Medical Genetics Commons^™

Bridging The Gap: Transforming Primary Care Through The Artificial Intelligence And Machine Learning For Primary Care (Aim-Pc) Curriculum, Winston Liaw, Brian Hischier, Cornelius A James, Ioannis Kakadiaris, Jacqueline K Kueper, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Rragd-Associated Autosomal Dominant Kidney Hypomagnesemia With Cardiomyopathy: A Review On The Clinical Manifestations And Therapeutic Options, Francesco Trepiccione, Irene Sambri, Barbara Ruggiero, Francesco Emma, Andrea Ballabio, Giulia Florio, Ines Vanderheyden, Anna Iervolino, François Jouret

Duncan NRI Faculty and Staff Publications

Background: A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated autosomal dominant kidney hypomagnesemia with cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mechanistic target of rapamycin complex 1 pathway. This disruption hinders the nuclear translocation and transcriptional activity of the transcription factor EB a crucial regulator of lysosomal and autophagic function.

Summary: All identified RRAGD variants compromise …

Development Of A Multi-Level/Multi-Modal Intervention For Health Care Transition Preparation, Beth H Garland, Mary Majumder, Constance M Wiemann, Blanca Sanchez-Fournier, Jordyn Babla, Albert C Hergenroeder

Center for Medical Ethics and Health Policy Staff Publications

Aims: Health care transition (HCT) to adult care and young adult disease self-management is a multi-step process involving three major stakeholders - the adolescent, the caregiver, and the provider. Preparation gaps exist within each of these stakeholder groups. This paper presents the development of the Intervention to Promote Autonomy and Competence in Transition-aged Youth (IPACT), a multi-level (adolescent, caregiver, provider), multi-modal (interactive skill building sessions, educational materials, videos) intervention to address gaps in all three stakeholder groups simultaneously and help support achieving the three core elements of HCT planning.

Methods: Eight processes were utilized to develop the IPACT intervention, including …

Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng

Faculty, Staff and Student Publications

Sle1 and Fas^lpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Fas^lpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Fas^lpr/+ (Sle1homo.lprhet) and compared it with B6.Fas^lpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Fas^lpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly …

Understanding Primary Care Physician Perspectives On The Diagnosis And Management Of Non-Alcoholic Fatty Liver Disease: A Qualitative Study, Natalia I Heredia, Jemima C John, Sonia Singh, Jessica P Hwang, Larkin L Strong, Maya Balakrishnan, Lorna H Mcneill

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are well suited to manage patients with non-alcoholic fatty liver disease (NAFLD), but the limited, existing research suggests inadequate knowledge about the natural history, diagnostic methods, and management of NAFLD. The purpose of this qualitative study is to further understand the knowledge and practices for the diagnosis and management of NAFLD among PCPs. We conducted in-depth interviews with PCPs in the Greater Houston area, addressing current clinical practices used for diagnosing and managing NAFLD, as well as the perceptions of the PCPs regarding the burden of NAFLD on patients. We recorded interviews, transcribed them, coded transcripts, …

Public Perspectives On Investigative Genetic Genealogy: Findings From A National Focus Group Study, Jacklyn Dahlquist, Jill O Robinson, Amira Daoud, Whitney Bash-Brooks, Amy L Mcguire, Christi J Guerrini, Stephanie M Fullerton

Center for Medical Ethics and Health Policy Staff Publications

Background: Investigative genetic genealogy (IGG) is a technique that involves uploading genotypes developed from perpetrator DNA left at a crime scene, or DNA from unidentified remains, to public genetic genealogy databases to identify genetic relatives and, through the creation of a family tree, the individual who was the source of the DNA. As policymakers demonstrate interest in regulating IGG, it is important to understand public perspectives on IGG to determine whether proposed policies are aligned with public attitudes.

