Medicine and Health Sciences Commons^™

Tannic Acid Induces Endoplasmic Reticulum Stress-Mediated Apoptosis In Prostate Cancer, Prashanth K.B. Nagesh, Elham Hatami, Pallabita Chowdhury, Vivek Kumar Kashyap, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

Endoplasmic reticulum (ER) stress is an intriguing target with significant clinical importance in chemotherapy. Interference with ER functions can lead to the accumulation of unfolded proteins, as detected by transmembrane sensors that instigate the unfolded protein response (UPR). Therefore, controlling induced UPR via ER stress with natural compounds could be a novel therapeutic strategy for the management of prostate cancer. Tannic acid (a naturally occurring polyphenol) was used to examine the ER stress mediated UPR pathway in prostate cancer cells. Tannic acid treatment inhibited the growth, clonogenic, invasive, and migratory potential of prostate cancer cells. Tannic acid demonstrated activation of …

Optic Neuropathy And Congenital Glaucoma Associated With Probable Zika Virus Infection In Venezuelan Patients, C Gustavo De Moraes, Michele Petitto, Juan B. Yepez, Anavaj Sakuntabhai, Etienne Simon-Loriere, Mussaret B. Zaidi, Matthieu Prot, Claude Ruffie, Susan S. Kim, Gladys E. Maestre

School of Medicine Publications

Introduction: Although the current Zika virus (ZIKV) epidemic is a major public health concern, most reports have focused on congenital ZIKV syndrome, its most devastating manifestation. Severe ocular complications associated with ZIKV infections and possible pathogenetic factors are rarely described. Here, we describe three Venezuelan patients who developed severe ocular manifestations following ZIKV infections. We also analyse their serological response to ZIKV and dengue virus (DENV).

Case presentation: One adult with bilateral optic neuritis, a child of 4 years of age with retrobulbar neuritis [corrected]. and a newborn with bilateral congenital glaucoma had a recent history of an acute exanthematous …

Deficits In Visual Working-Memory Capacity And General Cognition In African Americans With Psychosis, Samuel R. Mathias, Emma E. Knowles, Jennifer Barrett, Tamara Beetham, Olivia Leach, Sebastiano Buccheri, Katrina Aberizk, John Blangero, Russell A. Poldrack, David C. Glahn

School of Medicine Publications

On average, patients with psychosis perform worse than controls on visual change-detection tasks, implying that psychosis is associated with reduced capacity of visual working memory (WM). In the present study, 79 patients diagnosed with various psychotic disorders and 166 controls, all African Americans, completed a change-detection task and several other neurocognitive measures. The aims of the study were to (1) determine whether we could observe a between-group difference in performance on the change-detection task in this sample; (2) establish whether such a difference could be specifically attributed to reduced WM capacity (k); and (3) estimate k in the …

Verbal Memory Performance And Reduced Cortical Thickness Of Brain Regions Along The Uncinate Fasciculus In Young Adult Cannabis Users, Nina Levar, Alan N. Francis, Matthew J. Smith, Wilson C. Ho, Jodi M. Gilman

School of Medicine Publications

Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory. This study investigated the impact of cannabis use on UF structures and its association with memory performance in young …

Family History And Obesity In Youth, Their Effect On Acylcarnitine/Aminoacids Metabolomics And Non-Alcoholic Fatty Liver Disease (Nafld). Structural Equation Modeling Approach, Maria Elena Romero-Ibarguengoitia, Felipe Vadillo-Ortega, Augusto Enrique Caballero, Isabel Ibarra-Gonzalez, Arturo Herrera-Rosas, Maria Fabiola Serratos-Canales, Mireya Leon-Hernandez, Antonio Gonzalez-Chavez, Srinivas Mummidi, Ravindranath Duggirala, Juan Carlos Lopez Alvarenga

School of Medicine Publications

Background

Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher …

Protein Kinase D1 Regulates Subcellular Localisation And Metastatic Function Of Metastasis-Associated Protein 1, Aditya Ganju, Subhash C. Chauhan, Bilal B. Hafeez, Kyle Doxtater, Manish Tripathi, Nadeem Zafar, Murali M. Yallapu, Rakesh Kumar, Meena Jaggi

School of Medicine Publications

Background: Cancer progression and metastasis is profoundly influenced by protein kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other pathways. However, the nature of regulatory relationship between the PKD1 and MTA1, and its resulting impact on cancer metastasis remains unknown. Here we present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1.

