Genetics and Genomics Commons^™

Synthetic Errα/Β/Γ Agonist Induces An Errα-Dependent Acute Aerobic Exercise Response And Enhances Exercise Capacity, Cyrielle Billon, Sadichha Sitaula, Subhashis Banerjee, Ryan Welch, Bahaa Elgendy, Lamees Hegazy, Tae Gyu Oh, Melissa Kazantzis, Arindam Chatterjee, John Chrivia, Matthew E Hayes, Weiyi Xu, Angelica Hamilton, Janice M Huss, Lilei Zhang, John K Walker, Michael Downes, Ronald M Evans, Thomas P Burris

Faculty, Staff and Students Publications

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that the orphan nuclear receptors estrogen receptor-related receptors (ERRs) play an important role in skeletal muscle exercise capacity. Three ERR subtypes exist (ERRα, β, and γ), and although ERRβ/γ agonists have been designed, there have been significant difficulties in designing compounds with ERRα agonist activity. Additionally, there are limited synthetic agonists that can be used to target ERRs in vivo. Here, we report the …

A Meta-Narrative Review: Efficacy Of Non-Invasive Prenatal Testing (Nipt) In The Detection Of Sex Chromosomal Aneuploidy In Singleton Pregnancy, Tien T. Dao, Arianna Fields, Annie Huynh, Nikkita Mcghee, Christian Pellegrini

Research Methods Poster Session 2023

Abstract:

Objective: To assess the efficacy of Noninvasive Prenatal Testing (NIPT) as a screening method for Sex Chromosomal Aneuploidy (SCA) and its application in clinical practice.

Methods: Searches on Pubmed and M.D. Anderson Cancer Center Research Medical Library was performed to identify primary research articles published between January 2018 to April 2023.

Results: The average combined SCA's PPV was 46.08%. The average PPV for 45, X, 47, XXX, 47, XXY, and 47, XYY was 26.05%, 44.82%, 50.21%, and 62.99%, respectively. The average PPV for 46, XY was 1.18%; however, there is a lack of statistical data for 46, XY. NIPT …

An Altered Extracellular Matrix-Integrin Interface Contributes To Huntington’S Disease-Associated Cns Dysfunction In Glial And Vascular Cells, Sarah J Hernandez, Ryan G Lim, Tarik Onur, Mark A Dane, Rebecca Smith, Keona Wang, Grace En-Hway Jean, Andrea Reyes-Ortiz, Kaylyn Devlin, Ricardo Miramontes, Jie Wu, Malcolm Casale, David Kilburn, Laura M Heiser, James E Korkola, David Van Vactor, Juan Botas, Katherine L Thompson-Peer, Leslie M Thompson

Faculty, Staff and Students Publications

Astrocytes and brain endothelial cells are components of the neurovascular unit that comprises the blood-brain barrier (BBB) and their dysfunction contributes to pathogenesis in Huntington's disease (HD). Defining the contribution of these cells to disease can inform cell-type-specific effects and uncover new disease-modifying therapeutic targets. These cells express integrin (ITG) adhesion receptors that anchor the cells to the extracellular matrix (ECM) to maintain the integrity of the BBB. We used HD patient-derived induced pluripotent stem cell (iPSC) modeling to study the ECM-ITG interface in astrocytes and brain microvascular endothelial cells and found ECM-ITG dysregulation in human iPSC-derived cells that may …

Influence Of Ambient Water Coloration On Habitat And Conspecific Choice In The Female Lake Malawi Cichlid, Metriaclima Zebra, Noori Choi, Nicolas Mathevon, Eileen A. Hebets, Marilyn Beauchaud

