Genetics Commons^™

Discovery Of Novel Ubiquitin- And Methylation-Dependent Interactions Using Protein Domain Microarrays, Jianji Chen

Dissertations and Theses (Open Access)

Post-translational modifications (PTMs) drive signal transduction by interacting with "reader" proteins. Protein domain microarray is a high throughput platform to identify novel readers for PTMs. In this dissertation, I applied two protein domain microarrays identifying novel readers for histone H2Aub1 and H2Bub1, and H3TM K4me3. Ubiquitinations of histone H2A at K119 (H2Aub1) and histone H2B at K120 (H2Bub1) function in distinct transcription regulation and DNA damage repair pathways, likely mediated by specific "reader" proteins. There are only two H2Aub1-specific readers identified and no known H2Bub1-specific readers. Using a ubiquitin-binding domain microarray, I discovered the phospholipase A2-activating protein (PLAA) PFU domain …

Assessing Genetic Counselors' Clinical Approach And Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades, Grant Bonesteele

Dissertations and Theses (Open Access)

Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially challenging cases as a genetic counselor. Therefore, we aimed to characterize genetic counselors’ experiences, approach, and practices to variant downgrade cases using an online survey. The survey asked participants how they would approach variant downgrade scenarios involving the CDH1 or ATM genes with variable family histories. Genetic counselors appear to be united in whether they would …

Genetic Pathway Analysis Of Abnormal Facial Development In Nonsyndromic Cleft Lip And Palate, Lorena Maili

Dissertations and Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect resulting from incomplete fusion of the facial prominences during development, which leaves a gap in the lip, primary palate and/or the secondary palate. NSCLP affects 135,000 NSCLP newborns worldwide each year based on a birth prevalence of 1 per 700 live births. While surgical treatments have dramatically improved, many long-term health issues persist, imposing significant medical, psychosocial and economic burdens. Familial aggregation and segregation analyses suggest genetic contributions underlie NSCLP, but despite decades of study, only a small portion of the NSCLP genetic liability …

Investigating Barriers Experienced By Underrepresented Minorities In Becoming A Competitive Genetic Counseling Applicant, Katie Huang

Dissertations and Theses (Open Access)

Representation for both racial/ethnic and gender identity minorities in genetic counseling (GC) remains the lowest among similar healthcare professions. Barriers that underrepresented minority (URM) individuals face in becoming a competitive GC applicant have not yet been described. Academic capital (AC) is a theoretical framework describing the social processes necessary for individuals to navigate and succeed in higher education. This study aimed to characterize barriers experienced by applicants who self-identify as underrepresented and to explore how AC could identify areas for intervention. Prospective GC applicants for the 2021/2022 cycles were recruited to complete an anonymous online survey in Qualtrics through a …

Rare Variant Association Studies In Crohn’S Disease And Colorectal Cancer: Methods And Applications, Jiun-Sheng Chen

Dissertations and Theses (Open Access)

Genetic factors account for a substantial portion of Crohn’s disease and colorectal cancer (CRC) risk. Patients with Crohn’s disease, a condition that causes chronic inflammation of the gastrointestinal tract, are at increased risk of colorectal cancer morbidity and mortality. Genome-wide association studies using single marker approaches have identified loci responsible for these diseases, but disease susceptibility from rare variants is incompletely understood. This dissertation includes three chapters, two association studies for Crohn’s disease and CRC, and a statistical method to improve the power of statistical tests.

For Crohn’s disease, we performed targeted sequencing of 101 genes in 205 children with …

Molecular And Genetic Studies Of Robo2 Transcriptional Regulation In The Central Nervous System Of Drosophila Melanogaster, Muna Abdal Rahim Abdal Rhida

Graduate Theses and Dissertations

Drosophila Robo2 axon guidance receptor is a member of the evolutionarily conserved Roundabout (Robo) protein family that is involved in directing axons that cross the midline to the other side of the animal body. Robo2 roles mainly depend on two factors: The functional domains of the Robo2 protein, which is extensively studied, and the dynamic transcription of robo2 in various subsets of cells throughout embryogenesis which is not fully understood. Thus, knowing robo2 enhancers that transcriptionally regulate robo2 during embryogenesis is significant. To investigate robo2 potential enhancers, we screened 17 transgenic lines of Drosophila that were generated by Janelia Research …

