Medical Specialties Commons^™

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …

Comparative Effect Of Zoledronic Acid, High Glucose Levels, And Oxidative Stress On Macrophage Viability, Bryan Liu, Denae Cantu, Deborah Seixas, Cláudia Cristina Biguetti

School of Podiatric Medicine - Student Research

Introduction and Hypothesis: Zoledronate (Zol) is an antiosteoclastic drug widely utilized for osteoporosis and bone metastases, and it may be used off-label for managing diabetic Charcot neuroarthropathy¹. Since macrophages share common precursors with osteoclasts, their function may also be affected by Zol. Herein, we hypothesize that Zol impairs macrophage responses, potentially hindering their viability and host defense in diabetic conditions.

Methodology: Raw 264.7 macrophages were seeded at 2.5 x 10³ in 96-well plates for viability assays. Cells were tested under normal glucose (25 mM), high glucose (ranging from 45 to 70 mM), and high oxidative stress (ranging …

Energy Expenditure In Partial-Foot Amputees With Diabetes: A Scoping Review, Nicholas Obias, Madeleine G. Mehaffey, Amanda Killeen

School of Podiatric Medicine - Student Research

Objective: The energy cost of walking in amputees is often cited in modern scientific literature and clinical rationales for determining amputation levels. However, many referenced papers do not study diabetic populations with partial foot amputations (PFAs) – relatively widespread conditions in podiatric patient populations. Commonly cited papers include Waters (1976), which is significantly dated, Goktepe (2010), which studies traumatic PFAs in a military academy, and Jeans (2011), which studies traumatic PFAs in pediatric populations. These papers do not study diabetic populations and PFAs specifically. We hoped to find a study population more reflective of diabetic patients with PFAs.

Methods: …

Do We Need Another Frame? A Scoping Review On External Fixator Reuse, Nicholas Obias, James Hughes, Dustin Prins, Amanda Killeen

School of Podiatric Medicine - Student Research

Statement of Purpose: External fixators in the United States are sold as single-use devices. Though their efficacy is well documented, they remain underutilized due to expense. The aim of this study is to determine if it is safe to reprocess and reuse external fixator components to lower the cost burden of surgeries using external fixation.

Introduction: External fixation is a critical but costly modality for upper and lower limb pathologies, such as trauma, deformity correction, and nonunion. Despite the clinical effectiveness of external fixation using delta, ilizarov, and hexapod frames, its application in the United States as a single-use device …

Amniotic Graft Applications On A Healthy Elderly Patient With Neglected Chronic Wound Due To Trauma, Maya D. Kaafarani, Brittney White, Amanda L. Killeen

School of Podiatric Medicine - Student Research

Introduction: AM grafts are angiogenic, anti-inflammatory, anti-fibrotic, anti-microbial, non-immunogenic, and decrease the total time for complex, chronic wounds to heal. This poster will explore a single case study using an AM graft on an elderly male with a chronic wound and provide a brief overview of the general application of AM in chronic wounds.

Case Report: A healthy 92-year-old male sustained a traumatic wound to the dorsum of his foot after dropping a heavy welding torch. The wound was chronically neglected and progressed to tendons before he was taken in for evaluation and treatment. Through a series of amniotic …

Antagomir Treatment For Deep-Space Simulated Changes In The Liver Of Mice, Natalie P. Hayslip

Honors Undergraduate Theses

With the start of NASA’s Artemis program, astronauts will soon leave the protection of Earth’s magnetosphere. Previous studies have established a theme of liver dysregulation associated with the harmful radiation and microgravity experienced in deep space. MicroRNAs (miRNAs) are key regulators of many of the pathologies observed during and after spaceflight, including hepatic fibrosis, making them strong potential biomarkers and therapeutic targets. Therefore, in the present study we investigated the effects of simulated microgravity, galactic cosmic radiation (GCR), and solar particle events (SPE) on miRNAs and mRNAs involved in the TGF-β signaling pathway, a key regulator of fibrosis, senescence, and …

Assessing Preventive Care Utilization For Cardiovascular Disease Among U.S. Latinos, Melanie Helena Paredes

Honors Undergraduate Theses

Accounting for nearly 19% of the United States population in 2020, Latinos and Hispanics represent the second largest racial/ethnic group in the United States, totaling roughly 62.1 million people. Given the growing population size and longer life expectancy estimates amongst the U.S. Latino/Hispanic community, healthcare practitioners and public health officials are increasingly emphasizing the healthcare needs and outcomes of this population. Alarmingly, current literature has highlighted significant disparities in cardiovascular disease (CVD) incidence and risk factors among U.S. Latinos/Hispanics. As CVD continues to be one of the leading causes of death amongst all racial/ethnic groups across the United States, risk …

Understanding Guardian Perceptions Of Whole-Foods Plant-Based Diets As Interventions In Pediatric Medicine, Vijay R. Luthra

Honors Undergraduate Theses

The obesity epidemic is widespread in American society, often affecting children who bear its consequences innocently. Due to a lack of nutrition knowledge, children rely on caregivers to meet their nutritional needs and instill healthy habits. This study examines parents' attitudes, knowledge, and behaviors, as well as perceived barriers to adopting a whole-foods plant-based diet (WFPD) for their children. Using a modified survey instrument by Morton et al., this study focused on parents and children regarding dietary choices. Participants were recruited from the waiting area of a pediatric clinic at the Medical College of Georgia between April and May 2023. …

The Impact Of Gestational Diabetes Mellitus And Maternal Oral Microbiome: A Scoping Review, Jaclyn P. Langan

Honors Undergraduate Theses

Background: Gestational diabetes mellitus (GDM) is a common pregnancy-related metabolic disorder associated with adverse maternal and fetal outcomes. Recent research has highlighted the potential role of the oral microbiome in the pathophysiology of various systemic conditions, including diabetes mellitus. However, the impact of GDM on the maternal oral microbiome remains relatively understudied. Understanding alterations in the oral microbiome during pregnancy complicated by GDM could provide valuable insights into the mechanistic links between systemic metabolic disorders and oral health.

Objective: The objective of this scoping review was to comprehensively examine the existing literature on the relationship between GDM and maternal oral …

Identifying Contributing Factors For Legal Placement Status In Involuntary Commitment And Voluntary Commitment In Child And Adolescent Psychiatry, Brianna R. Perry

Honors Undergraduate Theses

Background: Psychiatric hospitalization of children and adolescents can be carried out either voluntarily or involuntarily. The aim of this form of inpatient hospitalization is to provide treatment for those who cannot manage the symptoms of their mental illnesses on their own. However, psychiatric hospitalizations of children and adolescents are costly and could lead to outcomes such as worsened mental state in former patients and distrust of the system in caregivers. It is crucial to have a solid understanding of specific components that lead to the hospitalization.

Purpose: To identify potential trends in patient admission data through the analysis …

How Hormonal Contraceptives Influence Injury In Female Athletes: A Systematic Review, Ashley V. Malvita

Honors Undergraduate Theses

Research indicates that female athletes have a higher risk of musculoskeletal injuries. Hormone fluctuations throughout the different periods of the menstruation cycle impacts the risk of injuries for women. Contraceptive use, most used in the form of an oral contraceptive pill, directly effects hormones and menstrual cycle related symptoms, with evidence of ameliorating some symptoms. Oral contraceptive use is suggested to influence musculoskeletal injuries in female athletes. However, there is little research and data that explores the direct relationship between oral contraceptive use and the injury rates of female athletes. Within this systematic review, five articles investigating this relationship fulfilled …

Investigating The Association Of Demographic Factors On Methotrexate Delay-Clearance And Toxicity In Pediatric Oncology Patients: A Retrospective Chart Review, Belal Alabdul Razzak

Honors Undergraduate Theses

High-dose methotrexate (HD MTX) is critical for treating pediatric malignancies such as acute lymphoblastic leukemia and neuro-carcinoma. However, its significant toxicity due to drug accumulation poses substantial risks. This retrospective study assesses the impact of demographic factors on MTX toxicity and clearance in pediatric oncology patients. Patient records from Saint Mary Hospital were analyzed, focusing on two MTX administration protocols: a 24-hour infusion followed by alkaline hydration and a 4-hour infusion followed by alkaline hydration. We hypothesize that factors such as age, body surface area (BSA), and body mass index (BMI) are associated with MTX clearance and toxicity. The study …

Co-Occurrence Of Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder With Idiopathic Hypersomnia: Data From The Hypersomnia Foundation Registry, Sophie Sevan Mikkelsen

Honors Undergraduate Theses

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine …

Assessment Of Forensic And Clinical Criteria Of Orbital Blowout Fractures For Use In Bioarchaeological Analysis, Dylan E. Ornot

