Genetics and Genomics Commons^™

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 …

Using Genetically Heterogenous Mice To Identify Regulators Of Immune Checkpoint Blockade Response, Justin Hackett

Wayne State University Dissertations

Immune Checkpoint Inhibitors (ICI) have dramatically improved patient outcomes in metastatic lung cancer, metastatic melanoma, subtypes of renal cancer and others. However, despite the clinical success, most patients still fail to have a durable response. Understanding what determines response and predicting who will respond to therapy is essential to improving patient outcomes. To investigate genetic underpinnings of ICI response we utilized F1 crosses of C57Bl/6 with Diversity Outbred mice (DOB6F1) and multiple Collaborative Cross (CC) strains to identify and validate (respectively) genetic loci that associated with response to ICI. The genomic data suggested that the lactation and immunomodulatory peptide prolactin …

Functional Analysis Provides Insight Into Missing Heritability, Scott L. Baughan, Michael A. Tainsky, Fatima Darwiche

Medical Student Research Symposium

Accurate ascertainment of genetic risk can be potentially lifesaving for patients who inherit cancer promoting mutations. However, even with the most extensive panel testing clinically available, a large number of patients will test negative despite family history of cancer or test positive for a variant of unknown significance (VUS). For these patients, clinical management is complicated; patients want to know their risk, and may fear disease they are not at great risk for (benign VUS) or they may not be given access to potentially lifesaving early screening procedures (pathogenic VUS). ATM has proven a challenge to clinicians due to its …

Very Long Chain Acyl-Coa Dehydrogenase Deficiency Diagnosed By Michigan Newborn Screening And Their Cardiac Complications, Lindsay Jenkins, Kara Pappas Md, Shagun Kaur Md, Marissa Younan Ms, Cgc

Medical Student Research Symposium

With the expansion of newborn screening (NBS), there has been an increase in the number of patients diagnosed with genetic and metabolic conditions before the onset of symptoms. Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD) is a genetic disorder of fatty acid metabolism that can cause hypoglycemia, myopathy, rhabdomyolysis, cardiomyopathy and cardiac arrhythmias. VLCADD was included in the Michigan NBS in 2005 and since then, our center has diagnosed 28 patients with VLCADD. We have observed that many of these patients are asymptomatic or have a mild disease presentation. These patients may also have a lower incidence of cardiac complications than …

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

The Biodiversity Of Freshwater Crustaceans Revealed By Taxonomy And Mitochondrial Dna Barcodes, Adrian Amelio Vasquez, Brittany L. Bonnici, Donna R. Kashian, Jorge Trejo-Martinez, Carol J. Miller, Jeffrey L. Ram

Physiology Faculty Research Publications

Cytochrome oxidase subunit I (COI) barcode sequences in this file were obtained from specimens collected by plankton net in western Lake Erie in 2012 & 2013, along with later specimens collected at various locations and times, including some collected in Belize in 2015. Methods and other details about these sequences are described in a paper by the same authors in a submitted publication (2021: URL to be given here when published). The right columns below contain additional notes on lengths of sequences, GenBank accession ID (when obtained), and annotation as to whether the sequence represents a new barcode for its …

A Multispecies Perspective Into Dietary Genetic Adaptations And Ancient Migration In The Peruvian Andes, Kelsey Jorgensen

Wayne State University Dissertations

Successful adaptation to the high-elevation Andes would have required both cultural and biological adaptations by early human populations. These past adaptations continue to shape the evolutionary outcomes of both humans and non-human species today. A multispecies perspective was used to examine how humans and non-human creatures, specifically insects, were shaped by past human adaptations. This dissertation asked two primary questions: 1) Given the importance and evolutionary history of potato consumption in the Peruvian Andes, is a genetic adaptation to better digest potato starch detectable in present-day Peruvians? and 2) Using the Andean Potato Weevil (APW) phylogeny as a proxy, what …

Functional Characterization Of Threonine 49 Phosphorylation Of Cytochrome C, Antoine Khobeir