Novel Genetic Mutations In Genes Agbl5 And Tulp1 For Presumed Unilateral Retinitis Pigmentosa Managed With Low Vision Rehabilitation: A Case Report And Review, Maggie Man Ki Ho Od, Ms, Faao, Stephanie Schmiedecke-Barbieri Od, Faao, Abcmo, Dip Low Vision, Patricia C. Sanchez-Diaz Phd, Dvm, Faao, Carolyn E. Majcher Od, Faao, Fors

Optometric Clinical Practice

Background: Retinitis pigmentosa is a group of hereditary retinal diseases characterized by the degeneration of rod and cone photoreceptors. It commonly results in night blindness followed by tunnel vision and central vision reduction. The classic triad of clinical signs includes pigmented bone spicules, waxy disc pallor, and arterial attenuation. Unilateral retinitis pigmentosa is rare and can be supported with ancillary testing including genetic and laboratory studies to rule out differential diagnoses.

Case Report: A 68-year-old Hispanic female was referred to the low vision rehabilitation clinic due to progressive vision loss in the left eye (OS) that began 15 years ago. …

Determination Of The Presence Of Rickettsia Spp. And Borrelia Spp. Carried By Tortoise Ticks From Madagascar, Anna Phan

Biological Sciences Theses & Dissertations

Ticks were removed from three species of Malagasy tortoises, Astrochelys yniphora, A. radiata, and Pyxis arachnoides (comprising two subspecies P. a. arachnoides and P. a. oblonga), between 2012 and 2015. The ticks were presumed to be from the genus Amblyomma. Ticks were morphologically identified and then checked molecularly to confirm their classification or identify any ticks that could not be morphologically identified. Molecular identification was done via end-point PCR that amplified tick cytochrome oxidase (CO1) and tick 12S rRNA genes. Ticks were screened via a real-time polymerase chain reaction assay for the presence of Rickettsia spp. …

Retinoblastoma: Past, Present, And Future, Izabela Daneva, Crysty-Ann Olaco, Albert Tran

Undergraduate Research Symposium Posters

The purpose of this research timeline is to synthesize the natural history of retinoblastoma to understand its societal effects and develop a public health message to raise awareness of the disease. We used literature-based research in order to gain an understanding about the discovery of this disease and investigate its most current state of knowledge. Retinoblastoma is an intraocular cancer that manifests early in childhood. It is typically linked to a somatic or germline insertion, deletion, or single-base substitution mutation on both alleles of RB1, a tumor-suppressor gene. Retinoblastoma was first identified in 1809 by James Wardrop, and since then, …

“Adopt-A-Tissue” Initiative Advances Efforts To Identify Tissue-Specific Histone Marks In The Mare, N. B. Kingsley, Natasha A. Hamilton, Gabriella Lindgren, Ludovic Orlando, Ernest Bailey, Samantha Brooks, Molly Mccue, Theodore S. Kalbfleisch, James N. Macleod, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Defining Codes Based On The Consolidated Framework For Implementation Research In The Context Of The Implementing Universal Lynch Syndrome Screening, Jasmine A. Burton-Akright

USF Tampa Graduate Theses and Dissertations

Lynch syndrome (LS) is the most common hereditary cause of both colorectal cancer (CRC) and endometrial cancer (EC). Universal tumor screening (UTS) of newly diagnosed EC and CRC patients has been shown to be both an effective and economical approach to identify patients with LS and subsequently reduce future cancer s for patients and their family members. Despite its efficacy, LS UTS has not been consistently adopted across hospital systems and existing programs vary widely in their structure and execution. The Implementing Universal Lynch Syndrome Screening (IMPULSS) study aims to determine the critical factors necessary for successful implementation of LS …

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Sars-Cov-2: An Investigation On Mutagenicity And Its Effects On Infectivity And Mortality, Tyler Elliott Silverwood

Honors Theses and Capstones

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, has rapidly become a worldwide public health concern. Classified as a betacoronavirus, it is the third human coronavirus (HCoV) to emerge in the 21st century that causes severe disease, alongside SARS-CoV and MERS-CoV. The genome consists of open reading frames encoding accessory proteins and four structural proteins, including the spike protein which is a key determinant of host cell tropism. Mutations within the genome, particularly the spike gene, have been linked in-vitro to increased binding affinity to the human receptor angiotensin-converting enzyme 2 (hACE2), increased fitness in human hosts, and immune evasion. …