Methods: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were determined using western blotting and reverse-transcription quantitative real-time PCR. Immunoprecipitation and proximity ligation assay (PLA) were used to determine the interaction between PKD1 and MTA1. PKD1-mediated nucleo-cytoplasmic export and polyubiquitin-dependent proteosomal …

Genetic And Environmental (Physical Fitness And Sedentary Activity) Interaction Effects On Cardiometabolic Risk Factors In Mexican American Children And Adolescents, Rector Arya, Vidya S. Farook, Roy G. Resendez, Srinivas Mummidi, Laura Almasy, Joanne E. Curran, Christopher P. Jenkinson, John Blangero, Ravindranath Duggirala, Vincent P. Diego

School of Medicine Publications

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited. The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6–17 years). The environments examined were sedentary activity (SA), assessed by recalls from “yesterday” (SAy) and “usually” (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment—insulin resistance (HOMA‐IR), high‐density lipoprotein cholesterol …

Incidence Of Dementia In Elderly Latin Americans: Results Of The Maracaibo Aging Study, Gladys E. Maestre, Luis J. Mena, Jesus D. Melgarejo, Daniel C. Aguirre-Acevedo, Gloria Pino-Ramírez, Milady Urribarrí, Inara J. Chacon, Carlos A. Chavez, Luis Falque-Madrid, Ciro A. Gaona

School of Medicine Publications

Introduction—There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study (MAS) to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans.

Methods—The DSM IV-R was used to diagnose dementia, which was classified as Alzheimer’s disease (AD), vascular dementia (VaD), or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years of follow-up (p-y).

Results—The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% CI 7.13–11.44; 8026 total p-y), 5.18 for AD (95% CI 3.72–7.03; …

Diet-Induced Early-Stage Atherosclerosis In Baboons: Lipoproteins, Atherogenesis, And Arterial Compliance, Michael Mahaney, Genesio M. Karere, David L. Rainwater, Venkata Saroja Voruganti, Edward J. Dick Jr, Michael Owston, Karen S. Rice, Laura Cox, Anthony G. Comuzzie, John L. Vandeberg

School of Medicine Publications

Background

The purpose of this study was to determine if dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized nonhuman primate model.

Methods

We fed 112 baboons a high cholesterol, high fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy.

Results

We observed evidence of atherosclerosis in all but one baboon fed the two-year challenge diet. CVD risk biomarkers, …

International Consensus Statement On Allergy And Rhinology: Allergic Rhinitis, Sarah K. Wise, Sandra Y. Lin, Elina Toskala, Richard R. Orlandi, Cezmi A. Akdis, Jeremiah A. Alt, Antoine Azar, Fuad M. Baroody, Claus Bachert, Helene J. Krouse

School of Medicine Publications

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document.

Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus …

Additive Genetic Variation In The Craniofacial Skeleton Of Baboons (Genus Papio) And Its Relationship To Body And Cranial Size, Jessica L. Joganic, Katherine E. Willmore, Joan T. Richtsmeier, Kenneth M. Weiss, Michael Mahaney, Jeffrey Rogers, James M. Cheverud

School of Medicine Publications

Objectives

Determining the genetic architecture of quantitative traits and genetic correlations among them is important for understanding morphological evolution patterns. We address two questions regarding papionin evolution: (1) what effect do body and cranial size, age, and sex have on phenotypic (VP) and additive genetic (VA) variation in baboon crania, and (2) how might additive genetic correlations between craniofacial traits and body mass affect morphological evolution?

Materials and Methods

We use a large captive pedigreed baboon sample to estimate quantitative genetic parameters for craniofacial dimensions (EIDs). Our models include nested combinations of the covariates listed above. We also simulate the …

Data On Genetic Associations Of Carotid Atherosclerosis Markers In Mexican American And European American Rheumatoid Arthritis Subjects, Rector Arya, Agustin Escalante, Vidya S. Farook, Jose F. Restrepo, Daniel F. Battafarano, Marcio Almeida, Mark Kos, Marcel Fourcaudot, Srinivas Mummidi, Satish Kumar, Joanne E. Curran, Christopher Jenkinson, John Blangero, Ravi Duggirala, Inmaculada Del Rincon