Wayne State University Theses

Cytochrome c (Cytc) is a pivotal multifunctional mitochondrial protein that serves as a single electron carrier between complexes III and IV of the electron transport chain. It has important roles in both cellular respiration and apoptosis. The novel Thr49 (T49) phosphorylation of Cytc likely affects mitochondrial respiration, membrane potential, ROS production, ATP production, and apoptosis. Based on the functional characterization of previously mapped phosphorylation sites (Tyr97, Tyr48, Thr28, Ser47, Thr58) of the lab, we hypothesize that T49 phosphorylation will lead to controlled respiration, optimal intermediate mitochondrial membrane potential, lower ROS production, and inhibition of apoptosis compared to unphosphorylated Cytc. Here …

Novel Role Of Endoplasmic Reticulum-Associated Degradation In The Regulation Of Ceruloplasmin, Stephen William Hippleheuser

Wayne State University Theses

Ceruloplasmin (Cp) is a secreted ferroxidase produced by the hepatocytes that assists in the transport of iron throughout the human body. In human aceruloplasminemia patients, due to Cp deficiency excess intracellular iron buildup leads to ailments like liver cirrhosis, neurodegeneration, and blindness. We recently found that the biogenesis of Cp in the endoplasmic reticulum (ER) is regulated by a principal ER quality-control process, ER-associated degradation (ERAD). ERAD clears misfolded ER proteins for cytosolic proteasomal degradation, with the Sel-1 suppressor of lin-12-like (Sel1L)-HMG-CoA reductase degradation 1 (Hrd1) protein complex representing the most conserved branch in mammals. Interestingly, we found that Sel1L-Hrd1 …

Mite Diet Sequences Obtained By High Throughput Sequencing Of Gut Contents Of Freshly Collected Water Mites, Adrian Amelio Vasquez, Obadeh Mohiddin, Zeyu Li, Brittany L. Bonnici, Katherine Gurdziel, Jeffrey L. Ram

Physiology Faculty Research Publications

Cytochrome oxidase subunit I (COI) barcode sequences in this file were obtained from gut DNA extracted from 54 freshly collected water mites, comprising 21 Lebertia quinquemaculosa , 30 Lebertia davidcooki , 1 Limnesia , and 2 Arrenurus specimens. Methods and other details about these sequences are described in a paper by the same authors in a submitted publication (2021: URL to be given here when published). Data on collection locations, primers (mLep and LCOI), amino acid translations, etc. are included in corresponding sequences uploaded to GenBank. The right column below contains additional notes on naming the taxa of the sequences …

Mnrr1: Understanding The Role Of A Novel Mitochondrial-Nuclear Regulator, Stephanie L. Gladyck

Wayne State University Dissertations

Mitochondria are complex organelles that generate most of the energy required to sustain life and function in metabolic and signaling pathways required to maintain cellular homeostasis. MNRR1 (mitochondrial nuclear retrograde regulator 1 or CHCHD2) is a small, bi-organellar twin CX9C protein that is emerging as an important regulator of mitochondrial function, apoptosis, and cellular stress by participating in mitochondrial-nuclear crosstalk. Our lab has previously shown that in the mitochondria, MNRR1 regulates complex IV (Cytochrome c oxidase or COX) and is able to finetune the oxidase function through phosphorylation status. We have also shown that during stress, mitochondrial MNRR1 levels deplete, …

Modulation Of Pharyngeal Health In Bacterial Diet-Dependent Survival, Deniz Sifoglu

Wayne State University Dissertations

ABSTRACT

MODULATION OF PHARYNGEAL HEALTH IN BACTERIAL DIET-DEPENDENT SURVIVAL

by

DENIZ SIFOGLU

August 2021

Advisor: Dr. Joy Alcedo Major: Biological Sciences Degree: Doctor of Philosophy Both diet and bacterial microbiome modulate insulin signaling, which regulates key physiological processes that are important for survival. However, the mechanisms through which diet and the microbiome modulate insulin signaling remain unclear. To understand these mechanisms, I turned to the nematode worm C. elegans, whose diet consists of different types of bacteria. Like humans and other animals, C. elegans has to modulate its responses to its diet and to bacteria to optimize its survival. Because …

