRNAs are protected from degradation by binding various proteins and through their packaging into extracellular vesicles (EVs). There is evidence that the diagnostic performance of cancer-associated extracellular miRNAs can be improved by assaying EV-miRNA instead of total cell-free miRNA, but several challenges have hampered the advancement of EV-miRNA in liquid biopsy. Because almost all types of cells release EVs, cancer cell-derived EVs might constitute only a minor fraction of EVs in body fluids of cancer patients with low volume disease. Furthermore, a given …

The Influence Of Genes On The Migratory Timing Of Great Reed Warblers, Emily Fackler

Honors Undergraduate Theses

Many organisms migrate; however, there is a lack of knowledge on the mechanisms that drive migration timing, including which genes play a role. The great reed warbler (Acrocephalus arundinaceus), a migratory bird that breeds in Eurasia and overwinters in sub-Saharan Africa, is an excellent model to study the genetics of migration. Each season, some individuals migrate early, whereas others migrate later in the season. In other words, they exhibit differences in their migratory chronotypes. Past research has identified three candidate genes (TOP1, PEAK1, and CPNE4) that influence the migratory chronotypes of another avian species, …

Identification Of Constrained Sequence Elements Across 239 Primate Genomes, Lukas F K Kuderna, Jacob C Ulirsch, Sabrina Rashid, Mohamed Ameen, Laksshman Sundaram, Glenn Hickey, Anthony J Cox, Hong Gao, Arvind Kumar, Francois Aguet, Matthew J Christmas, Hiram Clawson, Maximilian Haeussler, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rouselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Ioannis Karakikes, Kevin C Wang, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Adam Siepel, Anshul Kundaje, Benedict Paten, Kerstin Lindblad-Toh, Jeffrey Rogers, Tomas Marques Bonet, Kyle Kai-How Farh

Faculty, Staff and Students Publications

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of …

Editing The Tri5 Gene Of Fusarium Graminearum Using Crispr/Cas9, Madelyn Rae Waters

Honors Program Theses

No abstract provided.

The Genetic Basis Of Two Reproductive Traits In Monkeyflowers: Stigma Closure And Corolla Carotenoids, Rachel Anne Halperin

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Abstract

The interactions between pollinators and flowers have long been a driving force for the evolution of many physical floral traits. Traits such as flower shape, size, color, and smell are just some of these traits that evolve because of these interactions. This evolution does not only occur in the more obvious morphological floral traits, however, but also in more subtle traits like touch sensitive stigma closure. In hundreds of Lamiales species, the bilobed stigma, the organ that receives pollen from pollinators, closes rapidly upon touch. Theory and experiments show that this novel dynamic reproductive trait increases pollen export and …

Re-Programming Transcription Factor Function For Neuroscience Research Of Addiction: Investigating The Role Of Zinc Finger Proteins In Driving Cocaine Reinforcement In Mice, Joseph A. Picone

Theses and Dissertations

Administration of addictive drugs like cocaine or morphine initiates aberrant gene transcription within brain reward circuitry neurons, which contributes to the lasting behavioral maladaptations that define addiction. The drug-induced expression and function of key brain transcription factors (TFs) is one major mechanism through which these drugs are able to regulate transcription, and as a consequence, lasting damaging drug-related behaviors including compulsive drug use. The goal of this dissertation is to more fully understand the molecular mechanistic drug-specific actions of TFs within the rodent nucleus accumbens (NAc). The findings from these studies could serve as the basis to identify novel candidate …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …