Genetics and Genomics Commons^™

Mitochondrial Dysfunction Reactivates Α-Fetoprotein Expression That Drives Copper-Dependent Immunosuppression In Mitochondrial Disease Models, Kimberly A Jett, Zakery N Baker, Amzad Hossain, Aren Boulet, Paul A Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John Decoteau, Karen Mochoruk, George N Ioannou, Christopher Savard, Sai Yuan, Osama Hmh Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J Battersby, Vishal M Gohil, Scot C Leary

Faculty, Staff and Students Publications

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative …

Follistatin Regulates The Specification Of The Apical Cochlea Responsible For Low-Frequency Hearing In Mammals, Hei Yeun Koo, Min-A Kim, Hyehyun Min, Jae Yeon Hwang, Meenakshi Prajapati-Dinubila, Kwan Soo Kim, Martin M Matzuk, Juw Won Park, Angelika Doetzlhofer, Un-Kyung Kim, Jinwoong Bok

Faculty, Staff and Students Publications

The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in …

Effects Of High-Pressure Processing On Cooked Color And Eating Qualities Of Dark-Cutting Beef, Cole Reesman, Gary Sullivan, Mary-Grace C. Danao, Gretchen G. Mafi, Morgan Pfeiffer, Ranjith Ramanathan

Department of Animal Science: Faculty Publications

High meat pH leads to an undercooked or an abnormal pink appearance in fully-cooked product. High-pressure processing (HPP) promotes protein denaturation. The objective was to evaluate the effects of HPP on cooked steak color and sensory attributes of dark-cutting beef. USDA Choice (mean pH = 5.5) and dark-cutting (mean pH = 6.3) strip loin sections were vacuum packaged and treated with 0 (no HPP), 300, 450, and 600 MPa of pressure for 90 s using chilled water. Steaks were randomly assigned to measure external cooked color, Warner- Bratzler shear force, and trained sensory panel. Applying 300 MPa of pressure improved …

A Comparison Of Microsatellites And Single Nucleotide Polymorphisms For The Assessment Of Population Structure In The Amblyomma Maculatum Koch, 1844 Species Complex, Henrey A. Deese

Electronic Theses and Dissertations

The Gulf Coast tick, Amblyomma maculatum Koch, 1844 is widespread throughout North and Central America and is the primary vector for the emerging pathogen Rickettsia parkeri. In the U.S., the population in the Southwest (A. maculatum morphotype III) is morphologically different from the population east of the Rocky Mountains (A. maculatum morphotype II). This research tests the hypothesis that A. maculatum morphotype II and morphotype III represent distinct species through the analysis and comparison of 6 microsatellite loci and suite of 135,221 Single nucleotide polymorphisms (SNPs) generated from ddRADseq. Population genetic analysis of both microsatellites and SNPs …

A Computational Analysis Of Hybrid Genome Assembly Strategies, Joseph Walewski

Computer Science Honors Papers

The central dogma of molecular biology states that DNA is transcribed to RNA and then translated into proteins. Since DNA is the starting material for many of biology’s macromolecules, it has been referred to as “nature’s instruction book.” The sum of all DNA in a cell is referred to as the genome, and genome sequencing is how we interpret the DNA.

Due to limitations on currently available technology, it is not possible to retrieve the entire genome in one contiguous set of data. Therefore, genome sequencing is a computer science problem as sequencing “reads” must be stitched together to obtain …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

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 …

Polygenic Scores Ignore Development And Epigenetics, Dramatically Reducing Their Value, David S. Moore

Pitzer Faculty Publications and Research

Polygenic scores cannot elucidate the mechanisms that produce behavioral phenotypes (including “intelligence”). Therefore, they are unlikely to yield helpful interventions. Moreover, they are poor predictors of individuals’ developmental outcomes. Burt’s critique is well-supported by the details of molecular biology. Specifically, experiences affect epigenetic factors that influence phenotypes via how the genome functions, a fact that lends support to Burt’s conclusions.

Molecular And Systemic Epigenetic Inheritance: Integrating Development, Genetics, And Evolution, Robert Lickliter, David S. Moore

Pitzer Faculty Publications and Research

Currently, a central problem for theoretical biology is the integration of development with genetics and evolutionary theory. Through the late 20^th century, biologists held that animals resemble their ancestors strictly because of the transgenerational transmission of DNA. This view effectively wrote development out of evolutionary biology. However, many molecular and developmental biologists now understand that phenotypes—anatomical, physiological, and behavioral traits—are not determined by genes (i.e., DNA segments) alone; instead, they emerge epigenetically from developmental processes involving co-acting genetic factors, environmental factors, molecular epigenetic factors, and other non-genetic factors within organisms’ bodies. This insight forces a rethinking of biological inheritance. …

Analysis Of A Cathepsin Protease In Normal Development And Tumor Metastasis In Drosophila Melanogaster, Lindsey Fannin

