Medicine and Health Sciences Commons^™

Genetic Separation Of Brca1 Functions Reveal Mutation-Dependent Polθ Vulnerabilities, John J. Krais, David J. Glass, Ilse Chudoba, Yifan Wang, Wanjuan Feng, Dennis Simpson, Pooja Patel, Zemin Liu, Ryan Neumann-Domer, Robert G. Betsch, Andrea J. Bernhardy, Alice M. Bradbury, Jason Conger, Wei-Ting Yueh, Joseph Nacson, Richard T. Pomerantz, Gaorav P. Gupta, Joseph R. Testa, Neil Johnson

Department of Biochemistry and Molecular Biology Faculty Papers

Homologous recombination (HR)-deficiency induces a dependency on DNA polymerase theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for cancer therapy. BRCA1 and BRCA2 deficient cells are thought to be synthetic lethal with Polθ, but whether distinct HR gene mutations give rise to equivalent Polθ-dependence, and the events that drive lethality, are unclear. In this study, we utilized mouse models with separate Brca1 functional defects to mechanistically define Brca1-Polθ synthetic lethality. Surprisingly, homozygous Brca1 mutant, Polq−/− cells were viable, but grew slowly and had chromosomal instability. Brca1 mutant cells proficient in DNA end resection were …

Analyzing Prominent Genes In Acute Lymphocytic Leukemia (All), Shima Z. Omar

Honors College Theses

Acute lymphocytic leukemia (ALL) is the most common type of childhood cancer. Leukemia is a type of cancer that involves the bone marrow and blood. This research study examined prominent genes in the disease. Two groups of genes, tumor suppressor and cell differentiation, were compared using statistical analysis to compare their binding potential and epigenetic potential. It is most likely that I failed to detect significant differences either because these genes’ function in the disease etiology is not strongly contexed to changes in expression, or that the magnitude of the differences were too slight to be detected with these methods. …

Atypical Intraparenchymal Meningioma With Yap1-Maml2 Fusion In A Young Adult Male: A Case Report And Mini Literature Review., Alisa Nobee, Mei Xu, Anjali Seth, Yuan Rong

PCOM Scholarly Papers

Oncogenic Yes-associated protein (YAP) 1 fusions have been recently identified in several cases of meningioma mostly involving pediatric patients. The meningiomas harboring YAP1-MAML2, which is the most frequent fusion subtype, exhibit activated YAP1 signaling and share similarities with NF2 (neurofibromatosis type 2 gene) mutant meningiomas. We reported a rare case of atypical intraparenchymal meningioma with YAP1-MAML2 fusion in a 20-year-old male. The patient presented with an episode of seizure without a medical history. MRI revealed a lesion in the right temporal lobe without extra-axial involvement. The radiological and morphological findings, however, were indistinctive from other intracranial diseases, e.g., vascular malformation …

A Genome-Wide Snp Investigation Of Chemical Intolerance, Raymond F. Palmer, Marcio Almeida, Roger B. Perales, Rudy Rincon

School of Medicine Publications and Presentations

Background

Chemical Intolerance (CI) also known as Multiple Chemical Sensitivity (MCS) is characterized by multi-system symptoms initiated by exposures to environmental toxins. Symptoms include fatigue, headache, mood changes, musculoskeletal pain, gastro-intestinal issues, and difficulties with memory/concentration. With mixed results, researchers have targeted specific genes to understand the genetic pathways associated with CI. This study is the first to apply a genome-wide, untargeted exploratory method.

Methods

A high-density genotyping platform was used to perform a hypothesis-free search for genetic variants associated with CI in a set of 200 participants. Each CI patient was verified using a validated survey. The association between …

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G. Izquierdo, Jing Chen, Richard Packer, Robert J. Hall, Anna L. Guyatt, Chiara Batini, Rebecca J. Thompson, Chandan Puvuluri, Vidhi Malik, Brian D. Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A. Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Sinjini Sikdar, Martin D. Tobin, Et Al.