Methods: We conducted eight focus groups with members of the public (N = 72), sampled from four geographically diverse US regions, …

"A Double-Edged Sword": A Brief History Of Genomic Data Governance And Genetic Researcher Perspectives On Data Sharing, Kayte Spector-Bagdady, Kerry A Ryan, Amy L Mcguire, Chris D Krenz, M Grace Trinidad, Kaitlyn Jaffe, Amanda Greene, J Denard Thomas, Madison Kent, Stephanie Morain, David Wilborn, J Scott Roberts

Center for Medical Ethics and Health Policy Staff Publications

As the federal government continues to expand upon and improve its data sharing policies over the past 20 years, complex challenges remain. Our interviews with U.S. academic genetic researchers (n=23) found that the burden, translation, industry limitations, and consent structure of data sharing remain major governance challenges.

Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson

Electronic Theses & Dissertations (2024 - present)

Fibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways …

De Novo Missense Variants In Zbtb47 Are Associated With Developmental Delays, Hypotonia, Seizures, Gait Abnormalities, And Variable Movement Abnormalities, Scott K Ward, Alexandrea Wadley, Chun-Hui Anne Tsai, Paul J Benke, Lisa Emrick, Kristen Fisher, Kimberly M Houck, Hongzheng Dai, Undiagnosed Diseases Network, Maria J Guillen Sacoto, William Craigen, Kimberly Glaser, David R Murdock, Luis Rohena, Karin E M Diderich, Hennie T Bruggenwirth, Brendan Lee, Carlos Bacino, Lindsay C Burrage, Jill A Rosenfeld

Faculty, Staff and Students Publications

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders. All five patients are heterozygous for a de novo missense variant in ZBTB47, with p.(Glu680Gly) (c.2039A>G) detected …

The Challenges And Opportunities Of Offering And Integrating Training In Clinical Molecular Genetics And Clinical Cytogenetics: A Survey Of Lgg Fellowship Program Directors, Joshua L Deignan, Vimla Aggarwal, Allen E Bale, Daniel B Bellissimo, Jessica K Booker, Yang Cao, Kristy R Crooks, Kristen L Deak, Daniela Del Gaudio, Birgit Funke, Nicole L Hoppman, Vanessa Horner, Robert B Hufnagel, Colleen Jackson-Cook, Prasad Koduru, Marco L Leung, Shibo Li, Pengfei Liu, Minjie Luo, Rong Mao, Heather Mason-Suares, Fady M Mikhail, Stephen R Moore, Rizwan C Naeem, Laura M Pollard, Elena A Repnikova, Lina Shao, Brandon M Shaw, Shashirekha Shetty, Teresa A Smolarek, Elizabeth Spiteri, Jessica Van Ziffle, Gail H Vance, Cindy L Vnencak-Jones, Eli S Williams

Faculty, Staff and Students Publications

PURPOSE: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model.

METHODS: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data …

Neuronal Ablation Of Ghsr Mitigates Diet-Induced Depression And Memory Impairment Via Ampk-Autophagy Signaling-Mediated Inflammation, Hongying Wang, Zheng Shen, Chia-Shan Wu, Pengfei Ji, Ji Yeon Noh, Cédric G Geoffroy, Sunja Kim, David Threadgill, Jianrong Li, Yu Zhou, Xiaoqiu Xiao, Hui Zheng, Yuxiang Sun

Faculty, Staff and Students Publications

Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the …

Combined Bioinformatic And Splicing Analysis Of Likely Benign Intronic And Synonymous Variants Reveals Evidence For Pathogenicity, Owen R Hirschi, Stephanie A Felker, Surya P Rednam, Kelly L Vallance, D Williams Parsons, Angshumoy Roy, Gregory M Cooper, Sharon E Plon

Faculty, Staff and Students Publications

PURPOSE: Clinical variant analysis pipelines likely have poor sensitivity to the effects on splicing from variants beyond 10 to 20 bases of exon-intron boundaries. Here, we demonstrate the value of SpliceAI to inform curation of rare variants previously classified as benign/likely benign (B/LB) under current guidelines.

METHODS: Exome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.20), and scored >10 by combined annotation-dependent depletion. Rare synonymous or intronic B/LB variants in 61 genes submitted to ClinVar were …

Variations In The Germinal Center Response Revealed By Genetically Diverse Mouse Strains, Anne Marie Aubin, Daria Vdovenko, Roxanne Collin, Lois Balmer, Lise Coderre, Grant Morahan, Félix Lombard-Vadnais, Sylvie Lesage

Research outputs 2022 to 2026

The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we …

Steroid Receptor Coactivators In Treg And Th17 Cell Biology And Function, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.

Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang

Faculty, Staff and Students Publications

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of …

High Prevalence Of A-Β+ Ketosis-Prone Diabetes In Children With Type 2 Diabetes And Diabetic Ketoacidosis At Diagnosis: Evidence From The Rare And Atypical Diabetes Network (Radiant), Elizabeth Kubota-Mishra, Xiaofan Huang, Charles G Minard, Marcela Astudillo, Ahmad Refaey, Graciela Montes, Stephanie Sisley, Nalini Ram, William E Winter, Rochelle N Naylor, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur, Radiant Study Group

Faculty, Staff and Students Publications

BACKGROUND:A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at “T2D” onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort.

METHODS: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the …

Dna Mismatch Repair Defect And Intratumor Heterogeneous Deficiency Differently Impact Immune Responses In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Cancan Luo, Li Yu, Yong Li, Govind Bhagat, Alexandar Tzankov, Carlo Visco, Xiangshan Fan, Karen Dybkaer, Ali Sakhdari, Nicholas T Wang, Alyssa F Yuan, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Anamarija M Perry, Wenting Song, Dennis O'Malley, Qingyan Au, Harry Nunns, Heounjeong Go, Michael B Møller, Benjamin M Parsons, Santiago Montes-Moreno, Maurilio Ponzoni, Andrés J M Ferreri, Aliyah R Sohani, Jeremy S Abramson, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression …

Case Report: An Association Of Left Ventricular Outflow Tract Obstruction With 5p Deletions, Kira Mascho, Svetlana A Yatsenko, Cecilia W Lo, Xinxiu Xu, Jennifer Johnson, Lindsey R Helvaty, Stephanie Burns Wechsler, Chaya N Murali, Seema R Lalani, Vidu Garg, Jennelle C Hodge, Kim L Mcbride, Stephanie M Ware, Jiuann-Huey Ivy Lin

Faculty, Staff and Students Publications

INTRODUCTION: 5p deletion syndrome, also called Cri-du-chat syndrome 5p is a rare genetic syndrome with reports up to 36% of patients are associated with congenital heart defects. We investigated the association between left outflow tract obstruction and Cri-du-chat syndrome.

METHODS: A retrospective review of the abnormal microarray cases with congenital heart defects in Children's Hospital of Pittsburgh and the Cytogenomics of Cardiovascular Malformations Consortium.

RESULTS: A retrospective review at nine pediatric centers identified 4 patients with 5p deletions and left outflow tract obstruction (LVOTO). Three of these patients had additional copy number variants. We present data suggesting an association of …

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

Faculty, Staff and Students Publications

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

Research Participants' Perspectives On Precision Diagnostics For Alzheimer's Disease, Hadley Stevens Smith, Jill O Robinson, Ariel Levchenko, Stacey Pereira, Belen Pascual, Kathleen Bradbury, Victoria Arbones, Jamie Fong, Joshua M Shulman, Amy L Mcguire, Joseph Masdeu

Faculty, Staff and Students Publications

BACKGROUND: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

OBJECTIVE: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

METHODS: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results. We analyzed responses …

The Next-Generation Dna Vaccine Platforms And Delivery Systems: Advances, Challenges And Prospects, Bowen Lu, Jing Ming Lim, Boyue Yu, Siyuan Song, Praveen Neeli, Navid Sobhani, Pavithra K, Srinivasa Reddy Bonam, Rajendra Kurapati, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. …

Scientific Impact Of The National Birth Defects Prevention Network Multistate Collaborative Publications, Jacqueline T Bascom, Sara B Stephens, Philip J Lupo, Mark A Canfield, Russell S Kirby, Eirini Nestoridi, Jason L Salemi, Cara T Mai, Wendy N Nembhard, Nina E Forestieri, Paul A Romitti, Amanda M St Louis, A J Agopian

Faculty, Staff and Students Publications

BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact.

METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated.

RESULTS: …

A Comprehensive Analysis Of Neuroblastoma Incidence, Survival, And Racial And Ethnic Disparities From 2001 To 2019, Kevin Campbell, David A Siegel, Puja J Umaretiya, Shifan Dai, Andras Heczey, Philip J Lupo, Jeremy M Schraw, Trevor D Thompson, Michael E Scheurer, Jennifer H Foster

Faculty, Staff and Students Publications

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR).

METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI).

RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per …

Neutrophil-Derived Activin-A Moderates Their Pro-Netotic Activity And Attenuates Collateral Tissue Damage Caused By Influenza A Virus Infection, Georgios Divolis, Evgenia Synolaki, Athanasia Doulou, Ariana Gavriil, Christina C Giannouli, Anastasia Apostolidou, Martyn L Foster, Martin M Matzuk, Panagiotis Skendros, Ioanna-Evdokia Galani, Paschalis Sideras

Faculty, Staff and Students Publications

BACKGROUND: Pre-neutrophils, while developing in the bone marrow, transcribe the Inhba gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood.

METHODS:To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (S100a8-Cre/Inhba fl/fl mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Cffdna Screening For Niemann-Pick Disease, Type C1: A Case Series, Sydney A Lau, Romy I Fawaz, Robert Rigobello, Shahad Bawazeer, Nouf M Alajaji, Eissa Faqeih, Yanchun Li, Yanming Feng, Fan Xia, Christine M Eng, Malak Abedalthagafi

Faculty, Staff and Students Publications

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann-Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or …

Human Plcg2 Haploinsufficiency Results In A Novel Natural Killer Cell Immunodeficiency, Joshua B Alinger, Emily M Mace, Justin R Porter, Annelise Y Mah-Som, Allyssa L Daugherty, Stephanie Li, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Albert Yao, Ivan K Chinn, James R Lupski, Mohammad Ehlayel, Michael Keller, Greg R Bowman, Megan A Cooper, Jordan S Orange, Anthony R French

Faculty, Staff and Students Publications

Background:

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in NK cells, lymphocytes which recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK cell and B cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date.

Objective:

We aimed to identify the genetic cause of NK cell immunodeficiency in two families, and herein describe the functional consequences of two novel loss-of-function …

Comparative Exploration Of Mammalian Deafness Gene Homologues In The Drosophila Auditory Organ Shows Genetic Correlation Between Insect And Vertebrate Hearing, Daniel C Sutton, Jonathan C Andrews, Dylan M Dolezal, Ye Jin Park, Hongjie Li, Daniel F Eberl, Shinya Yamamoto, Andrew K Groves

Faculty, Staff and Students Publications

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to …

Improved Sequence Mapping Using A Complete Reference Genome And Lift-Over, Nae-Chyun Chen, Luis F Paulin, Fritz J Sedlazeck, Sergey Koren, Adam M Phillippy, Ben Langmead

Faculty, Staff and Students Publications

Complete, telomere-to-telomere genome assemblies promise improved analyses and the discovery of new variants, but many essential genomic resources remain associated with older reference genomes. Thus, there is a need to translate genomic features and read alignments between references. Here we describe a new method called levioSAM2 that accounts for reference changes and performs fast and accurate lift-over between assemblies using a whole-genome map. In addition to enabling the use of multiple references, we demonstrate that aligning reads to a high-quality reference (e.g. T2T-CHM13) and lifting to an older reference (e.g. GRCh38) actually improves the accuracy of the resulting variant calls …