Mahurin Honors College Capstone Experience/Thesis Projects

Cysteine cathepsins are an important class of fifteen proteases with involvement in normal development and tumor progression. To better understand their contribution to these processes, the cathepsin L protease in Drosophila melanogaster was studied. In part one of this project, the role of this cathepsin in the normal development of Drosophila wings was analyzed. The GAL4/UAS-system and RNAi were used to downregulate this cathepsin in various regions of the wing and progeny were inspected for phenotypic irregularities. An abnormal phenotype of curved wings was found and hypothesized to be a result of apoptosis. Further experimentation will be required to prove …

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 …

White Coat Color Of A Black Angus Calf Attributed To An Occurrence Of The Delr217 Variant Of Mitf, Jessica Lynn Petersen, Renae Sieck, David Steffen

Department of Animal Science: Faculty Publications

A white calf, with minimal pigmented markings, was born to two registered Black Angus parents. Given the possibility of an unknown recessive or de novo dominant mutation, whole-genome sequencing was conducted on the trio of individuals. A 3-bp in-frame deletion in MITF was identified; this mutation was unique to the calf but identical to the delR217 variant reported in both humans and murine models of Waardenburg syndrome type 2A and Tietz syndrome. Given the coat color phenotype and identity of the mutation, our data support that this calf represents the first instance of this recurring MITF mutation in cattle.

Identification And Influence Of Species-Informative 16s Ribosomal Rna Sequences And Evaluation Of Ocean Biofilms, Nikhil Bose

Electronic Theses and Dissertations, 2020-2023

16S ribosomal RNA (rRNA) gene sequences are commonly analyzed for taxonomic and phylogenetic purposes because they contain variable regions that help distinguish genera. However, intra-genus classification is difficult due to high sequence similarity among closely related species. The biological impact of nucleotide variants in 16S variable regions are often unknown and hence their sequence differences are weighted evenly during classification, which provides poor species identity confidence. In this dissertation, I determined that analysis of intra-genus 16S allelic variants can provide species information and that nucleotide changes in 16S rRNA variable regions can impact ribosome quality. In one study, I analyzed …

Enhancement Of Developmental Defects In The Boron-Deficient Maize Mutant Tassel-Less1 By Reduced Auxin Levels, Michaela S. Matthes, Norman B. Best, Janlo M. Robil, Paula Mcsteen

Biology Faculty Publications

Background

Plant responses to deficiencies of the micronutrient boron are diverse and go beyond the well-characterized function of boron in cell wall crosslinking. To explain these phenotypic discrepancies, hypotheses about interactions of boron with various phytohormones have been proposed, particularly auxin. While these hypotheses are intensely tested in the root meristem of the model species, Arabidopsis thaliana, studies in crop species and the shoot are limited.

Aims

To address potential boron–auxin interactions during the vegetative and reproductive development of the crop maize (Zea mays), we utilized the boron-deficient tassel-less1 (tls1) mutant and the auxin-deficient vanishing tassel2 (vt2) mutant. We investigated …

Nuclear Phylogeny And Insights Into Whole-Genome Duplications And Reproductive Development Of Solanaceae Plants, Jie Wang, Weibin Xu, Junwen Zhai, Yi Hu, Jing Guo, Caifei Zhang, Yiyong Zhao, Lin Zhang, Christopher T. Martine, Hong Ma, Chien-Hsun Huang

Faculty Journal Articles

Solanaceae, the nightshade family, have ∼2700 species, including the important crops potato and tomato, ornamentals, and medicinal plants. Several sequenced Solanaceae genomes show evidence for whole-genome duplication (WGD), providing an excellent opportunity to investigate WGD and its impacts. Here, we generated 93 transcriptomes/genomes and combined them with 87 public datasets, for a total of 180 Solanaceae species representing all four subfamilies and 14 of 15 tribes. Nearly 1700 nuclear genes from these transcriptomic/genomic datasets were used to reconstruct a highly resolved Solanaceae phylogenetic tree with six major clades. The Solanaceae tree supports four previously recognized subfamilies (Goetzeioideae, Cestroideae, Nicotianoideae, …

Selective Gsk3b Overexpression In Medial Prefrontal Cortex Camkiia Cells Produces Sex-Specific Changes In Ethanol Self-Administration, Anxiety-Like Behavior, And Working Memory, Sam Gottlieb, Zachary Tatom, Michael F. Miles

Graduate Research Posters

Background: Glycogen synthase kinase 3 beta (Gsk3b) is central in a gene network regulated by ethanol in mouse medial prefrontal cortex (mPFC). GSK3B abundance/activity modulations regulate ethanol consumption, suggesting GSK3B could be a target in treating alcohol use disorder. However, the critical cell type in this ethanol response is not yet known, nor have sex differences in GSK3B modulations been fully investigated. Here we report results of GSK3B overexpression selectively in CamKIIa⁺ mPFC cells on multiple behaviors.