School of Medicine Publications

Carotid Intima-media thickness (CIMT) and plaque are well established markers of subclinical atherosclerosis and are widely used for identifying subclinical atherosclerotic disease. We performed association analyses using Metabochip array to identify genetic variants that influence variation in CIMT and plaque, measured using B-mode ultrasonography, in rheumatoid arthritis (RA) patients. Data on genetic associations of common variants associated with both CIMT and plaque in RA subjects involving Mexican Americans (MA) and European Americans (EA) populations are presented in this article. Strong associations were observed after adjusting for covariate effects including baseline clinical characteristics and statin use. Susceptibility loci and genes and/or …

Joint Analysis Of Cortical Area And Thickness As A Replacement For The Analysis Of The Volume Of The Cerebral Cortex, Anderson M. Winkler, Douglas N. Greve, Knut J. Bjuland, Thomas E. Nichols, Mert R. Sabuncu, Asta K. Håberg, Jon Skranes, Lars M. Rimol

School of Medicine Publications

Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on …

Neurodegenerative Disease Biomarkers Aβ1–40, Aβ1–42, Tau, And P-Tau181 In The Vervet Monkey Cerebrospinal Fluid: Relation To Normal Aging, Genetic Influences, And Cerebral Amyloid Angiopathy, Jason A. Chen, Scott C. Fears, Anna J. Jasinska, Alden Huang, Noor B. Al-Sharif, Kevin E. Scheibel, Thomas D. Dyer, Anne M. Fagan, John Blangero, M. J. Jorgensen, J. R. Kaplan, N. B. Freimer, Giovanni Coppol

School of Medicine Publications

Background: The Caribbean vervet monkey (Chlorocebus aethiops sabaeus) is a potentially valuable animal model of neurodegenerative disease. However, the trajectory of aging in vervets and its relationship to human disease is incompletely understood.

Methods: To characterize biomarkers associated with neurodegeneration, we measured cerebrospinal fluid (CSF) concentrations of Aβ1-40, Aβ1-42, total tau, and p-tau181 in 329 members of a multigenerational pedigree. Linkage and genome-wide association were used to elucidate a genetic contribution to these traits.

Results: Aβ1-40 concentrations were significantly correlated with age, brain total surface area, and gray matter thickness. Levels of p-tau181 were associated with cerebral volume …

Radiation Therapy In Metastatic Neuroblastoma, Meenu Gupta, Anupam Dhasmana

School of Medicine Publications

Neuroblastoma is the commonest extracranial solid tumor in children, and metastasis at presentation is seen in more than 50% of cases. The role of radiotherapy as a palliative modality in patients with advanced neuroblastoma provides better symptomatic relief. Palliative radiotherapy dose schedules can be given either in single hypofractionation from 4 to 8 Gy or fractionated radiotherapy that can range from 21 to 30.6 Gy. Doseresponse relationship trend has been reported in the palliative setting of bone metastasis. Because of the proximity of tumor to critical organs, serious adverse effects can be avoided with conformal techniques. Although currently there is …

Development Of Polyvinylpyrrolidone/Paclitaxel Self-Assemblies For Breast Cancer, Pallabita Chowdhury, Prashanth K.B. Nagesh, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu

School of Medicine Publications

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an …

Elucidation The Toxicity Mechanism Of Zinc Oxide Nanoparticle Using Molecular Docking Approach With Proteins, Krishna Pal Singh, Anupam Dhasmana, Qamar Rahman

School of Medicine Publications

Objective: At present, toxicological tests are resource-intensive, time-consuming and require a large pool of animal models for toxicity assessment. To speed up the toxicity evaluation and to reduce animal suffering during toxicity assessment, the use of alternative methods including computational models is in high demand. The computational toxicity prediction methods are very helpful for the regulatory bodies to quickly assess the health impact of nanomaterial materials. In the present work, we have examined the mechanism of zinc oxide nanoparticle (ZnO-NP)-proteins interaction and their effect of surface chemistries of ZnO-NP on the bioactive conformation of chemokines and other cytological proteins using …

Deep Coverage Whole Genome Sequences And Plasma Lipoprotein(A) In Individuals Of European And African Ancestries, Seyedeh M. Zekavat, Sanni Ruotsalainen, Robert E. Handsaker, Maris Alver, Jonathan Bloom, Timothy Poterba, Laura Almasy, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Juan M. Peralta, Harald H. H. Goring

School of Medicine Publications

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding …

Study Of Anaemia In Children And Current Update, Sanjeev Kumar Shukla, Shubhra Shukla, Rajesh Kumar Verma, Lakshya Veer Singh, Bashah J. Khan, Vikas Gupta, D. P. Saxena, Shahaj Uddin Ahmed, Anupam Dhasmana, Naveen Sharma

School of Medicine Publications

Anaemia in children is a major public health problem throughout the biosphere. It is estimated that at least one-third of the populace has been at one-time anemic. It is often multifactorial, iron deficiency being the most frequent etiology and reasons like malaria endemicity, poor nutrition including micronutrient deficiency, haemoglobinopathies, frequent bacterial infections and high parasitic infestations have been given for these high prevalence rates. Chronic Anaemia may impair growth, cardiac function and cognitive development in infants but other consequences are rather poorly explored more thoroughly. Chronic disorders and iron deficiency were the most common causes of Anaemia. Anaemia was frequently …

In Silico Cd4+, Cd8+ & Humoral Immunity Associated Antigenic Epitope Prediction And Hla Distribution Analysis Of Htlv-I, Tasneem Bano, Essam Mohammed Janahi, Anupam Dhasmana, Mohtashim Lohani, Shafiul Haque, Raju K. Mandel, Sajad A. Dar, Arshad Jawed, Mohd Wahid, Naseem Akhter, Mohammaed Y. Areeshi

School of Medicine Publications

Purpose: The linkage of human T-cell leukemia virus type 1 (HTLV-1) to fatal diseases is a well known fact for many years. However, there has been no significant progress in the field of the treatment that can lead to the development of a successful vaccine. Furthermore, there are no means of assessing the risk of disease and its prognosis in the infected people.

Methods:The current study has taken the cognizance of the importance of host’s immune response in reducing the risk of infectious diseases to carry out immunoinformatics driven epitope screening strategy of vaccine candidates against HTLV-1. In this …

Contribution Of Inbred Singletons To Variance Component Estimation Of Heritability And Linkage, Lucy Blondell, August N. Blackburn, Mark Kos, John Blangero, Harald Hh Goring

School of Medicine Publications

Objectives:

An interesting consequence of consanguinity is that the inbred singleton becomes informative for genetic variance. We determine the contribution of an inbred singleton to variance component analysis of heritability and linkage.

Methods:

Statistical theory for the power of variance component analysis of quantitative traits is used to determine the expected contribution of an inbred singleton to likelihood-ratio tests of heritability and linkage.

Results:

In variance component models an inbred singleton contributes relatively little to a test of heritability, but can contribute substantively to a test of linkage. For small to moderate QTL effects and a level of inbreeding comparable …

Heritability Estimates On Resting State Fmri Data Using Enigma Analysis Pipeline, Bhim M. Adhikari, Neda Jahanshad, Dinesh Shukla, David C. Glahn, John Blangero, Richard C. Reynolds, Robert W. Cox, Els Fieremans

School of Medicine Publications

Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analysis consortium (ENIGMA), combine data collected by independent studies worldwide to achieve more generalizable estimates of effect sizes and more reliable and reproducible outcomes. Such efforts require harmonized image analyses protocols to extract phenotypes consistently. This harmonization is particularly challenging for resting state fMRI due to the wide variability of acquisition protocols and scanner platforms; this leads to site-to-site variance in quality, resolution and temporal signal-to-noise ratio (tSNR). An effective harmonization should provide optimal measures for data of different qualities. We developed a multi-site rsfMRI analysis pipeline to allow research …

Endovascular Thrombectomy For Mild Strokes: How Low Should We Go? A Multicenter Cohort Study, Amrou Sarraj, Ameer E. Hassan, Sean I. Savitz, James C. Grotta, Chunyan Cai, Kaushik N. Parsha, Christine M. Farrell, Bita Imam, Clark W. Sitton, Sujan T. Reddy

School of Medicine Publications

Background and Purpose:Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS

Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSSoutcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location.

Results: 214 patients (EVT-124, medical management-90) were …

Non-Congenital Severe Ocular Complications Of Zika Virus Infection, Mussaret B. Zaidi, C Gustavo De Moraes, Michele Petitto, Juan B. Yepez, Anavaj Sakuntabhai, Etienne Simon-Loriere, Matthieu Prot, Claude Ruffie, Susan S. Kim, Gladys E. Maestre

School of Medicine Publications

In 2016, during a major Zika virus (ZIKV) outbreak in Maracaibo, Venezuela, a 49-year-old woman and an unrelated 4-year-old boy developed bilateral optic neuritis 2–3 weeks after presenting an acute febrile illness characterized by low-grade fever, rash and myalgia [1]. Both patients presented sudden, painless bilateral loss of vision with no corneal or uveal abnormalities. Fundoscopic examination revealed oedema of the optic nerve and optic disc pallor. Optical coherence tomography confirmed bilateral optic nerve head swelling in the case of the adult, but it was not carried out in the child. Automated perimetry performed in the adult revealed bilateral diffuse …