Mitochondrial Dna Diversity And Evolutionary History Of Native Human Populations Of Northwest Patagonia (Argentina), María Bárbara Postillone, Virginia Agustina Cobos, Celmira Urrutia, Cristina Beatriz Dejean, Paula N. Gonzalez, Sergio Ivan Perez, Valeria Bernal

Human Biology Open Access Pre-Prints

The genetic composition of Amerindian descendants from Patagonia has long been a focus of interest, although the information available is still scarce for many geographic areas. Here, we report the first analysis of the variation in the mtDNA control region for an area of northwestern Patagonia, the North of Neuquén, with the aim of studying the processes and historical events that modeled the evolutionary history of these human groups. We analyzed 113 individuals from two localities of northern Neuquén, along with 6 from southern Neuquén and 223 mtDNA sequences previously published from neighboring areas from Argentina and Chile. We estimated …

Addressing The Issue Of Missing Heritability: The Importance Of Apoptosis In Hereditary Breast And Ovarian Cancer And Functional Assessment Of Tp53i3-S252*, Sophia Chaudhry

Wayne State University Dissertations

A quarter of all cases of ovarian cancer (OVCA) cases are due to inherited factors. However, much of the genetic risk remains unknown. We have previously established the importance of whole exome sequencing to answer the question for missing heritability. We identified clinically actionable and novel risk loci in the DNA repair and cell cycle regulation pathways by assessing a cohort of women diagnosed with OVCA, wildtype for BRCA1/BRCA2 and suspected to be hereditary due to family history of breast cancer/OVCA. Equally as important was the exploration and discovery of novel risk loci in the apoptosis pathway. A total of …

A Mechanism For Sex Determination In Dioecious Cultivated Spinach, Nicholas West

Wayne State University Dissertations

While unisexual flowers have evolved repeatedly throughout angiosperm families, the actual identity of sex determining genes has been elusive, and their regulation within populations remains largely undefined. Additionally, sex liability is often observed in unisexual plants and has been correlated to external and internal cues, suggesting that the genes responsible for unisexual morphology are not necessarily segregating but rather differentially regulated. Understanding these processes will be of significant theoretical and agronomical importance.

Cultivated spinach is a dioecious species in which an individual will bear alternative sexual organs. Previous work has identified spinach B class floral organ identity genes, SpAP3 and …

How The Atacama Skeleton Might Advance Discussion Of Responsible Conduct Of Research Responsibilities, Thomas May, Mariko Nakano-Okuno

Human Biology Open Access Pre-Prints

Controversies resulting from genetic testing on skeletal remains of disputed stewardship raise important questions about obligations inherent on genetic researchers to assure ethical chain of custody. In this paper, we analyze and evaluate several proposed positions on whether such research should be published. Following jurisprudential standards for legitimate regulatory systems, we argue that responsible conduct of research requires reasonable attention to chain of custody, but cannot require guarantees, particularly in cases of ancient remains.

Genetic Overview Of The Maya Populations: Mitochondrial Dna Haplogroups, Angélica González-Oliver, Dircé Pineda-Vázquez, Ernesto Garfias-Morales, Isabel De La Cruz-Laina, Luis Medrano-González, Lourdes Márquez-Morfín, Allan Ortega-Muñoz

Human Biology Open Access Pre-Prints

We identified the mitochondrial DNA haplogroups A, B, C and D in 75 present-day Maya individuals, 24 Maya individuals of the colonial period and one pre-Columbian Maya individual from Quintana Roo, Mexico. We examined these data together with those of 21 Maya populations accounting for 647 present-day Maya individuals and 104 ancient Maya individuals. A demographic study based on the analysis of fertility and endogamy was carried out in two modern Maya populations to identify cultural factors that influence the mitochondrial haplogroup genetic diversity. Most present-day and ancient Maya populations show a distribution pattern of mitochondrial haplogroup frequencies A, C, …

Genetic Variants Of Duffy And Hemoglobin S Genes In An Afrodescendent Population From Columbia, Diana C. Ortega, Heiber Cardenas, Guillermo Barreto

Human Biology Open Access Pre-Prints

Malaria is an endemic disease in a large part of Colombia, and the city of Buenaventura reports one of the highest malaria infection rates. Some genetic variants confer resistance to malaria, such as the heterozygote for hemoglobin S (HbS) and the homozygous variant FYB^ES/FYB^ES of the Duffy gene. The aim of this work was the molecular characterization of these genes in an afrodescendent population from the urban area of Buenaventura. A total of 819 individuals from a stratified random sampling in each of the 12 communities of this city were analysed. Molecular analysis was performed using PCR-RFLP, …

Complexity, Genetic Causation, And Hereditarianism, Charles Roseman

Human Biology Open Access Pre-Prints

Hereditarians have claimed that recent advances in psychological and psychiatric genetics support their contention that individual and group socially important aspects of behavior and cognition are largely insensitive to environmental context. This has been countered by anti- hereditarians who (correctly) claim that the conclusion of genetic ineluctability is false. Anti- hereditarians, however, sometimes use problematic arguments based on complexity and the ignorance that comes with complexity and a demand for mechanistic, as opposed to variational, explanations for the ways in which genes affect phenotype. I argue here, as a committed anti-hereditarian, that the complexity gambit and the demand for mechanisms …

Ontogenesis Of The Sella Turcica Among Egyptians: Forensic And Radiological Study, Wafaa Mohamed El-Sehly, Fatma Mohamed Magdy Badr El Dine, Mohamed Samir Shaban

Human Biology Open Access Pre-Prints

Introduction: The sella turcica has gained importance as a stable bony landmark in cephalometric studies.
Aim of the work: The aim of the work was to explore the changes that accompany postnatal ontogeny of the sella turcica until full development, and to verify its contribution in age estimation and sexual assignment among Egyptians.
Subjects and methods: Six selected measurements of the sella turcica of 215 Egyptian patients were assessed using Multidetector Computed Tomography (MDCT). The patients represented different ages and were referred to the Radiodiagnosis and Intervention Department. The gathered data were then subjected to statistical analysis including correlation and …

Probability, Populations, Phylogenetics And Hominin Speciation, Niccolo Caldararo

Human Biology Open Access Pre-Prints

A number of recent articles have appeared on the hominin Denisova fossil remains. Many of them focus on attempts to produce DNA sequences from the extracted samples. Often these project mtDNA sequences from the fossil remains of a number of Neandertal fossils and the Denisovans in an attempt to understand the evolution of Mid Pleistocene human ancestors. These papers, introduce a number of problems in the interpretation of speciation in hominins. One concerns the degradation of the ancient DNA and its interpretation as authentic genetic information. Another concerns the idea of “species” versus that of “population” and the use of …

The Development And Use Of Computational Tools In Forensic Science, Dennis E. Slice

Human Biology Open Access Pre-Prints

Modern computational resources make available a rich toolkit of statistical methods that can be applied to forensic questions. This toolkit is built on the foundation of statistical developments dating back to the 19th century. To fully and effectively exploit these developments, both the makers and users of software must be keenly aware of the quality, i.e., the accuracy and precision, of the data being modeled or analyzed, and end-users must be sufficiently familiar with the underlying theory to understand the process and results of any analysis or software they use. This is especially important for medico-legal personnel who might be …

Oxygen And Hydrogen Isotopes In Human Hair And Tap Water: Modeling Relationships In A Modern Mexican Population, Chelsey A. Juarez, Robin Ramey, David T. Flaherty, Belinda Akpa