Methods: Mice underwent stereotaxic injections to overexpress GSK3B in mPFC CamKIIa⁺ cells or control virus (n=4-6/sex/virus). We assayed working …

Intraspecific Hybrid Identification Of Black Walnuts Via Marker Assisted Selection, Makenna B. Thompson

Graduate Theses/Dissertations

The improvement of Eastern black walnut (Juglans nigra L.) cultivars could increase market expansion. Improved cultivars with superior qualities would increase profitability for both the seller and the buyer. Agronomically and economically important traits such as heavier nut weight, disease resistance, tree structure integrity, and yearly nut production can be efficiently improved by breeding black walnuts via marker-assisted selection. Microsatellite/simple sequence repeat markers were used in this research to determine potential intraspecific hybrids between ‘Football’ and ‘Sparrow’ cultivars. Intraspecific is defined as of the same genus and species. This quality makes it more difficult to identify hybrids because the parent …

Morphological And Genetic Analysis Of The Root System In Two American Grapevines (Vitis Species), Parinaz Mohtasebi

Graduate Theses/Dissertations

The North American grapes species Vitis rupestris Scheele and Vitis riparia Michx have been the pillars of rootstock breeding for many decades. Though a large body of viticultural knowledge has been accumulated on their impact on grafted scions, the genetic basis of their root system architecture (RSA) has received limited scientific attention. In this study, I generated and analyzed adventitious root systems from dormant cuttings of 22 V. riparia and 19 V. rupestris accessions, as well as 162 interspecific F1 hybrid progeny from a cross between V. rupestris (♀) and V. riparia (♂). I photographed the roots and then extracted …

Molecular Investigation Of Minor Genomic Populations And Biological Exposures In Human Health, Brandon Ned Johnson

Dissertations and Theses

The study of genetics has contributed to countless discoveries related to human health and disease. However, the complexities of human biology reside not only in the genome but also in the contributions from environmental exposures, as measured via the classical twin design. To understand the influence of biological exposures, I implemented study designs to explore both the health associations and propagation of foreign genetic material. Microchimerism has been studied for association with several clinical conditions, and I further investigated if male microchimerism could elucidate the etiology of Mayer-Rokitansky-Küster-Hauser syndrome. Prevalence of male microchimerism in women with no history of pregnancy …

Estimation Of Breeding Values Using Different Densities Of Snp To Inform Kinship In Broiler Chickens, Mayara Salvian, Gabriel Costa Monteiro Moreira, Ândrea Plotzki Reis, Brayan Dias Dauria, Fabrício Pilonetto, Izally Carvalho Gervásio, Mônica Corrêa Ledur, Luiz Lehmann Coutinho, Matthew L. Spangler, Gerson Barreto Mourao

Department of Animal Science: Faculty Publications

Background: Traditionally, breeding values are estimated based on phenotypic and pedigree information using the numerator relationship (A) matrix. With the availability of genomic information, genome-wide markers can be included in the estimation of breeding values through genomic kinship. However, the density of genomic information used can impact the cost of implementation. The aim of this study was to compare the rank, accuracy, and bias of estimated breeding values (EBV) for organs [heart (HRT), liver (LIV), gizzard (GIZ), lungs (LUN)] and carcass [breast (BRST), drumstick (DRM) and thigh (THG)] weight traits in a broiler population using pedigree-based BLUP (PBLUP) and …

Effect Of Increasing Corn Silage Inclusion In Finishing Diets Cattle With Or Without Tylosin On Performance And Liver Abscesses, Hannah C. Wilson, Levi J. Mcphillips, Bradley M. Boyd, Andrea K. Watson, Jim C. Macdonald, Galen E. Erickson

Department of Animal Science: Faculty Publications

A pooled analysis was performed to evaluate whether corn silage fed at 15% or 45% of diet DM impacted liver abscesses prevalence at slaughter in five previous experiments. Cattle fed 15% corn silage had 7.8% abscessed livers compared to 4.1% for cattle fed 45% corn silage when all diets contained tylosin. While improved due to increased corn silage inclusion, the objective of the current finishing study was to determine the impact of silage inclusion in finishing diets with and without tylosin on performance and incidence of abscessed livers in beef cattle. A total of 640 (BW = 334 ± 25 …

Prostaglandin F2Α Regulates Mitochondrial Dynamics And Mitophagy In The Bovine Corpus Luteum, Michele R. Plewes, Emilia Przygrodzka, Corrine F. Monaco, Alexandria P. Snider, Jessica A. Keane, Patrick D. Burns, Jennifer Wood, Andrea Cupp, John S. Davis

Department of Animal Science: Faculty Publications

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, …

Differential Diagnosis Of Dna Viruses Related To Reproductive Disorder On Sows By Multiplex-Pcr Technique, T N. Nguyen, H T T Le, H L X Vu, P X. Dinh

Department of Animal Science: Faculty Publications

The newly emerged diseases caused by ASFV and PCV3 and their confirmed prevelance in Vietnam whereas most of available common commercial methods such as ELISA or realtime PCR designed for detecting single pathogen per reaction, highlighted a necessity for another diagnostic method to simultaneously detect and differentiate DNA viruses that are related to reproductive failures in sow herds including PCV2, PCV3, PPV, ASFV. In this communication, a diagnostic multiplex-PCR (mPCR) was established with pathogen-specific primers selected from previous studies and another set of primers designed for COX1 gene serving as an internal amplification control (IAC). The predicted products of PCV2, …

Ovarian Inflammation Mediated By Toll-Like Receptor 4 Increased Transcripts Of Maternal Effect Genes And Decreased Embryo Development, Alison F. Ermisch, Katie L. Bidne, Scott G. Kurz, Kerri A. Bochantin, Jennifer R. Wood

Department of Animal Science: Faculty Publications

Obese women are subfertile and have reduced assisted reproduction success, which may be due to reduced oocyte competence. We hypothesize that consumption of a high-fat/high-sugar diet induces ovarian inflammation, which is a primary contributor to decreased oocyte quality and pre-implantation embryo development. To test this hypothesis, C57BL/6 (B6) mice with a normal inflammatory response and C3H/HeJ (C3H) mice with a dampened inflammatory response due to dysfunctional Toll-like receptor 4 were fed either normal chow or high-fat/high-sugar diet. In both B6 and C3H females, high-fat/high-sugar diet induced excessive adiposity and hyperglycemia compared to normal chow-fed counterparts. Conversely, ovarian CD68 levels and …

Evaluating Draft Environmental Protection Agency Emissions Models For Broiler Operations, G. Li, R. S. Gates, B. C. Ramirez, R. T. Burns

Department of Animal Science: Faculty Publications

In August 2021, the U.S. Environmental Protection Agency( EPA) released draft models to estimate daily NH3, H2S, PM2.5, PM10, and total suspended particulate semissions from U.S. broiler operations using inputs of daily mean ambient temperature, relative humidity, and live animal weight. The EPA developed these models using data sets collected between 2005 and 2007. It is important to note that over 15 yr have passed since the original data were collected, and broiler genetics, nutrition, and management have improved consideably. These models, if adopted, could have substantial impact on the U.S. broiler industry regarding air emission management and regulation. The …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood

Bioelectrics Publications

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and …

Testing Evolutionary Conservation Of Sex Determination In Lepidoptera Using Crispr/Cas9 Gene Editing, Sophia Schroeder

Honors Theses

The mechanism of sex determination in Lepidoptera is largely unexplored, and limited to knowledge of only a few genes. Adult Lepidoptera have obvious sexually dimorphic qualities, such as their genitalia. However, significant sex determination genes are not imperative for the adult developmental stage. Knockouts of some sex determination genes (doublesex isoforms) are shown to be lethal in the embryonic and larval stages of development in several animals. However, it is unclear whether this is due to their respective impact on sex determination and sexual dimorphism, or the existence of another function, such as pleiotropy, within a particular gene. Moreover, …

Extracting High-Molecular Weight Dna From Cyanobacteria Using Promega's Wizard® Hmw Dna Extraction Kit With A Modified Protocol, Metis, Megan A. Hept, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

Extraction of high molecular weight (HMW) DNA for long read sequencing with little to no fragmentation and high purity is difficult to acquire from cyanobacterial species. Here we describe a modified method of extraction using Promega's Wizard® HMW DNA Extraction Kit to acquire high molecular weight DNA from cyanobacterial species. The protocol used in the kit is the “3.D. Isolating HMW DNA from Gram-Positive and Gram-Negative Bacteria” protocol. During a key step in the protocol, the lingering remnants of the mucilage layer of the cyanobacterial species is removed, preventing it from sticking to the DNA pellet produced. This customized modification …

Association Of Interpersonal Trauma And Polygenic Risk Scores With Depressive Symptoms In College Students, Rowan K. O'Hara

Theses and Dissertations

Major depression is considered a complex trait influenced by both polygenic risk factors and environmental exposures, such as childhood trauma. This study applied statistical genetic methods to calculate aggregate genetic risk for major depression to predict depressive symptoms scores in a college student sample. Data were from the Spit for Science (S4S) study in which college students from a large urban university self-reported interpersonal trauma (IPT) exposure prior to college and depressive symptoms from the past month (N = 7502; ancestry group: 20% African [AFR], 12% Admixed Americas [AMR], 10% East Asian [EAS], 49% European [EUR], 8% South Asian [SAS]). …