Transcriptome Analysis of Recurrently Deregulated Genes Across Multiple
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Cytogenomic SNP Microarray - Fetal ARUP Test Code 2002366 Maternal Contamination Study Fetal Spec Fetal Cells
Patient Report |FINAL Client: Example Client ABC123 Patient: Patient, Example 123 Test Drive Salt Lake City, UT 84108 DOB 2/13/1987 UNITED STATES Gender: Female Patient Identifiers: 01234567890ABCD, 012345 Physician: Doctor, Example Visit Number (FIN): 01234567890ABCD Collection Date: 00/00/0000 00:00 Cytogenomic SNP Microarray - Fetal ARUP test code 2002366 Maternal Contamination Study Fetal Spec Fetal Cells Single fetal genotype present; no maternal cells present. Fetal and maternal samples were tested using STR markers to rule out maternal cell contamination. This result has been reviewed and approved by Maternal Specimen Yes Cytogenomic SNP Microarray - Fetal Abnormal * (Ref Interval: Normal) Test Performed: Cytogenomic SNP Microarray- Fetal (ARRAY FE) Specimen Type: Direct (uncultured) villi Indication for Testing: Patient with 46,XX,t(4;13)(p16.3;q12) (Quest: EN935475D) ----------------------------------------------------------------- ----- RESULT SUMMARY Abnormal Microarray Result (Male) Unbalanced Translocation Involving Chromosomes 4 and 13 Classification: Pathogenic 4p Terminal Deletion (Wolf-Hirschhorn syndrome) Copy number change: 4p16.3p16.2 loss Size: 5.1 Mb 13q Proximal Region Deletion Copy number change: 13q11q12.12 loss Size: 6.1 Mb ----------------------------------------------------------------- ----- RESULT DESCRIPTION This analysis showed a terminal deletion (1 copy present) involving chromosome 4 within 4p16.3p16.2 and a proximal interstitial deletion (1 copy present) involving chromosome 13 within 13q11q12.12. This -
Mutational Landscape Differences Between Young-Onset and Older-Onset Breast Cancer Patients Nicole E
Mealey et al. BMC Cancer (2020) 20:212 https://doi.org/10.1186/s12885-020-6684-z RESEARCH ARTICLE Open Access Mutational landscape differences between young-onset and older-onset breast cancer patients Nicole E. Mealey1 , Dylan E. O’Sullivan2 , Joy Pader3 , Yibing Ruan3 , Edwin Wang4 , May Lynn Quan1,5,6 and Darren R. Brenner1,3,5* Abstract Background: The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours. Methods: In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages “deconstructSigs” and “SomaticSignatures” to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset. Results: Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young- onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young- onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. -
Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
Genetic and Bioinformatic Analyses of the Expression and Function of PI3K
Zhou et al. BMC Medical Genomics 2012, 5:34 http://www.biomedcentral.com/1755-8794/5/34 RESEARCH ARTICLE Open Access Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library Jin Zhou1, Geng Bo Chen3, Yew Chung Tang4, Rohit Anthony Sinha1, Yonghui Wu8, Chui Sun Yap1, Guihua Wang5, Junbo Hu5, Xianmin Xia5, Patrick Tan2,8,9,10, Liang Kee Goh3,6,7 and Paul Michael Yen1* Abstract Background: While there is strong evidence for phosphatidylinositol 3-kinase (PI3K) involvement in cancer development, there is limited information about the role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K regulatory subunit p55γ, is over-expressed in glioblastoma and ovarian cancers, but its expression in gastric cancer (GC) is not known. We thus used genetic and bioinformatic approaches to examine PIK3R3 expression and function in GC, the second leading cause of cancer mortality world-wide and highly prevalent among Asians. Methods: Primary GC and matched non-neoplastic mucosa tissue specimens from a unique Asian patient gastric cancer library were comprehensively profiled with platforms that measured genome-wide mRNA expression, DNA copy number variation, and DNA methylation status. Function of PIK3R3 was predicted by IPA pathway analysis of co-regulated genes with PIK3R3, and further investigated by siRNA knockdown studies. Cell proliferation was estimated by crystal violet dye elution and BrdU incorporation assay. Cell cycle distribution was analysed by FACS. Results: PIK3R3 was significantly up-regulated in GC specimens (n = 126, p < 0.05), and 9.5 to 15% tumors showed more than 2 fold increase compare to the paired mucosa tissues. -
Assessing the Non-Genetic and Genetic Factors Affecting Refraction in the Aging Adult Population
ASSESSING THE NON-GENETIC AND GENETIC FACTORS AFFECTING REFRACTION IN THE AGING ADULT POPULATION by Samantha Bomotti A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, MD January, 2018 ©2018 Samantha Bomotti All Rights Reserved Abstract Refractive errors are the most common form of visual impairment in the world, and are becoming an increasing public health burden as the world’s population ages. Refractive errors arise from changes in the shape of the eye, such as axial length and corneal curvature, or from aging of the lens. Refraction is a quantitative trait underlying refractive errors. The goal of this project was to investigate the non-genetic and genetic factors affecting refraction, a complex multifactorial trait, in the aging adult population. We used phenotypic data available from the population-based Beaver Dam Eye Study (BDES) consisting of 4,972 individuals aged 43-86 years at baseline to identify and characterize the association of nuclear sclerosis, among other factors, with refraction and changes in refraction. We then imputed exome array data in a subset of BDES participants to enhance our coverage of protein-coding regions and identify variants associated with refraction or either of its biological determinants, axial length and corneal curvature. Finally, we conducted a heritability analysis to determine whether the heritability of refraction varied by nuclear sclerosis severity, and to quantify the genetic or environmental influences shared between refraction and nuclear sclerosis. We determined nuclear cataract is the primary contributor to the myopic shift observed in older persons, as only those with nuclear cataract experienced a myopic shift while those without nuclear cataract did not. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
Lessons Learned from Additional Research Analyses of Unsolved Clinical Exome Cases Mohammad K
Eldomery et al. Genome Medicine (2017) 9:26 DOI 10.1186/s13073-017-0412-6 RESEARCH Open Access Lessons learned from additional research analyses of unsolved clinical exome cases Mohammad K. Eldomery1,18†, Zeynep Coban-Akdemir1†, Tamar Harel1†,JillA.Rosenfeld1, Tomasz Gambin1,2, Asbjørg Stray-Pedersen3, Sébastien Küry4,SandraMercier4,5,DavorLessel6,JonasDenecke7, Wojciech Wiszniewski1,8, Samantha Penney1, Pengfei Liu1,9,WeiminBi1,9, Seema R. Lalani1,8, Christian P. Schaaf1,8,10, Michael F. Wangler1,8, Carlos A. Bacino1,8, Richard Alan Lewis1,10, Lorraine Potocki1,8, Brett H. Graham1,8,JohnW.Belmont1,8, Fernando Scaglia1,8,JordanS.Orange11,12, Shalini N. Jhangiani13,TheodoreChiang13, Harsha Doddapaneni13, Jianhong Hu13, Donna M. Muzny13, Fan Xia1,9, Arthur L. Beaudet1,9,EricBoerwinkle13,14, Christine M. Eng1,9, Sharon E. Plon1,8,11,15,V.ReidSutton1,8, Richard A. Gibbs1,13,16, Jennifer E. Posey1, Yaping Yang1,9 and James R. Lupski1,8,11,13,17* Abstract Background: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. Methods: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent–offspring trios. -
Deciphering the Long Non-Coding Rnas and Micrornas Coregulation Networks in Ovarian Cancer Development: an Overview
cells Review Deciphering the Long Non-Coding RNAs and MicroRNAs Coregulation Networks in Ovarian Cancer Development: An Overview César López-Camarillo 1,2,* , Erika Ruíz-García 2,3 , Yarely M. Salinas-Vera 4 , Macrina B. Silva-Cázares 5 , Olga N. Hernández-de la Cruz 1, Laurence A. Marchat 6 and Dolores Gallardo-Rincón 2,3 1 Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, 03100 CDMX, Mexico; [email protected] 2 Grupo de Investigación en Cáncer de Ovario y Endometrio, Instituto Nacional de Cancerología, 14080 CDMX, Mexico; [email protected] (E.R.-G.); [email protected] (D.G.-R.) 3 Laboratorio de Medicina Traslacional y Departamento de Tumores Gastrointestinales, Instituto Nacional de Cancerología, 14080 CDMX, Mexico 4 Departamento de Bioquímica, CINVESTAV-IPN, 07360 CDMX, Mexico; [email protected] 5 Coordinación Académica Región Altiplano, Universidad Autónoma de San Luis Potosí, 78700 San Luis Potosí, Mexico; [email protected] 6 Programa en Biomedicina Molecular y Red de Biotecnología, Instituto Politécnico Nacional, 07340 CDMX, Mexico; [email protected] * Correspondence: [email protected] Abstract: Non-coding RNAs are emergent elements from the genome, which do not encode for proteins but have relevant cellular functions impacting almost all the physiological processes oc- Citation: López-Camarillo, C.; curring in eukaryotic cells. In particular, microRNAs and long non-coding RNAs (lncRNAs) are a Ruíz-García, E.; Salinas-Vera, Y.M.; new class of small RNAs transcribed from the genome, which modulate the expression of specific Silva-Cázares, M.B.; Hernández-de la Cruz, O.N.; Marchat, L.A.; genes at transcriptional and posttranscriptional levels, thus adding a new regulatory layer in the flux Gallardo-Rincón, D. -
Genomic Annotation of the Meningioma Tumor Suppressor Locus on Chromosome 1P34
Oncogene (2004) 23, 1014–1020 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $25.00 www.nature.com/onc Genomic annotation of the meningioma tumor suppressor locus on chromosome 1p34 Erik P Sulman1,2, Peter S White2,3 and Garrett M Brodeur*,2,3 1The Fels Institute for Molecular Biology and Cancer Research, Temple University School of Medicine, Philadelphia, PA 19140, USA; 2Division of Oncology, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; 3Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA Meningioma is a frequently occurring tumor of the 13–20% of adult brain tumors, with an overall incidence meninges surrounding the central nervous system. Loss of approximately 7–8/100 000 per year, including of the short arm of chromosome 1 (1p) is the second most asymptomatic cases discovered at autopsy (Nakasu frequent chromosomal abnormality observed in these et al., 1987; Bondy and Ligon, 1996). Although usually tumors. Previously,we identified a 3.7 megabase (Mb) benign, 5–10% of tumors are malignant and invasive region of consistent deletion on 1p33–p34 in a panel of 157 and 20–40% of patients suffer from recurrent disease tumors. Loss of this region was associated with advanced (Zu¨ lch, 1979; Mathiesen et al., 1996). Meningiomas are disease and predictive for tumor relapse. In this report,a also associated with Neurofibromatosis type 2, occur- high-resolution integrated map of the region was con- ring nearly as frequently in that disease as vestibular structed (CompView) to identify all markers in the schwannomas (Evans et al., 1992). -
A Systematic Genome-Wide Association Analysis for Inflammatory Bowel Diseases (IBD)
A systematic genome-wide association analysis for inflammatory bowel diseases (IBD) Dissertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftlichen Fakultät der Christian-Albrechts-Universität zu Kiel vorgelegt von Dipl.-Biol. ANDRE FRANKE Kiel, im September 2006 Referent: Prof. Dr. Dr. h.c. Thomas C.G. Bosch Koreferent: Prof. Dr. Stefan Schreiber Tag der mündlichen Prüfung: Zum Druck genehmigt: der Dekan “After great pain a formal feeling comes.” (Emily Dickinson) To my wife and family ii Table of contents Abbreviations, units, symbols, and acronyms . vi List of figures . xiii List of tables . .xv 1 Introduction . .1 1.1 Inflammatory bowel diseases, a complex disorder . 1 1.1.1 Pathogenesis and pathophysiology. .2 1.2 Genetics basis of inflammatory bowel diseases . 6 1.2.1 Genetic evidence from family and twin studies . .6 1.2.2 Single nucleotide polymorphisms (SNPs) . .7 1.2.3 Linkage studies . .8 1.2.4 Association studies . 10 1.2.5 Known susceptibility genes . 12 1.2.5.1 CARD15. .12 1.2.5.2 CARD4. .15 1.2.5.3 TNF-α . .15 1.2.5.4 5q31 haplotype . .16 1.2.5.5 DLG5 . .17 1.2.5.6 TNFSF15 . .18 1.2.5.7 HLA/MHC on chromosome 6 . .19 1.2.5.8 Other proposed IBD susceptibility genes . .20 1.2.6 Animal models. 21 1.3 Aims of this study . 23 2 Methods . .24 2.1 Laboratory information management system (LIMS) . 24 2.2 Recruitment. 25 2.3 Sample preparation. 27 2.3.1 DNA extraction from blood. 27 2.3.2 Plate design . -
A Genomic Analysis of Rat Proteases and Protease Inhibitors
A genomic analysis of rat proteases and protease inhibitors Xose S. Puente and Carlos López-Otín Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain Send correspondence to: Carlos López-Otín Departamento de Bioquímica y Biología Molecular Facultad de Medicina, Universidad de Oviedo 33006 Oviedo-SPAIN Tel. 34-985-104201; Fax: 34-985-103564 E-mail: [email protected] Proteases perform fundamental roles in multiple biological processes and are associated with a growing number of pathological conditions that involve abnormal or deficient functions of these enzymes. The availability of the rat genome sequence has opened the possibility to perform a global analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into five catalytic classes: 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. Overall, this distribution is similar to that of the mouse degradome, but significatively more complex than that corresponding to the human degradome composed of 561 proteases and homologs. This increased complexity of the rat protease complement mainly derives from the expansion of several gene families including placental cathepsins, testases, kallikreins and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in the rat and mouse genomes and may contribute to explain some functional differences between these two closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with the mouse protease inhibitor complement and the marked expansion of families of cysteine and serine protease inhibitors in rat and mouse with respect to human.