DOCSLIB.ORG

Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences The atalogue for ransmission enetics in rabs C T G A CTGA Database A-Kinase Anchor Protein 6 Alternative Names cardiac and skeletal muscle and several regions of AKAP6 the brain. A-Kinase Anchor Protein, 100-KD AKAP100 Epidemiology in the Arab World Saudi Arabia Record Category Monies et al. (2017) described the genomic Gene locus landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a WHO-ICD 3-year-old female from a consanguineous family, N/A to gene loci presented with intellectual disability and precocious puberty. Reflex WES helped identify a novel Incidence per 100,000 Live Births heterozygous mutation (c.1874A>T, p.Y625F) in N/A to gene loci exon 4 of the patient’s AKAP6 gene, which was predicted to be deleterious. Through an internal OMIM Number matchmaking effort, the authors identified another 604691 patient with intellectual disability with a de-novo truncating variant (c.1572_1573del, Mode of Inheritance p.Lys525Glufs30*) in AKAP6. These two findings N/A to gene loci help suggest the possibility of AKAP6 being a bona-fide disease gene for intellectual disability in Gene Map Locus humans. 14q12 References Description Monies D, Abouelhoda M, AlSayed M, Alhassnan The AKAP6 gene encodes a protein belonging to Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, the A-Kinase Anchor Proteins (AKAPs) family. Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Members of this family are responsible for binding Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes to the regulatory subunit of the holoenzyme Protein B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, Kinase A (PKA) and anchoring it to the nuclear Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al membrane or sarcoplasmic reticulum. AKAP6 is Saud BK, Kurdi W, Makhseed N, Alqasim T, El responsible for maintaining a cAMP-responsive Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, signaling complex consisting of PKA, PDE4D3 and Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, EPAC1. Through this complex, the AKAP6 protein Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, coordinates two coupled cAMP dependent loops. Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout The protein is also believed to play a role in the R, Dabbagh O, Shagrani M, Broering D, Tulbah M, positive regulation of cell growth, particularly in Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, cardiac muscle cell development. Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Molecular Genetics Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, The AKAP6 gene is located on the long arm of Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, chromosome 14. It spans a length of 508.4 kb of Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh DNA and its coding sequence is contained within H, AlGhonaium A, Alkharfy TM, Al Mutairi F, 20 exons. The gene encodes a 256.7 kDa protein Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani product comprising 2319 amino acids. An FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, additional 120 kDa isoform of the AKAP6 protein Alenizi AS, Hussein MH, Hassan S, Khalil M, exists due to an alternatively spliced transcript Tabarki B, Alshahwan S, Oshi A, Sabr Y, variant. The gene is found to be overexpressed in Alsaadoun S, Salih MA, Mohamed S, Sultana H, Copyright © Centre for Arab Genomic Studies 1 Tamim A, El-Haj M, Alshahrani S, Bubshait DK, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, External Links Shah Z, Moghrabi N, Meyer BF, Alkuraya FS. The http://www.genecards.org/cgi- landscape of genetic diseases in Saudi Arabia based bin/carddisp.pl?gene=AKAP6 on the first 1000 diagnostic panels and exomes. Hum Genet. 2017 Aug;136(8):921-939. PMID: Contributors 28600779. Sayeeda Hana 03.08.2017 Related CTGA Records Copyright © Centre for Arab Genomic Studies 2 .
Load more

Recommended publications
  • Hearing Aging Is 14.1±0.4% GWAS-Heritable
    medRxiv preprint doi: https://doi.org/10.1101/2021.07.05.21260048; this version posted July 7, 2021. 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. It is made available under a CC-BY-NC 4.0 International license . Predicting age from hearing test results with machine learning reveals the genetic and environmental factors underlying accelerated auditory aging Alan Le Goallec1,2+, Samuel Diai1+, Théo Vincent1, Chirag J. Patel1* 1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA 2Department of Systems, Synthetic and Quantitative Biology, Harvard University, Cambridge, MA, 02118, USA +Co-first authors *Corresponding author Contact information: Chirag J Patel [email protected] Abstract With the aging of the world population, age-related hearing loss (presbycusis) and other hearing disorders such as tinnitus become more prevalent, leading to reduced quality of life and social isolation. Unveiling the genetic and environmental factors leading to age-related auditory disorders could suggest lifestyle and therapeutic interventions to slow auditory aging. In the following, we built the first machine learning-based hearing age predictor by training models to predict chronological age from hearing test results (root mean squared error=7.10±0.07 years; R-Squared=31.4±0.8%). We defined hearing age as the prediction outputted by the model on unseen samples, and accelerated auditory aging as the difference between a participant’s hearing age and age. We then performed a genome wide association study [GWAS] and found that accelerated hearing aging is 14.1±0.4% GWAS-heritable.
    [Show full text]
  • 1 Supporting Information for a Microrna Network Regulates
    Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia.
    [Show full text]
  • Physiological and Pathophysiological Regulation of the Ryanodine Receptor in Skeletal Muscle
    Physiological and pathophysiological regulation of the ryanodine receptor in skeletal muscle Alisa Umanskaya Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2015 © 2015 Alisa Umanskaya All rights reserved Abstract Physiological and pathophysiological regulation of ryanodine receptor in skeletal muscle Alisa Umanskaya Ryanodine receptor calcium release channels are essential for skeletal muscle contraction, as they mediate the release of calcium ions from intracellular stores into the cytosol. The data presented in this dissertation demonstrate the evolutionarily conserved mechanisms of skeletal muscle ryanodine receptor regulation in the physiological and pathophysiological states. Adrenergic stimulation causes increased skeletal muscle force, however, despite the well- established role of this physiological response, the molecular mechanism is not known. Here we present a mechanism whereby phosphorylation of a single amino acid on the ryanodine receptor is a key signal in the physiological stress-induced inotropic response in mouse skeletal muscle. Therefore acute post-translational modifications of ryanodine receptor channels are important for healthy muscle contraction. Conversely, chronic stress-induced post-translational modifications result in poorly functioning murine ryanodine receptor channels that contribute to skeletal muscle dysfunction in age- dependent skeletal muscle weakness and Muscular Dystrophies. Finally, we present data that demonstrates striking evolutionary conservation in ryanodine receptor regulation in the physiological and pathophysiological states between mice and C. elegans. This work has broad implications for understanding the underlying mechanisms of skeletal muscle contraction and important disorders that affect human health. Furthermore, this works presents ryanodine receptor channels as a viable therapeutic target for age-related skeletal muscle weakness, Muscular Dystrophies, and also implicates C.
    [Show full text]
  • Myogenin Controls Via AKAP6 Non-Centrosomal Microtubule
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.11.421263; this version posted December 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Myogenin controls via AKAP6 non-centrosomal microtubule 2 organizing center formation at the nuclear envelope 3 4 Robert Becker1, Silvia Vergarajauregui1, Florian Billing1, Maria Sharkova1, 5 Eleonora Lippolis2, Kamel Mamchaoui3, Fulvia Ferrazzi2,4,5,6, Felix B. Engel1,6,* 6 7 1Experimental Renal and Cardiovascular Research, Department of Nephropathology, 8 Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 9 91054 Erlangen, Germany 10 2Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 11 91054 Erlangen, Germany 12 3Sorbonne Universités UPMC Université Paris 06, INSERM U974, CNRS FRE3617, 13 Center for Research in Myology, GH Pitié Salpêtrière, 47 Boulevard de l’Hôpital, 75013 14 Paris, France 15 4Department of Nephropathology, Institute of Pathology, Friedrich-Alexander- 16 Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany 17 5Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 18 91054 Erlangen, Germany 19 6Muscle Research Center Erlangen (MURCE), 91054 Erlangen, Germany 20 21 Short title: Myogenin controls ncMTOC formation 22 23 *Corresponding author: 24 Felix B. Engel, Universitätsklinikum Erlangen, Schwabachanlage 12 (TRC), 91054 25 Erlangen, Germany, [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.11.421263; this version posted December 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
    [Show full text]
  • A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans
    Journal of Personalized Medicine Article A Genome-Wide Association Study of Idiopathic Dilated Cardiomyopathy in African Americans Huichun Xu 1,* ID , Gerald W. Dorn II 2, Amol Shetty 3, Ankita Parihar 1, Tushar Dave 1, Shawn W. Robinson 4, Stephen S. Gottlieb 4 ID , Mark P. Donahue 5, Gordon F. Tomaselli 6, William E. Kraus 5,7 ID , Braxton D. Mitchell 1,8 and Stephen B. Liggett 9,* 1 Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; [email protected] (A.P.); [email protected] (T.D.); [email protected] (B.D.M.) 2 Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; [email protected] 3 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA; [email protected] 4 Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; [email protected] (S.W.R.); [email protected] (S.S.G.) 5 Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27708, USA; [email protected] (M.P.D.); [email protected] (W.E.K.) 6 Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD 21218, USA; [email protected] 7 Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA 8 Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration
    [Show full text]
  • Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
    Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo
    [Show full text]
  • Combinatorial Strategies Using CRISPR/Cas9 for Gene Mutagenesis in Adult Mice
    Combinatorial strategies using CRISPR/Cas9 for gene mutagenesis in adult mice Avery C. Hunker A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2019 Reading Committee: Larry S. Zweifel, Chair Sheri J. Mizumori G. Stanley McKnight Program Authorized to Offer Degree: Pharmacology 2 © Copyright 2019 Avery C. Hunker 3 University of Washington ABSTRACT Combinatorial strategies using CRISPR/Cas9 for gene mutagenesis in adult mice Avery C. Hunker Chair of the Supervisory Committee: Larry Zweifel Department of Pharmacology A major challenge to understanding how genes modulate complex behaviors is the inability to restrict genetic manipulations to defined cell populations or circuits. To circumvent this, we created a simple strategy for limiting gene knockout to specific cell populations using a viral-mediated, conditional CRISPR/SaCas9 system in combination with intersectional genetic strategies. A small single guide RNA (sgRNA) directs Staphylococcus aureus CRISPR-associated protein (SaCas9) to unique sites on DNA in a Cre-dependent manner resulting in double strand breaks and gene mutagenesis in vivo. To validate this technique we targeted nine different genes of diverse function in distinct cell types in mice and performed an array of analyses to confirm gene mutagenesis and subsequent protein loss, including IHC, cell-type specific DNA sequencing, electrophysiology, Western blots, and behavior. We show that these vectors are as efficient as conventional conditional gene knockout and provide a viable alternative to complex genetic crosses. This strategy provides additional benefits of 4 targeting gene mutagenesis to cell types previously difficult to isolate, and the ability to target genes in specific neural projections for gene inactivation.
    [Show full text]
  • Genome-Wide Characterization of Genetic Variants and Putative
    Boschiero et al. BMC Genomics (2018) 19:83 DOI 10.1186/s12864-018-4444-0 RESEARCH ARTICLE Open Access Genome-wide characterization of genetic variants and putative regions under selection in meat and egg-type chicken lines Clarissa Boschiero1,4* , Gabriel Costa Monteiro Moreira1,AlmasAraGheyas2, Thaís Fernanda Godoy1, Gustavo Gasparin1, Pilar Drummond Sampaio Corrêa Mariani1,MarcelaPaduan1, Aline Silva Mello Cesar1, Mônica Corrêa Ledur3 and Luiz Lehmann Coutinho1 Abstract Background: Meat and egg-type chickens have been selected for several generations for different traits. Artificial and natural selection for different phenotypes can change frequency of genetic variants, leaving particular genomic footprints throghtout the genome. Thus, the aims of this study were to sequence 28 chickens from two Brazilian lines (meat and white egg-type) and use this information to characterize genome-wide genetic variations, identify putative regions under selection using Fst method, and find putative pathways under selection. Results: A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more variants detected from the broiler (meat-type) line. Although most were located in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512 stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter protein functions. Genes harboring intolerant non-synonymous SNPs affected metabolic pathways related mainly to reproduction and endocrine systems in the white-egg layer line, and lipid metabolism and metabolic diseases in the broiler line. Fst analysis in sliding windows, using SNPs and INDELs separately, identified over 300 putative regions of selection overlapping with more than 250 genes. For the first time in chicken, INDEL variants were considered for selection signature analysis, showing high level of correlation in results between SNP and INDEL data.
    [Show full text]
  • Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer
    University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-5-2018 Functional Signature Ontology-Based Identification and alidationV of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer Beth Neilsen University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Bioinformatics Commons, Cancer Biology Commons, and the Oncology Commons Recommended Citation Neilsen, Beth, "Functional Signature Ontology-Based Identification and alidationV of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer" (2018). Theses & Dissertations. 268. https://digitalcommons.unmc.edu/etd/268 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer By Beth K. Neilsen A DISSERTATION Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Cancer Research Graduate Program Under the Supervision of Professor Robert E. Lewis University of Nebraska Medical Center Omaha, Nebraska May 2018 Supervisory Committee: Jennifer Black, Ph.D. Jing (Jenny) Wang, Ph.D. Allison Cushman-Vokoun, M.D./Ph.D. Juan Cui, Ph.D. ii To my parents, Dr. and Mrs. Mitchell and Rebecca Neilsen, For always encouraging me to think critically, pushing me to be the best version of me, for giving me the space to think for myself, teaching me compassion, and most importantly, for molding me into the person I am today.
    [Show full text]
  • GWAS Meta-Analysis Reveals Novel Loci and Genetic Correlates for General Cognitive Function: a Report from the COGENT Consortium
    OPEN Molecular Psychiatry (2017) 22, 336–345 www.nature.com/mp IMMEDIATE COMMUNICATION GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium JW Trampush1,56, MLZ Yang2,56,JYu1,3, E Knowles4, G Davies5,6, DC Liewald6, JM Starr5,7, S Djurovic8,9, I Melle9,10, K Sundet10,11, A Christoforou9,12, I Reinvang11, P DeRosse1,3, AJ Lundervold13, VM Steen9,12, T Espeseth10,11, K Räikkönen14, E Widen15, A Palotie15,16,17, JG Eriksson18,19,20,21, I Giegling22, B Konte22, P Roussos23,24,25, S Giakoumaki26, KE Burdick23,25, A Payton27,28, W Ollier29, M Horan30, O Chiba-Falek31, DK Attix31,32, AC Need33, ET Cirulli34, AN Voineskos35, NC Stefanis36,37,38, D Avramopoulos39,40, A Hatzimanolis36,37,38, DE Arking40, N Smyrnis36,37, RM Bilder41, NA Freimer41, TD Cannon42, E London41, RA Poldrack43, FW Sabb44, E Congdon41, ED Conley45, MA Scult46, D Dickinson47, RE Straub48, G Donohoe49, D Morris50, A Corvin50, M Gill50, AR Hariri46, DR Weinberger48, N Pendleton29,30, P Bitsios51, D Rujescu22, J Lahti14,52, S Le Hellard9,12, MC Keller53, OA Andreassen9,10,54, IJ Deary5,6, DC Glahn4, AK Malhotra1,3,55 and T Lencz1,3,55 The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾ 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT).
    [Show full text]
  • Systematic Identification and Quantification of Substrate Specificity Determinants in Human Protein Kinases
    Systematic identification and quantification of substrate specificity determinants in human protein kinases (Identificación y cuantificación sistemática de determinantes de la especificidad por sustrato en las proteínas quinasas de humano) Manuel Alejandro Alonso Tarajano ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB.
    [Show full text]
  • Hypoxia As an Evolutionary Force
    “The genetic architecture of adaptations to high altitude in Ethiopia” Gorka Alkorta-Aranburu1, Cynthia M. Beall2*, David B. Witonsky1, Amha Gebremedhin3, Jonathan K. Pritchard1,4, Anna Di Rienzo1* 1 Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America, 2 Department of Anthropology, Case Western Research University, Cleveland, Ohio, United States of America, 3 Department of Internal Medicine, Faculty of Medicine, Addis Ababa University, Addis Ababa, Ethiopia, 4 Howard Hughes Medical Institute * E-mail: [email protected] and [email protected] Corresponding authors: Anna Di Rienzo Department of Human Genetics University of Chicago 920 E. 58th Street Chicago, IL 60637, USA. Cynthia M. Beall Anthropology Department Case Western Reserve University 238 Mather Memorial Building 11220 Bellflower Road Cleveland, OH 44106, USA. 1 ABSTRACT Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome- wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians.
    [Show full text]