Honors Undergraduate Theses

Orbital blowout fractures are a particular facial fracture occurring within the inner eye orbits of the face caused by blunt force trauma to the eyeball or the lower orbital rim. This fracture is common in modern clinical contexts due to physical assaults, but examining this fracture in skeletal material can also provide insights into the patterns of interpersonal violence within the fields of bioarchaeology and forensic anthropology. Issues with analyzing this fracture in skeletal material arise due to the clinical assessment practices of blowout fractures, where medical practitioners are highly focused on the soft tissue presentations of the fracture in …

Dance Movement Therapy For Pediatric Oncology Patients And Its Effect On Cancer Therapy-Related Symptoms, Victoria M. Trautwein

Honors Undergraduate Theses

Background: Pediatric cancer patients are susceptible to emotional distress, depression, anxiety, and physical symptoms impacting their quality of life. Dance movement therapy is a non-pharmacological method that has been shown to improve feelings of depression, anxiety, emotional, somatic symptoms, and overall quality of life. While much of cancer research is dedicated to finding cures, it is also important to focus on identifying methods for improving the symptoms and quality of life for pediatric cancer patients.

Aim: The purpose of the literature review is to examine studies that show the effects of dance movement therapy on pediatric oncology patients’ cancer-treatment related …

Unraveling The Effects Of The Covid-19 Pandemic On Staphylococcus Aureus Carriage: A Comparative Research Of Pre- And Post-Pandemic Samples, Catherine G. Johnston

Honors Undergraduate Theses

The COVID-19 pandemic brought about significant changes in the epidemiology of Staphylococcus aureus carriage and disease. This study aims to assess these changes by leveraging respiratory samples collected from a longstanding cohort, comparing the genomic characteristics of S. aureus isolates from pre- and post-pandemic periods. We analyzed S. aureus genomes and phenotypically determined macrolide resistance to characterize population structure, antibiotic resistance, and virulence profiles. Changes in S. aureus carriage rates, macrolide resistance, disease occurrence, and population structure between samples collected pre- and post-pandemic were examined. By using respiratory samples, chart reviews, and risk factor questionnaires of 498 children from a …

Ai And Radiologist Assessments On The Prevalence Of Tmj Osteoarthritis Using Radiographic Images: A Comparative Study, Louloua Mourad, Nayer Abo El Saad, Yehia El Mahallawy

International Arab Journal of Dentistry

Objectives: This study aims to address the significant discomfort and functional impairment associated with temporomandibular joint osteoarthritis (TMJ OA), which negatively impacts the quality of life. It emphasizes the importance of prompt diagnosis and explores the potential of an Artificial Intelligence (AI) system to enhance TMJ OA diagnosis.

Methods: The prevalence of TMJ OA was evaluated using 3 diagnostic tools: the gold standard, the AI model, and an examiner. In total, 132 patients who performed 190 cone-beam computed tomography (CBCT) images were included.

Results: The prevalence of TMJ OA was 62.11% using the gold standard, 63.68% using …

Improving Nutritional Delivery To Pediatric Patients On Continuous Renal Replacement Therapy, Jennifer Ruiz-Boada, Sarah Brunner, Tara Benton, Vimal Chadha

Presentations

INTRODUCTION: Continuous renal replacement therapy (CRRT) is used in critically ill children with acute renal failure. CRRT can lead to malnutrition by removing essential proteins and micronutrients. Malnutrition is associated with worse outcomes, including increased length of stay and mortality. CRRT guidelines suggest the importance of early nutrition and ensuring high protein intake. After evaluating our CRRT patients, we found sub-optimal adherence to the guidelines. This Quality Improvement project aimed to increase the percentage of patients achieving 75% of their goal protein and caloric intake by day 5 of CRRT initiation by 15% by August 2023. METHODS: A multidisciplinary group …

Role Of Wave3 As An Actin Binding Protein In The Pathology Of Triple Negative Breast Cancer, Lamyae El Khalki, Khalid Sossey-Alaoui

Faculty Scholarship

Breast cancer, a prevalent global health concern, has sparked extensive research efforts, particularly focusing on triple negative breast cancer (TNBC), a subtype lacking estrogen receptor (ER), progesterone receptor, and epidermal growth factor receptor. TNBC's aggressive nature and resistance to hormone-based therapies heightens the risk of tumor progression and recurrence. Actin-binding proteins, specifically WAVE3 from the Wiskott–Aldrich syndrome protein (WASP) family, have emerged as major drivers in understanding TNBC biology. This review delves into the intricate molecular makeup of TNBC, shedding light on actin's fundamental role in cellular processes. Actin, a structural element in the cytoskeleton, regulates various cellular pathways essential …

The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Oncogenic mutations activate secretory programs that drive tumor progression and represent therapeutic targets. The clinical relevance of CASPs is underscored by their prevalence, their linkages to specific genetic and epigenetic contexts, the proven efficacy of secretory blockade in preclinical models, and the availability of assays to identify vulnerable patient populations.