Mathematics & Statistics Faculty Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

The Influence Of Genetics, Insulin Resistance, Oxidative Stress, And Energy Deficit On Migraine, Victoria Dm Maldonado Llinas

Honors Undergraduate Theses

The pathomechanism of migraine attacks is not understood well, however, is currently believed to be a brain disorder. Migraine is a multifactorial disorder that needs to be investigated in multiple research areas to shed light into its mechanism and find ways to treat it effectively. Migraine episodes come from one or many things at the same time, and such vary from person to person. However, sufficient evidence in recent studies show there is a strong relationship between genetics with patients having specific genes that may be responsible for the disease or a genetic sequence passed down through generations in families, …

Genetic Variants Within Noggin, Col1a1, Col5a1, And Igf2 Are Associated With Musculoskeletal Injuries In Elite Male Australian Football League Players: A Preliminary Study, Ysabel Jacob, Ryan S. Anderton, Jodie L. Cochrane Wilkie, Brent Rogalski, Simon M. Laws, Anthony Jones, Tania Spiteri, Dana Hince, Nicolas H. Hart

Research outputs 2022 to 2026

Introduction:

Australian Football is a dynamic team sport that requires many athletic traits to succeed. Due to this combination of traits, as well as technical skill and physicality, there are many types of injuries that could occur. Injuries are not only a hindrance to the individual player, but to the team as a whole. Many strength and conditioning personnel strive to minimise injuries to players to accomplish team success.

Purpose:

To investigate whether selected polymorphisms have an association with injury occurrence in elite male Australian Football players.

Methods:

Using DNA obtained from 46 elite male players, we investigated the associations …

Mendelian Gene Identification Through Mouse Embryo Viability Screening., Pilar Cacheiro, Carl Henrik Westerberg, Jesse Mager, Mary E Dickinson, Lauryl M J Nutter, Violeta Muñoz-Fuentes, Chih-Wei Hsu, Ignatia B Van Den Veyver, Ann M Flenniken, Colin Mckerlie, Stephen A Murray, Lydia Teboul, Jason D Heaney, K C Kent Lloyd, Louise Lanoue, Robert E Braun, Jacqueline K White, Amie K Creighton, Valerie Laurin, Ruolin Guo, Dawei Qu, Sara Wells, James Cleak, Rosie Bunton-Stasyshyn, Michelle Stewart, Jackie Harrisson, Jeremy Mason, Hamed Haseli Mashhadi, Helen Parkinson, Ann-Marie Mallon, International Mouse Phenotyping Consortium, Genomics England Research Consortium, Damian Smedley

Faculty Research 2022

BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property.

METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous …

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, …

Baroreflex Sensitivity In Facioscapulohumeral Muscular Dystrophy, Miguel Anselmo, Shandon Coffman, Mia Larson, Kathryn Vera, Emma Lee, Mary Mcconville, Michael Kyba, Manda L Keller-Ross

Department of Medicine Faculty Papers

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg …

Gene Expression And Doppler Flowmetry Of The Reproductive Tract In Nelore (Bos Indicus)Cows Synchronized With Estradiol And Equine Chorionic Gonadotrophin, Itamara Gomes De França, Nancyleni Pinto Cahves Bezerra, Alcina Vieira Carvalho Neta, Larissa Sarmento Santos, Diego Luiz Ds Santos Ribeiro, Jose Ribamar S Torres Junior

Turkish Journal of Veterinary & Animal Sciences

Forty Nelore cows were submitted to timed artificial insemination (TAI) protocol and randomly assigned to groups according to estradiol (E2) ester (cypionate or benzoate, i.e. EC or EB) and equine chorionic gonadotrophin treatment (eCG or No-eCG) in a factorial 2x2 design. On a random day of the estrous cycle (Day 0), cows received a P4 intravaginal device plus 2 mg im injection of EB. At the time of P4 device removal (Day 8), cows were treated with 0.150 mg im of D-cloprostenol (PGF) and randomly divided to receive or not 400 UI im of eCG, as well as randomly assigned …

Concordance Between Antibiotic Resistance Genes By Multiplex Polymerase Chain Reaction And Antibiotic Susceptibility By Pooled Antibiotic Sensitivity Testing In Symptomatic Patients With Urinary Tract Infection, Annah Vollstedt, Dakun Wang, Natalie Luke, David Baunoch, Kirk J. Wojno, Howard Korman, Natalie Gaines, Shuguang Huang, S Mohammad Jafri, David Wenzler, Patrick Cacdac, Frank Burks, Larry Sirls

Conference Presentation Abstracts

Introduction: Studies have shown many genes influence antibiotic resistance, and the relationship between genotypic and phenotypic antibiotic resistance is unclear. We sought to analyze the concordance between the presence of antibiotic resistance (ABR) genes and antibiotic susceptibility results. Methods: Urine samples were collected from patients presenting with possible UTI to 37 Urology clinics from July 2018 to February 2019. Multiplex polymerase chain reaction (M-PCR) was used to test for 33 ABR genes. Pooled Antibiotic Susceptibility Testing (P-AST) was performed against 14 different antibiotics. The concordance rate between the ABR genes and P-AST results was generated. The concordance rates for each …

Whole Genome Sequence Analysis Of Platelet Traits In The Nhlbi Trans-Omics For Precision Medicine Initiative, Amarise Little, Yao Hu, Quan Sun, Deepti Jain, Jai G. Broome, Ming-Huei Chen, Florian Thibord, Caitlin Mchugh, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing from NHLBI's Trans-Omics for Precision Medicine Initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet …

Defining The Genotypic And Phenotypic Spectrum Of X-Linked Msl3-Related Disorder, Theresa Brunet, Kirsty Mcwalter, Katharina Mayerhanser, Grace M Anbouba, Amy Armstrong-Javors, Ingrid Bader, Evan Baugh, Amber Begtrup, Caleb P Bupp, Bert L Callewaert, Anna Cereda, Margot A Cousin, Juan C Del Rey Jimenez, Laurie Demmer, Nikita R Dsouza, Nicole Fleischer, Ralitza H Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W Klee, Emily Lancaster, Kristin Lindstrom, Johannes A Mayr, Meriel Mcentagart, Naomi J L Meeks, Dana Mittag, Harrison Moore, Anne K Olsen, Damara Ortiz, Gretchen Parsons, Loren D M Pena, Richard E Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, Maria J Guillen Sacoto, G Bradley Schaefer, Rhonda E Schnur, Tiana M Scott, Daryl A Scott, Carolyn R Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Fossøy Stadheim, Jennifer A Sullivan, Jana Švantnerová, Lea Velsher, David S Wargowski, Ingrid M Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Paediatrics Publications

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of …

Concordance Between Antibiotic Resistance Genes By Multiplex Polymerase Chain Reaction And Antibiotic Susceptibility By Pooled Antibiotic Sensitivity Testing In Symptomatic Patients With Urinary Tract Infection, Annah Vollstedt, Dakun Wang, Natalie Luke, David Baunoch, Kirk J. Wojno, Kevin Cline, Natalie Gaines, Howard Korman, S Mohammad Jafri, David Wenzler, Frank Burks, Larry Sirls

Conference Presentation Abstracts

Introduction: Studies have shown many genes influence antibiotic resistance, and the relationship between genotypic and phenotypic antibiotic resistance is unclear. We sought to analyze the concordance between the presence of antibiotic resistance (ABR) genes and antibiotic susceptibility results in urine samples collected from symptomatic UTI patients. Methods: Urine samples were collected from patients presenting with possible UTI to 37 geographically disparate Urology clinics from July 2018 to February 2019. Multiplex polymerase chain reaction (M-PCR) was used to test for 33 different ABR genes. Samples in which at least one organism was identified at a quantity of ≥104 cells per mL, …

Concordance Between Antibiotic Resistance Genes By Multiplex Polymerase Chain Reaction And Antibiotic Susceptibility By Pooled Antibiotic Sensitivity Testing In Symptomatic Patients With Urinary Tract Infection, Annah Vollstedt, Dakun Wang, Natalie Luke, David Baunoch, Kirk J Wojno, Kevin Cline, Natalie Gaines, Howard Korman, S Mohammad Jafri, David Wenzler, Frank Burks, Larry Sirls

Conference Presentation Abstracts

Introduction: Studies have shown many genes influence antibiotic resistance, and the relationship between genotypic and phenotypic antibiotic resistance is unclear. We sought to analyze the concordance between the presence of antibiotic resistance (ABR) genes and antibiotic susceptibility results in urine samples collected from symptomatic UTI patients. Methods: Urine samples were collected from patients presenting with possible UTI to 37 geographically disparate Urology clinics from July 2018 to February 2019. Multiplex polymerase chain reaction (M-PCR) was used to test for 33 different ABR genes. Samples in which at least one organism was identified at a quantity of ≥104 cells per mL, …

Predicting Associations Of Mirnas And Candidate Gastric Cancer Genes For Nanomedicine, Aigul Akimniyazova, Anna Pyrkova, Vladimir N. Uversky, Anatoliy Ivashchenko