Human Biology Open Access Pre-Prints

This study investigates the relationship between O and H isotopes in samples of Mexican hair and drinking water. The purpose of this study was twofold. First, we wanted to quantify the relationship between isotopes in Mexican hair and tap water to understand the impact of water stress and differing socioeconomic status on accurate predictions of drinking water. Second, we wanted to determine whether currently existing semi mechanistic models could accurately represent the relationship between hair and tap water. For this study, we used a subset of paired (N = 62) human hair and (N = 76) tap water samples. Isotope …

Age-At-Death Estimation For Modern Populations In Mexico And Puerto Rico Through The Use Of 3d Laser Scans Of The Pubic Symphysis, Cristina Figueroa Soto, Bridget F.B. Algee-Hewitt, Guillermo Bravo Morante, Dennis E. Slice, Dawnie W. Steadman

Human Biology Open Access Pre-Prints

Reliable age-at-death estimates from the adult skeleton is of fundamental importance in forensic anthropology, as it contributes to the identity parameters used in a medico-legal death investigation. However, reliable estimates are made difficult by the fact that many traditional aging methods are dependent upon a set of population-specific criteria derived from individuals of European and African descent. The absence of information on the potential differences in the aging patterns of underrepresented, especially Hispanic populations, may hinder our efforts to produce useful age-at-death estimates. In response to these concerns, this study explores the utility of currently available aging techniques, and explores …

Population Identifiability From Forensic Genetic Markers: Ancestry Variation In Latin America, Cris E. Hughes, Bridget F.B. Algee-Hewitt, Lyle Konigsberg

Human Biology Open Access Pre-Prints

The Combined DNA Index System (CODIS) loci are a standard microsatellite marker set widely used for distinguishing among individuals in forensic DNA identity testing for medico-legal casework in the United States and in other countries. In anthropological genetic research, CODIS markers have become an important tool for uses extending beyond case investigations to quantify ancestry proportions, reveals patterns of admixture and trace population histories. These investigations are especially prevalent in studies of Latin American population structure. Nevertheless, the accuracy of the ancestry estimates computed from the CODIS loci for highly admixed Latino populations has not been formally tested. Long-standing arguments …

Neanderthal And Woolly Mammoth Molecular Resemblance: Genetic Similarities Might Underlie Cold Adaptation Suite, Meidad Kislev, Ran Barkai

Human Biology Open Access Pre-Prints

With the ongoing growth of gene-based research in recent decades, the possibility of examining changes that have taken place in structures over the course of evolution has become increasingly accessible. One intriguing subject at the forefront of evolutionary research is that of how environmental pressures affect species evolution through epigenetic adaptation. In this paper we present the available molecular components of adaptation to cold environments in two extinct mammals – the woolly mammoth and the Neanderthal. These two species co-existed in similar geographic and environmental European settings during the Middle and Upper Pleistocene and both were direct descendants of African …

New Approaches To Juvenile Age Estimation In Forensics: Application Of Transition Analysis Via The Shackelford Et Al. Method To A Diverse Modern Subadult Sample, Kelly R. Kamnikar, Nicholas P. Herrmann, Amber M. Plemons

Human Biology Open Access Pre-Prints

Dental development is one of the most widely utilized and accurate methods available for estimating age in subadult skeletal remains. The timing of tooth growth and development is regulated by genetics and less affected by external factors, allowing reliable estimates of chronological age. Traditional methodology focuses on comparing tooth developmental scores to corresponding age charts. Using the Moorrees, Fanning, and Hunt (MFH) developmental scores, Shackelford and colleagues embed the dental development method in a statistical framework based on transition analysis. They generated numerical parameters underlining each “stage” and age-at-death distribution and applied them to fossil hominins and Neanderthals with limited …

Thinking Computationally About Forensics: Anthropological Perspectives On Advancements In Technologies, Data, And Algorithms, Bridget F.B. Algee-Hewitt, Jieun Kim, Cris E. Hughes

Human Biology Open Access Pre-Prints

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Who Needs Data? I’Ve Got Experience!, Dawnie Wolfe Steadman

Human Biology Open Access Pre-Prints

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