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

Effect Of Mitochondrial Oxidative Stress On Regulatory T Cell Manufacturing For Clinical Application In Transplantation: Results From A Pilot Study, Roberto Gedaly, Gabriel Orozco, Lillie J. Lewis, Deepa Valvi, Fanny Chapelin, Aman Khurana, Giovanna E. Hidalgo, Aaron Shmookler, Aashutosh Tripathi, Cuiping Zhang, Joseph B. Zwischenberger, Francesc Marti

Markey Cancer Center Faculty Publications

The manufacturing process of regulatory T (Treg) cells for clinical application begins with the positive selection of CD25⁺ cells using superparamagnetic iron oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25–interleukin-2 receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with a concomitant decrease …

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …

The Carboxy Terminus Causes Interfacial Assembly Of Oleate Hydratase On A Membrane Bilayer, Christopher D. Radka, Christy R. Grace, Hale S. Hasdemir, Yupeng Li, Carlos C. Rodriguez, Patrick Rodrigues, Michael L. Oldham, M. Zuhaib Qayyum, Aaron Pitre, William J. Maccain, Ravi C. Kalathur, Emad Tajkhorshid, Charles O. Rock

Markey Cancer Center Faculty Publications

The soluble flavoprotein oleate hydratase (OhyA) hydrates the 9-cis double bond of unsaturated fatty acids. OhyA sub- strates are embedded in membrane bilayers; OhyA must remove the fatty acid from the bilayer and enclose it in the active site. Here, we show that the positively charged helix- turn-helix motif in the carboxy terminus (CTD) is responsible for interacting with the negatively charged phosphatidylgly- cerol (PG) bilayer. Super-resolution microscopy of Staphylo- coccus aureus cells expressing green fluorescent protein fused to OhyA or the CTD sequence shows subcellular localization along the cellular boundary, indicating OhyA is membrane- associated and the CTD sequence …

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …

Extended Conformations Of Bifurcating Electron Transfer Flavoprotein Constitute Up To Half The Population, Possibly Mediating Conformational Change, Sharique A. Khan, Alan Hicks, Wellington C. Leite, James Byrnes, Biswajit Gorai, Maria-Andrea Mroginski, Hugh O'Neill, Anne-Francis Miller

Markey Cancer Center Faculty Publications

Electron transfer bifurcation enables biological systems to drive unfavourable (endergonic) electron transfer by coupling it to favourable (exergonic) transfer of a second electron. In electron transfer flavoproteins (ETFs), a domain-scale conformational change is believed to sever the favourable pathway after a single electron has used it, thereby preventing the energy dissipation that would accompany exergonic transfer of the second electron. To understand the conformation change that participates in turnover, we have deployed small-angle neutron scattering (SANS) and computational techniques to characterize the bifurcating ETF from Acidaminococcus fermentans (AfeETF). SANS data reveal an overall radius of gyration (Rg) of 30.1 ± …

Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang

Markey Cancer Center Faculty Publications

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valu- able to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning meth- ods to predict a patient’s response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is …

Machine-Learning-Assisted Design Of Deep Eutectic Solvents Based On Uncovered Hydrogen Bond Patterns, Usman Lame Abbas, Yuxuan Zhang, Joseph Tapia, Md Selim, Jin Chen, Jian Shi, Qing Shao

Markey Cancer Center Faculty Publications

Non-ionic deep eutectic solvents (DESs) are non-ionic designer solvents with various applications in catalysis, extraction, carbon capture, and pharmaceuticals. However, discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation. The search for DES relies heavily on intuition or trial-and-error processes, leading to low success rates or missed opportuni- ties. Recognizing that hydrogen bonds (HBs) play a central role in DES formation, we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning (ML) models to discover new DES systems. We first analyze the …

Tyrp1 Is The Mendelian Determinant Of The Axolotl (Ambystoma Mexicanum) Copper Mutant, Raissa F. Cecil, Lloyd Strohl, Maddie K. Thomas, James L. Schwartz, Nataliya Timoshevskaya, Jeramiah J. Smith, S. Randal Voss

Markey Cancer Center Faculty Publications

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that …