Mimicking The Effect Of Prolactin On Stat3/Stat5 Activity In Breast Cancer, Jennifer N. Barbuto, Sarah R. Walker

Honors Theses and Capstones

Signal transducers and activators of transcription (STAT) 3 and 5 are commonly constitutively activated in breast cancer. STAT5 can outcompete STAT3 and reduce cell proliferation and metastasis. STAT5 activation is stimulated by prolactin, a natural hormone that can be harmful at high levels. The aim of this study is to identify some possible previously developed drugs that mimic the effect of prolactin and STAT5 without the added risk in MDA-MB231 breast cancer cells. Using the CLUE database query app and STAT5 up- and downregulation signatures, three drugs (X, K, and M) were chosen based on their similarity in signatures to …

In Silico Investigation Of Cardiac Arrhythmia Susceptibility In Long Qt Phenotype, Anthony Owusu-Mensah, Victoria Lam, Bright Tsevi, Michel Audette, Makarand Deo

Electrical & Computer Engineering Faculty Publications

Long QT Syndrome (LQTS) is associated with cardiac arrhythmia and sudden cardiac death. The Long QT Type 2 (LQT2) phenotype, which accounts for 35–40 % of all LQTS patients, is caused by mutations in HERG gene. The mechanisms of arrhythmia in presence of LQT2 conditions are not fully understood. We utilized anatomically and electrophysiologically realistic numerical simulations to elucidate the mechanisms of arrhythmia initiation in presence of blockade in rapid component of delayed rectifier potassium current, I_Kr. We utilized a 3D finite element model of rabbit ventricles integrated with His-purkinje network to simulate whole heart response to LQT2 …

Joint Modeling Of Rnaseq And Radiomics Data For Glioma Molecular Characterization And Prediction, Zeina A. Shboul, Norou Diawara, Arastoo Vossough, James Y. Chen, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. …

Microbiomes Of Blood-Feeding Arthropods: Genes Coding For Essential Nutrients And Relation To Vector Fitness And Pathogenic Infections. A Review, Daniel E. Sonenshine, Philip E. Stewart

Biological Sciences Faculty Publications

Blood-feeding arthropods support a diverse array of symbiotic microbes, some of which facilitate host growth and development whereas others are detrimental to vector-borne pathogens. We found a common core constituency among the microbiota of 16 different arthropod blood-sucking disease vectors, including Bacillaceae, Rickettsiaceae, Anaplasmataceae, Sphingomonadaceae, Enterobacteriaceae, Pseudomonadaceae, Moraxellaceae and Staphylococcaceae. By comparing 21 genomes of common bacterial symbionts in blood-feeding vectors versus non-blooding insects, we found that certain enteric bacteria benefit their hosts by upregulating numerous genes coding for essential nutrients. Bacteria of blood-sucking vectors expressed significantly more genes (p < 0.001) coding for these essential nutrients than those of non-blooding insects. Moreover, compared to endosymbionts, the genomes of enteric bacteria also contained significantly more genes (p < 0.001) that code for the synthesis of essential amino acids and proteins that detoxify reactive oxygen species. In contrast, microbes in non-blood-feeding insects expressed few gene families coding for these nutrient categories. We also discuss specific midgut bacteria essential for the normal development of pathogens (e.g., Leishmania) versus …

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 …

Novel Mutations In The Gtpbp3 Gene For Mitochondrial Disease And Characteristics Of Related Phenotypic Spectrum: The First Three Cases From China, Hui-Ming Yan, Zhi-Mei Liu, Bei Cao, Victor Wei Zhang, Yi-Duo He, Zheng-Jun Jia, Hui Xi, Jing Liu, Fang Fang, Hua Wang

Faculty, Staff and Students Publications

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3 …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Genetic And Clinical Determinants Of Racial/Ethnic Differences In Multiple Myeloma Susceptibility And Outcomes Focusing On Hispanics, Alem Belachew

Dissertations and Theses (Open Access)

Multiple Myeloma (MM) constitutes 10% of diagnosed hematologic malignancies in the US, with over 12,000 deaths recorded each year. Race/ethnicity is a well-known MM risk factor, where individuals of African descent have over 2- to 3-fold increased risk of incidence compared to those of European descent. Additionally, Hispanics are diagnosed approximately three years younger than white American counterparts, for unknown reasons. Differences in clinical phenotype are also present for MM patients by ancestry, including varying rates of common initiation mutations such as IgH translocations and TP53 mutation between patients of European and African descent. Studies have begun to interrogate the …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations and Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Versatile Phenotype-Activated Cell Sorting, Jihwan Lee, Zhuohe Liu, Peter H Suzuki, John F Ahrens, Shujuan Lai, Xiaoyu Lu, Sihui Guan, François St-Pierre