Eileen Hebets Publications

Female cichlid fish living in African great lakes are known to have sensory systems that are adapted to ambient light environments. These sensory system adaptations are hypothesized to have influenced the evolution of the diverse male nuptial coloration. In rock-dwelling Lake Malawi mbuna cichlids, however, the extent to which ambient light environments influence female sensory systems and potentially associated male nuptial coloration remains unknown. Yet, the ubiquitous blue flank coloration and UV reflection of male mbuna cichlids suggest the potential impacts of the blue-shifted ambient light environment on these cichlid’s visual perception and male nuptial coloration in the shallow water …

Sptssa Variants Alter Sphingolipid Synthesis And Cause A Complex Hereditary Spastic Paraplegia, Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K G Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C Spillmann, Undiagnosed Disease Network, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J Bellen, Simon Edvardson, Florian Eichler, Teresa M Dunn

Faculty, Staff and Students Publications

Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting …

The Presence Of Tetracycline-Resistant Bacteria In A Kean University Campus Soil Sample, Esther Blankson, Jessica Kobilas, Gianna Medeiros

Kean Quest

The spread of antimicrobial resistance (AMR) in the environment is a worldwide problem that threatens human health. Bacteria are becoming increasingly resistant to antibiotics as the consumption of antibiotics grows. In particular, soil can be contaminated with bacteria that are resistant to antibiotics. As of today, there is no surveillance system that tracks the spread of antibiotic-resistant bacteria, however, Tufts University aims to change this by implementing the Prevalence of Antibiotic Resistance in the Environment (PARE) project. The course-based PARE project consists of research students sampling soil in diverse locations and reporting the prevalence of antibiotic-resistant bacteria. The purpose of …

The Role Of Community In Immunity Against Sars-Cov-2, Jessica Kobilas

Kean Quest

This literature review investigated the roles genes activated by social interactions had in helping to build immunity against COVID-19. Past studies have shown that individuals who are more socially connected are less likely to become ill due to social interactions strengthening the immune system through optimal exposure to bacteria and viruses in the environment. The IL-6 and TLR4 genes that are activated through social interactions and associated with cytokines have been analyzed in cases of various viral infections. Cytokines play a role in inflammation and have both pro-inflammatory and anti-inflammatory responses to infections and viruses. The results suggest that the …

Pepquery2 Democratizes Public Ms Proteomics Data For Rapid Peptide Searching, Bo Wen, Bing Zhang

Faculty, Staff and Students Publications

We present PepQuery2, which leverages a new tandem mass spectrometry (MS/MS) data indexing approach to enable ultrafast, targeted identification of novel and known peptides in any local or publicly available MS proteomics datasets. The stand-alone version of PepQuery2 allows directly searching more than one billion indexed MS/MS spectra in the PepQueryDB or any public datasets from PRIDE, MassIVE, iProX, or jPOSTrepo, whereas the web version enables users to search datasets in PepQueryDB with a user-friendly interface. We demonstrate the utilities of PepQuery2 in a wide range of applications including detecting proteomic evidence for genomically predicted novel peptides, validating novel and …

Dataset Of Rna-Seq Transcriptome Of The Fetal Liver At Day 83 Of Gestation Associated With Periconceptual Maternal Nutrition In Beef Heifers, Wellison J.S. Diniz, Alison K. Ward, Kacie L. Mccathy, Cierrah J. Kassetas, Friederike Baumgaertner, Lawrence P. Reynolds, Pawel P. Borowicz, Kevin K. Sedivec, James D. Kirsch, Sheri T. Dorsam, Tammi L. Neville, J. Chris Forcherio, Ronald Scott, Joel S. Caton, Carl R. Dahlen

Department of Animal Science: Faculty Publications

Herein, we present a dataset based on the RNA-Seq analysis of liver tissue from bovine female fetuses at day 83 of gestation. The findings were reported in the main article, “Periconceptual maternal nutrition affects fetal liver programming of energy- and lipid-related genes”[1] . These data were generated to investigate the effects of periconceptual maternal vitamin and mineral supplementation and rates of body weight gain on the transcript abundance of genes associated with fetal hepatic metabolism and function. To this end, crossbred Angus beef heifers ( n = 35) were randomly assigned to 1 of 4 treatments in a 2 ×2 …

Ethnic-Specific Predictors Of Neurotoxicity Among Patients With Pediatric Acute Lymphoblastic Leukemia After High-Dose Methotrexate, Rachel D Harris, Melanie Brooke Bernhardt, Mark C Zobeck, Olga A Taylor, Maria Monica Gramatges, Eric S Schafer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Austin L Brown

Faculty, Staff and Students Publications

High-dose methotrexate (HD-MTX; 5,000 mg/m2) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity which may disproportionately affect Latino children. Thus, we evaluated risk factors for neurotoxicity in an ethnically diverse population of 351 patients (58.1% Latino) who received 1,183 HD-MTX infusions. Overall, thirty-five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, we found that serum creatinine elevations ≥50% of baseline were associated with a 3-fold increased odds (OR = 3.32, 95% CI: 0.98-11.21, p=0.05) for …

Remote Sensing In Mapping Biodiversity – A Case Study Of Epiphytic Lichen Communities, Ida Palmroos, Veera Norros, Sarita Keski-Saari, Janne Mäyrä, Topi Tanhuanpää, Sonja Kivinen, Juha Pykälä, Peter Kullberg, Timo Kumpula, Petteri Vihervaara

Aspen Bibliography

In boreal forests, European aspen (Populus tremula L.) is a keystone species that hosts a variety of accompanying species including epiphytic lichens. Forest management actions have led to a decrease in aspen abundance and subsequent loss of suitable habitats of epiphytic lichens. In this study, we evaluate the environmental responses of epiphytic lichen species richness and community composition on aspen, focusing on the potential of remote sensing by combined hyperspectral imaging and airborne laser scanning to identify suitable habitats for epiphytic lichens. We measured different substrate and habitat parameters in the field (e.g., aspen diameter and bark pH) …

Assessment Of Anti-Hiv-1 Guide Rna Efficacy In Cells Containing The Viral Target Sequence, Corresponding Grna, And Crispr/Cas9., Alexander G Allen, Cheng-Han Chung, Stephen D. Worrell, Glad Nwaozo, Rebekah Madrid, Anthony R. Mele, Will Dampier, Michael R. Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing system has been shown to be effective at inhibiting human immunodeficiency virus type 1 (HIV-1). Studies have not consistently used a trackable dual reporter system to determine what cells received the Cas9/gRNA to determine the overall knockdown of HIV. Some studies have used stably transduced cells under drug selection to accomplish this goal. Here a two-color system was used that allows tracking of viral protein expression and which cells received the CRISPR/Cas9 system. These experiments ensured that each gRNA used was a perfect match to the intended target to remove …

Precision Medicine, Ancestry, Genetics And Race, Lucio Miele

School of Medicine Faculty Publications

DiscoverBMB, March 25 - 28, 2023, Seattle, WA

Low And Differential Polygenic Score Generalizability Among African Populations Due Largely To Genetic Diversity, Lerato Majara, Allan Kalungi, Nastassja Koen, Kristin Tsuo, Ying Wang, Rahul Gupta, Lethukuthula L Nkambule, Heather Zar, Dan J Stein, Eugene Kinyanda, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRSs) in simulations across Africa and in empirical data from South Africa, Uganda, and the United Kingdom to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South African individuals, we find that PRS accuracy is low for all traits but varies across …

Physio-Psycho-Social Interaction Mechanism In Dyadic Health Of Young And Middle-Aged Stroke Survivors And Their Spousal Caregivers: A Longitudinal Observational Study Protocol, Dandan Xiang, Zhen-Xiang Zhang, Song Ge, Wen Na Wang, Bei-Lei Lin, Su-Yan Chen, Er-Feng Guo, Peng-Bo Zhang, Zhi-Wei Liu, Hui Li, Yong-Xia Mei

Faculty, Staff and Student Publications

Introduction: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. …

A Rare Metastatic Mesenteric Malignant Pecoma With Tsc2 Mutation Treated With Palliative Surgical Resection And Nab-Sirolimus: A Case Report, Luke Meredith, Timothy Chao, Avinoam Nevler, Atrayee Basu Mallick, Rajan Singla, Peter Mccue, Wilbur Bowne, Wei Jiang, Md, Phd

Kimmel Cancer Center Faculty Papers

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of …

Foxi3 Pathogenic Variants Cause One Form Of Craniofacial Microsomia, Ke Mao, Christelle Borel, Muhammad Ansar, Angad Jolly, Periklis Makrythanasis, Christine Froehlich, Justyna Iwaszkiewicz, Bingqing Wang, Xiaopeng Xu, Qiang Li, Xavier Blanc, Hao Zhu, Qi Chen, Fujun Jin, Harinarayana Ankamreddy, Sunita Singh, Hongyuan Zhang, Xiaogang Wang, Peiwei Chen, Emmanuelle Ranza, Sohail Aziz Paracha, Syed Fahim Shah, Valentina Guida, Francesca Piceci-Sparascio, Daniela Melis, Bruno Dallapiccola, Maria Cristina Digilio, Antonio Novelli, Monia Magliozzi, Maria Teresa Fadda, Haley Streff, Keren Machol, Richard A Lewis, Vincent Zoete, Gabriella Maria Squeo, Paolo Prontera, Giorgia Mancano, Giulia Gori, Milena Mariani, Angelo Selicorni, Stavroula Psoni, Helen Fryssira, Sofia Douzgou, Sandrine Marlin, Saskia Biskup, Alessandro De Luca, Giuseppe Merla, Shouqin Zhao, Timothy C Cox, Andrew K Groves, James R Lupski, Qingguo Zhang, Yong-Biao Zhang, Stylianos E Antonarakis

Faculty, Staff and Students Publications

Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in …

Genetic Markers And Tree Properties Predicting Wood Biorefining Potential In Aspen (Populus Tremula) Bioenergy Feedstock, Sacha Escamez, Kathryn M. Robinson, Mikko Luomaranta, Madhavi Latha Gandla, Niklas Mähler, Zakiya Yassin, Thomas Grahn, Gerhard Scheepers, Lars-Göran Stener, Stefan Jansson, Leif J. Jönsson, Nathaniel R. Street, Hannele Tuominen

Aspen Bibliography

Background Wood represents the majority of the biomass on land and constitutes a renewable source of biofuels and other bioproducts. However, wood is recalcitrant to bioconversion, raising a need for feedstock improvement in production of, for instance, biofuels. We investigated the properties of wood that affect bioconversion, as well as the underlying genetics, to help identify superior tree feedstocks for biorefining.

Results We recorded 65 wood-related and growth traits in a population of 113 natural aspen genotypes from Sweden (https://doi.org/10.5061/dryad.gtht76hrd). These traits included three growth and field performance traits, 20 traits for wood chemical composition, 17 traits for wood anatomy …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Physiological And Transcriptomic Responses Of Two Artemisia Californica Populations To Drought: Implications For Restoring Drought-Resilient Native Communities, Hagop S. Atamian Dr., Jennifer L. Funk

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

As climate change brings drier and more variable rainfall patterns to many arid and semi-arid regions, land managers must re-assemble appropriate plant communities for these conditions. Transcriptome sequencing can elucidate the molecular mechanisms underlying plant responses to changing environmental conditions, potentially enhancing our ability to screen suitable genotypes and species for restoration. We examined physiological and morphological traits and transcriptome sequences of coastal and inland populations of California sagebrush (Artemisia californica), a critical shrub used to restore coastal sage scrub vegetation communities, grown under low and high rainfall environments. The populations are located approximately 36 km apart but …