Kaposi Sarcoma Incidence In Females Is Nearly Four-Fold Higher In The Lower Rio Grande Valley Compared To The Texas Average, Wendy Innis-Whitehouse, Xiaohui Wang, Nicolas Restrepo, Carlos Salas, Katia Moreno, Alvaro Restrepo, Megan Keniry

School of Medicine Publications

The Lower Rio Grande Valley (LRGV) is located on U.S.-Mexican border with a population that is 90% Hispanic[1]. Comprised of Hidalgo, Cameron, Starr and Willacy counties, this region has the highest poverty rate and one of the highest incidences of Type 2 diabetes in the United States[2],[3],[4]. Previous studies demonstrated a high prevalence of Human Herpes Virus 8 (HHV8) in the LRGV[5],[6],[7]. HHV8 infection has been causally linked to Kaposi Sarcoma (KS)[8]. Here, we retrospectively examine the incidence of KS in the LRGV in a set of HIV-negative Hispanic patients. Strikingly, the incidence of KS was higher in LRGV women …

Sequence Data And Association Statistics From 12,940 Type 2 Diabetes Cases And Controls, Jason Flannick, Christian Fuchsberger, Anubha Mahajan, Tanya M. Teslovich, Vineeta Agarwala, Kyle J. Gaulton, Lizz Caulkins, Rector Arya, Ravi Duggirala, Joanne E. Curran, Satish Kumar, John Blangero

School of Medicine Publications

To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1–5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency …

Impact Of The G84e Variant On Hoxb13 Gene And Protein Expression In Formalin-Fixed, Paraffin-Embedded Prostate Tumours, Liesel M. Fitzgerald, Kelsie Raspin, James R. Marthick, Matt A. Field, Roslyn C. Malley, Russell J. Thomson, Nicholas B. Blackburn, Erika Banks, Annette Banks, Jac C. Charlesworth, Shaun Donovan, Joanne L. Dickinson

School of Medicine Publications

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type …

Sex-Biased Microrna Expression In Mammals And Birds Reveals Underlying Regulatory Mechanisms And A Role In Dosage Compensation, Maria Warnefors, Katharina Mössinger, Jean Halbert, Anja Studer, Tania Studer, John L. Vandeberg, Isa Lindgren, Amir Fallahshahroudi, Per Jensen, Henrik Kaessmann

School of Medicine Publications

Sexual dimorphism depends on sex-biased gene expression, but the contributions of microRNAs (miRNAs) have not been globally assessed. We therefore produced an extensive small RNA sequencing data set to analyze male and female miRNA expression profiles in mouse, opossum, and chicken. Our analyses uncovered numerous cases of somatic sex-biased miRNA expression, with the largest proportion found in the mouse heart and liver. Sex-biased expression is explained by miRNA-specific regulation, including sex-biased chromatin accessibility at promoters, rather than piggybacking of intronic miRNAs on sex-biased protein-coding genes. In mouse, but not opossum and chicken, sex bias is coordinated across tissues such that …

Tc-Ptp Nuclear Trafficking In Keratinocytes, Mihwa Kim, Liza D. Morales, Dae Joon Kim

School of Medicine Publications

No abstract provided.

Identity-By-Descent Mapping Identifies Major Locus For Serum Triglycerides In Amerindians Largely Explained By An Apoc3 Founder Mutation, Wen-Chi Hsueh, Anup K. Nair, Sayuko Kobes, Peng Chen, Harald H. H. Goring, Toni I. Pollin, Alka Malhotra, William C. Knowler, Leslie J. Baier, Robert L. Hanson

School of Medicine Publications

Background—Identity-by-descent (IBD) mapping using empirical estimates of IBD allele sharing may be useful for studies of complex traits in founder populations, where hidden relationships may augment the inherent genetic information that can be used for localization.

Methods and Results—Through IBD mapping, using ~400,000 SNPs, of serum lipid profiles we identified a major linkage signal for triglycerides (TG) in 1,007 Pima Indians (LOD=9.23, p=3.5×10−11 on chromosome 11q). In subsequent fine-mapping and replication association studies in ~7,500 Amerindians, we determined that this signal reflects effects of a loss-of-function Ala43Thr substitution in APOC3 (rs147210663) and 3 established functional SNPs in APOA5. …