Molecular Medicine Faculty Publications

Nanoscale miRNAs regulate the synthesis of most human proteins involved in differentiation, proliferation, cell cycle, apoptosis, and other processes associated with the growth and the development of an organism. miRNAs also play a number of important roles in the development of gastric cancer. In this work, we studied the quantitative characteristics of miRNA interactions with 69 candidate gastric cancer genes using bioinformatics approaches. To this end, the MirTarget program was used, which determines the characteristics of miRNA binding to mRNA in the 5′UTR, CDS, and 3′UTR. Associations of miRNAs with alternative target genes and associations of genes with alternative miRNAs …

Association Of Genetic Variances In Adrb1 And Ppargc1a With Two-Kilometre Running Time-Trial Performance In Australian Football League Players: A Preliminary Study, Ysabel Jacob, Ryan S. Anderton, Jodie L. Cochrane Wilkie, Brent Rogalski, Simon M. Laws, Anthony Jones, Tania Spiteri, Nicolas H. Hart

Research outputs 2014 to 2021

Abstract: Genetic variants in the angiotensin-converting enzyme (ACE) (rs4343), alpha-actinin-3 (ACTN3) (rs1815739), adrenoceptor-beta-1 (ADRB1) (rs1801253), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) (rs8192678) genes have previously been associated with elite athletic performance. This study assessed the influence of polymorphisms in these candidate genes towards endurance test performance in 46 players from a single Australian Football League (AFL) team. Each player provided saliva buccal swab samples for DNA analysis and genotyping and were required to perform two independent two-kilometre running time-trials, six weeks apart. Linear mixed models were created to account for repeated measures over time and to determine whether …

Prd-2 Directly Regulates Casein Kinase I And Counteracts Nonsense-Mediated Decay In The Neurospora Circadian Clock., Christina M Kelliher, Randy Lambreghts, Qijun Xiang, Christopher L. Baker, Jennifer J Loros, Jay C Dunlap

Faculty Research 2020

No abstract provided.

A Novel Sting1 Variant Causes A Recessive Form Of Sting-Associated Vasculopathy With Onset In Infancy (Savi)., Bin Lin, Roberta Berard, Abdulrahman Al Rasheed, Buthaina Aladba, Philip J Kranzusch, Maggie Henderlight, Alexi Grom, Dana Kahle, Sofia Torreggiani, Alexander G Aue, Jacob Mitchell, Adriana A De Jesus, Grant S Schulert, Raphaela Goldbach-Mansky

Paediatrics Publications

No abstract provided.

Gene Selection For Optimal Prediction Of Cell Position In Tissues From Single-Cell Transcriptomics Data., Jovan Tanevski, Thin Nguyen, Buu Truong, Nikos Karaiskos, Mehmet Eren Ahsen, Xinyu Zhang, Chang Shu, Ke Xu, Xiaoyu Liang, Ying Hu, Hoang Vv Pham, Li Xiaomei, Thuc D Le, Adi L Tarca, Gaurav Bhatti, Roberto Romero, Nestoras Karathanasis, Phillipe Loher, Yang Chen, Zhengqing Ouyang, Disheng Mao, Yuping Zhang, Maryam Zand, Jianhua Ruan, Christoph Hafemeister, Peng Qiu, Duc Tran, Tin Nguyen, Attila Gabor, Thomas Yu, Justin Guinney, Enrico Glaab, Roland Krause, Peter Banda, Gustavo Stolovitzky, Nikolaus Rajewsky, Julio Saez-Rodriguez, Pablo Meyer

Computational Medicine Center Faculty Papers

Single-cell RNA-sequencing (scRNAseq) technologies are rapidly evolving. Although very informative, in standard scRNAseq experiments, the spatial organization of the cells in the tissue of origin is lost. Conversely, spatial RNA-seq technologies designed to maintain cell localization have limited throughput and gene coverage. Mapping scRNAseq to genes with spatial information increases coverage while providing spatial location. However, methods to perform such mapping have not yet been benchmarked. To fill this gap, we organized the DREAM Single-Cell Transcriptomics challenge focused on the spatial reconstruction of cells from the Drosophila embryo from scRNAseq data, leveraging as silver standard, genes with in situ hybridization …