Faculty, Staff and Students Publications

Unraveling the genetic and epigenetic determinants of phenotypes is critical for understanding and re-engineering biology and would benefit from improved methods to separate cells based on phenotypes. Here, we report SPOTlight, a versatile high-throughput technique to isolate individual yeast or human cells with unique spatiotemporal profiles from heterogeneous populations. SPOTlight relies on imaging visual phenotypes by microscopy, precise optical tagging of single target cells, and retrieval of tagged cells by fluorescence-activated cell sorting. To illustrate SPOTlight's ability to screen cells based on temporal properties, we chose to develop a photostable yellow fluorescent protein for extended imaging experiments. We screened 3 …

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration …

The P-Glycoprotein Repertoire Of The Equine Parasitic Nematode Parascaris Univalens, Alexander P. Gerhard, Jürgen Krücken, Emanuel Heitlinger, I. Jana I. Janssen, Marta Basiaga, Sławomir Kornaś, Céline Beier, Martin K. Nielsen, Richard E. Davis, Jianbin Wang, Georg Von Samson-Himmelstjerna

Maxwell H. Gluck Equine Research Center Faculty Publications

P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the major site of expression but individual gene expression patterns were not conserved between the two nematodes. In P. …

A Novel Serpinb1 Single-Nucleotide Polymorphism Associated With Glycemic Control And Β-Cell Function In Egyptian Type 2 Diabetic Patients, Dina H. Kassem, Aya Adel, Ghada H. Sayed, Mohamed M. Kamal

Pharmacy

Aims: Serine protease inhibitor B1 (SerpinB1) is a neutrophil elastase inhibitor that has been proved to be associated with type 2 diabetes mellitus and pancreatic β-cell proliferation. In this study, we investigated 2 SERPINB1 SNPs, rs114597282 and rs15286, regarding their association with diabetes risk and various anthropometric and biochemical parameters in Egyptian type 2 diabetic patients.

Materials and Methods: A total of 160 subjects (62 control and 98 type 2 diabetic patients) participated in this study. Various anthropometric and biochemical parameters were assessed. Genotyping assay for the two SNPs was done using TaqMan genotyping assays. The association of rs15286 variants …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

Identifying Pleiotropic Snps Associated With Femoral Neck And Heel Bone Mineral Density, Pei He, Xinag-He Ming, Xiao Zhang, Xu Lin, Qiang Zhang, Ri-Li Jiang, Martin R. Schiller, Fei-Yan Deng, Hong-Wen Deng

Life Sciences Faculty Research

Background: Genome-wide association studies (GWASs) routinely identify loci associated with risk factors for osteoporosis. However, GWASs with relatively small sample sizes still lack sufficient power to ascertain the majority of genetic variants with small to modest effect size, which may together truly influence the phenotype. The loci identified only account for a small percentage of the heritability of osteoporosis. This study aims to identify novel genetic loci associated with DXA-derived femoral neck (FNK) bone mineral density (BMD) and quantitative ultrasound of the heel calcaneus estimated BMD (eBMD), and to detect shared/causal variants for the two traits, to assess whether the …

An Epistatic Interaction Between Pre-Natal Smoke Exposure And Socioeconomic Status Has A Significant Impact On Bronchodilator Drug Response In African American Youth With Asthma., J Magaña, M G Contreras, K L Keys, O Risse-Adams, P C Goddard, A M Zeiger, A C Y Mak, J R Elhawary, L A Samedy-Bates, E Lee, N Thakur, D Hu, C Eng, S Salazar, S Huntsman, T Hu, E G Burchard, M J White

Department of Medicine Faculty Papers

Background: Asthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate …

Aav-Crispr Gene Editing Is Negated By Pre-Existing Immunity To Cas9, Ang Li, Mark R Tanner, Ciaran M Lee, Ayrea E Hurley, Marco De Giorgi, Kelsey E Jarrett, Timothy H Davis, Alexandria M Doerfler, Gang Bao, Christine Beeton, William R Lagor

Faculty, Staff and Students Publications

Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by …