Isolation And Identification Of Extended Spectrum Β-Lactamases (Esbls) Escherichia Colifrom Minced Camel Meat In Eastern Province, Saudi Arabia, Waleed Rizk El-Ghareeb, Sherief M. Abdel-Raheem, Theeb M. Al-Marri, Fanan A. Alaql, Mahmoud M. Fayez

The Thai Journal of Veterinary Medicine

Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. The aim of this study was to determine the rate of extended-spectrum β-lactamases (ESBL)-producing E. coliisolation from minced camel meat and identify the phenotype and genotype of the ESBL. A total of 150 samples were collected randomly from butchers’ shops in Al-Ahsa, Saudi Arabia. The results indicated that, overall, 17 (11.3 %) E. coliisolates were recovered from the minced meat samples. The isolates were classified biochemically at the species level using the VITEK 2 system. The antibiotic susceptibility of E. …

Updated Genes, Lifestyles, And Their Interactions For Human Longevity, Brenda Bin Su, Alexis Villafranca, Chunxiang Mao, Stephanie Hernandez, Stephanie Lozano, Masoud M. Zarei, Kesheng Wang, Saraswathy Nair, Chun Xu

Health & Biomedical Sciences Faculty Publications and Presentations

Healthy aging is the prolonging of optimal wellbeing during the progressive decline in physiological functions that are necessary for survival. Two important components of aging include an individual’s genetic makeup and lifestyle choices such as diet and exercise. Genetic factors are responsible for the functional physiology of the body including cell maintenance, metabolism and apoptosis. The individual effects of genes and lifestyle choices on aging are reported mainly in Caucasian populations, with very limited studies in minority populations. In this review, we included the effects of genes and environment and the interaction between them on aging in Hispanic population in …

Different Genetic Mechanisms Mediate Spontaneous Versus Uvr-Induced Malignant Melanoma, Blake Ferguson, Herlina Y. Handoko, Pamela Mukhopadhyay, Arash Chitsazan, Lois Balmer, Grant Morahan, Graeme J. Walker

Research outputs 2014 to 2021

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. …

Introducing The First Whole Genomes Of Nationals From The United Arab Emirates, Habiba S. Alsafar, Mariam Al-Ali, Gihan Daw Elbait, Mustafa H. Al-Maini, Dymitr Ruta, Braulio Peramo, Andreas Henschel, Guan K. Tay

Research outputs 2014 to 2021

Whole Genome Sequencing (WGS) provides an in depth description of genome variation. In the era of large-scale population genome projects, the assembly of ethnic-specific genomes combined with mapping human reference genomes of underrepresented populations has improved the understanding of human diversity and disease associations. In this study, for the first time, whole genome sequences of two nationals of the United Arab Emirates (UAE) at >27X coverage are reported. The two Emirati individuals were predominantly of Central/South Asian ancestry. An in-house customized pipeline using BWA, Picard followed by the GATK tools to map the raw data from whole genome sequences of …

Genetic Influence On Scar Height And Pliability After Burn Injury In Individuals Of European Ancestry: A Prospective Cohort Study, Hilary J. Wallace, Gemma Cadby, Phillip E. Melton, Fiona M. Wood, Sian Falder, Margaret M. Crowe, Lisa J. Martin, Karen Marlow, Sarah V. Ward, Mark W. Fear

Medical Papers and Journal Articles

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium^® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic …

The Role Of Ifih1 Gene Rs1990760 And Rs2111485 Single-Nucleotide Polymorphisms In Generalized Vitiligo Predisposition, Duru Onan, Ahu Yorulmaz, Fati̇h Süheyl Ezgü, Kadi̇r Mutlu Hayran, Seray Külcü Çakmak, Refi̇ka Ferda Artüz, Başak Yalçin

Turkish Journal of Medical Sciences

Interferon-induced helicase (IFIH1) is a gene locus that has been recently defined as a candidate for susceptibility to generalized vitiligo (GV). The objectives of this study were to assess the association of IFIH1 gene, rs2111485, and rs1990760 single-nucleotide polymorphisms (SNP) with susceptibility to GV and the autoimmune diseases accompanying GV.Materials and methods: We prospectively studied GV patients and frequency-matched healthy controls by age and sex. The genotypes of the participants were determined for rs1990760 and rs2111485 SNPs of IFIH1. Dominant, recessive, and additive models were evaluated for each SNP adjusted for age and sex. Results: The patients and their controls …

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …