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Autism Multiplex Family with 16P11.2P12.2 Microduplication Syndrome in Monozygotic Twins and Distal 16P11.2 Deletion in Their Brother
European Journal of Human Genetics (2012) 20, 540–546 & 2012 Macmillan Publishers Limited All rights reserved 1018-4813/12 www.nature.com/ejhg ARTICLE Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother Anne-Claude Tabet1,2,3,4, Marion Pilorge2,3,4, Richard Delorme5,6,Fre´de´rique Amsellem5,6, Jean-Marc Pinard7, Marion Leboyer6,8,9, Alain Verloes10, Brigitte Benzacken1,11,12 and Catalina Betancur*,2,3,4 The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5–30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5–30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28–30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40–29.25 Mb), inherited from his apparently healthy father. -
(12) United States Patent (10) Patent No.: US 9,605,041 B2 Greengard Et Al
USOO9605041B2 (12) United States Patent (10) Patent No.: US 9,605,041 B2 Greengard et al. (45) Date of Patent: Mar. 28, 2017 (54) REGULATORY PROTEINS AND INHIBITORS 5,385,915 A 1/1995 Buxbaum et al. 5,393,755 A 2f1995 NeuStadt et al. 5,521, 184 A 5/1996 Zimmermann (75) Inventors: Paul Greengard, New York, NY (US); 5,543,520 A 8/1996 Zimmermann Wenjie Luo, New York, NY (US); Gen 5,719,283 A 2f1998 Bell et al. He, New York, NY (US); Peng Li, 5,733,914 A 3/1998 Blankley et al. New York, NY (US); Lawrence 5,744,346 A 4/1998 Chrysler et al. Wennogle, New York, NY (US) 5,777, 195 A 7/1998 Fienberg et al. 5,824,683 A 10, 1998 McKittrick et al. 5,849,770 A 12/1998 Head et al. (73) Assignees: INTRA-CELLULAR THERAPIES, 5,885,834 A 3/1999 Epstein INC., New York, NY (US): THE 5,939,419 A 8, 1999 Tulshian et al. ROCKEFELLER UNIVERSITY, 5,962,492 A 10, 1999 Warrellow New York, NY (US) 6,013,621 A 1/2000 Nishi et al. 6,107.301 A 8, 2000 Aldrich et al. 6,133,273 A 10/2000 Gilbert et al. (*) Notice: Subject to any disclaimer, the term of this 6,147,073. A 11/2000 Battistini et al. patent is extended or adjusted under 35 6,235,742 B1 5, 2001 Bell et al. U.S.C. 154(b) by 974 days. 6,235,746 B1 5, 2001 Davis et al. -
Mutation Analysis of Genes Within the Dynactin Complex in a Cohort of Hereditary Peripheral Neuropathies
Clin Genet 2016: 90: 127–133 © 2015 John Wiley & Sons A/S. Printed in Singapore. All rights reserved Published by John Wiley & Sons Ltd CLINICAL GENETICS doi: 10.1111/cge.12712 Original Article Mutation analysis of genes within the dynactin complex in a cohort of hereditary peripheral neuropathies a a Tey S., Ahmad-Annuar A., Drew A.P., Shahrizaila N., Nicholson G.A., S. Tey , A. Ahmad-Annuar , Kennerson M.L. Mutation analysis of genes within the dynactin complex in A.P. Drewb, N. Shahrizailac, , a cohort of hereditary peripheral neuropathies. G.A. Nicholsonb d and Clin Genet 2016: 90: 127–133. © John Wiley & Sons A/S. Published by M.L. Kennersonb,d John Wiley & Sons Ltd, 2015 aDepartment of Biomedical Science, The cytoplasmic dynein–dynactin genes are attractive candidates for Faculty of Medicine, University of Malaya, b neurodegenerative disorders given their functional role in retrograde Kuala Lumpur, Malaysia, Northcott transport along neurons. The cytoplasmic dynein heavy chain (DYNC1H1) Neuroscience Laboratory, ANZAC Research Institute, and Sydney Medical gene has been implicated in various neurodegenerative disorders, and School, University of Sydney, Sydney, dynactin 1 (DCTN1) genes have been implicated in a wide spectrum of Australia, cDepartment of Medicine, disorders including motor neuron disease, Parkinson’s disease, spinobulbar Faculty of Medicine, University of Malaya, muscular atrophy and hereditary spastic paraplegia. However, the Kuala Lumpur, Malaysia, and dMolecular involvement of other dynactin genes with inherited peripheral neuropathies Medicine Laboratory, Concord Hospital, (IPN) namely, hereditary sensory neuropathy, hereditary motor neuropathy Sydney, Australia and Charcot–Marie–Tooth disease is under reported. We screened eight genes; DCTN1-6 and ACTR1A and ACTR1B in 136 IPN patients using Key words: Charcot–Marie–Tooth – whole-exome sequencing and high-resolution melt (HRM) analysis. -
Fine Mapping and Expression of Candidate Genes Within the Chromosome 10 QTL Region of the High and Low Alcohol Drinking Rats
View metadata, citation and similar papers at core.ac.uk brought to you by CORE HHS Public Access provided by IUPUIScholarWorks Author manuscript Author ManuscriptAuthor Manuscript Author Alcohol Manuscript Author . Author manuscript; Manuscript Author available in PMC 2017 July 18. Published in final edited form as: Alcohol. 2010 September ; 44(6): 477–485. doi:10.1016/j.alcohol.2010.06.004. Fine mapping and expression of candidate genes within the Chromosome 10 QTL region of the High and Low Alcohol Drinking Rats Paula J. Bice1, Tiebing Liang1, Lili Zhang1, Tamara J. Graves1, Lucinda G. Carr1, Dongbing Lai2, Mark W. Kimpel3, and Tatiana Foroud2 1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA 2Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA 3Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA Abstract The high and low alcohol-drinking (HAD and LAD) rats were selectively bred for differences in alcohol intake. The HAD/LAD rats originated from the N/Nih heterogeneous stock (HS) developed from intercrossing 8 inbred rat strains. The HAD × LAD F2 were genotyped, and a powerful analytical approach, utilizing ancestral recombination as well as F2 recombination, was used to narrow a QTL for alcohol drinking to a 2 cM region on distal chromosome 10 that was in common in the HAD1/LAD1 and HAD2/LAD2 analyses. Quantitative real time PCR (qRT-PCR) was used to examine mRNA expression of 6 candidate genes (Crebbp, Trap1, Gnptg, Clcn7, Fahd1, and Mapk8ip3) located within the narrowed QTL region in the HAD1/LAD1 rats. -
35Th International Society for Animal Genetics Conference 7
35th INTERNATIONAL SOCIETY FOR ANIMAL GENETICS CONFERENCE 7. 23.16 – 7.27. 2016 Salt Lake City, Utah ABSTRACT BOOK https://www.asas.org/meetings/isag2016 INVITED SPEAKERS S0100 – S0124 https://www.asas.org/meetings/isag2016 epigenetic modifications, such as DNA methylation, and measuring different proteins and cellular metab- INVITED SPEAKERS: FUNCTIONAL olites. These advancements provide unprecedented ANNOTATION OF ANIMAL opportunities to uncover the genetic architecture GENOMES (FAANG) ASAS-ISAG underlying phenotypic variation. In this context, the JOINT SYMPOSIUM main challenge is to decipher the flow of biological information that lies between the genotypes and phe- notypes under study. In other words, the new challenge S0100 Important lessons from complex genomes. is to integrate multiple sources of molecular infor- T. R. Gingeras* (Cold Spring Harbor Laboratory, mation (i.e., multiple layers of omics data to reveal Functional Genomics, Cold Spring Harbor, NY) the causal biological networks that underlie complex traits). It is important to note that knowledge regarding The ~3 billion base pairs of the human DNA rep- causal relationships among genes and phenotypes can resent a storage devise encoding information for be used to predict the behavior of complex systems, as hundreds of thousands of processes that can go on well as optimize management practices and selection within and outside a human cell. This information is strategies. Here, we describe a multi-step procedure revealed in the RNAs that are composed of 12 billion for inferring causal gene-phenotype networks underly- nucleotides, considering the strandedness and allelic ing complex phenotypes integrating multi-omics data. content of each of the diploid copies of the genome. -
Supplementary Information – Postema Et Al., the Genetics of Situs Inversus Totalis Without Primary Ciliary Dyskinesia
1 Supplementary information – Postema et al., The genetics of situs inversus totalis without primary ciliary dyskinesia Table of Contents: Supplementary Methods 2 Supplementary Results 5 Supplementary References 6 Supplementary Tables and Figures Table S1. Subject characteristics 9 Table S2. Inbreeding coefficients per subject 10 Figure S1. Multidimensional scaling to capture overall genomic diversity 11 among the 30 study samples Table S3. Significantly enriched gene-sets under a recessive mutation model 12 Table S4. Broader list of candidate genes, and the sources that led to their 13 inclusion Table S5. Potential recessive and X-linked mutations in the unsolved cases 15 Table S6. Potential mutations in the unsolved cases, dominant model 22 2 1.0 Supplementary Methods 1.1 Participants Fifteen people with radiologically documented SIT, including nine without PCD and six with Kartagener syndrome, and 15 healthy controls matched for age, sex, education and handedness, were recruited from Ghent University Hospital and Middelheim Hospital Antwerp. Details about the recruitment and selection procedure have been described elsewhere (1). Briefly, among the 15 people with radiologically documented SIT, those who had symptoms reminiscent of PCD, or who were formally diagnosed with PCD according to their medical record, were categorized as having Kartagener syndrome. Those who had no reported symptoms or formal diagnosis of PCD were assigned to the non-PCD SIT group. Handedness was assessed using the Edinburgh Handedness Inventory (EHI) (2). Tables 1 and S1 give overviews of the participants and their characteristics. Note that one non-PCD SIT subject reported being forced to switch from left- to right-handedness in childhood, in which case five out of nine of the non-PCD SIT cases are naturally left-handed (Table 1, Table S1). -
Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis a Virus Replication
International Journal of Molecular Sciences Article Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication Tatsuo Kanda 1,* , Reina Sasaki-Tanaka 1, Ryota Masuzaki 1 , Naoki Matsumoto 1, Hiroaki Okamoto 2 and Mitsuhiko Moriyama 1 1 Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan; [email protected] (R.S.-T.); [email protected] (R.M.); [email protected] (N.M.); [email protected] (M.M.) 2 Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-3-3972-8111 Abstract: Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) Citation: Kanda, T.; Sasaki-Tanaka, and its triggering of interferon-β production. -
Leveraging Omics Data to Expand the Value and Understanding of Alternative Splicing
Leveraging Omics Data to Expand the Value and Understanding of Alternative Splicing By ______________________ Nathan T. Johnson A Dissertation Submitted to the Faculty of WORCESTER POLYTECHNIC INSTITUTE In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy In Bioinformatics & Computational Biology APPROVED: __________________________ __________________________ Dmitry Korkin, Ph.D. Amity L. Manning, Ph.D. Advisor Committee Member Program Director __________________________ __________________________ Zheyang Wu, Ph.D. Scarlet Shell, Ph.D. Committee Member Committee Member __________________________ Ben Raphael, Ph.D. External Committee Member i “Science, my boy, is made up of mistakes, but they are mistakes which it is useful to make, because they lead little by little to the truth.” Jules Verne, Journey to the Center of the Earth ii ABSTRACT Utilizing ‘omics’ data of diverse types such as genomics, proteomics, transcriptomics, epigenomics, and others has largely been attributed as holding great promise for solving the complexity of many health and ecological problems such as complex genetic diseases and parasitic destruction of farming crops. By using bioinformatics, it is possible to take advantage of ‘omics’ data to gain a systems level molecular perspective to achieve insight into possible solutions. One possible solution is understanding and expanding the use of alternative splicing (AS) of mRNA precursors. Typically, genes are considered the focal point as the main players in the molecular world. However, due to recent ‘omics’ analysis across the past decade, AS has been demonstrated to be the main player in causing protein diversity. This is possible as AS rearranges the key components of a gene (exon, intron, and untranslated regions) to generate diverse functionally unique proteins and regulatory RNAs. -
Wo 2010/065567 A2
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 10 June 2010 (10.06.2010) WO 2010/065567 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/889 (2006.01) A61K 31/16 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 36/736 (2006.01) A61K 31/05 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/166 (2006.01) A61P 5/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/US2009/066294 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 1 December 2009 (01 .12.2009) NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (25) Filing Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/1 18,945 1 December 2008 (01 .12.2008) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, (71) Applicant (for all designated States except US): LIFES¬ TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, PAN EXTENSION LLC [US/US]; 933 First Colonial ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Road, Suite 114, Virginia Beach, VA 23454 (US). -
Identification and Functional Characterisation of Oncogenic Pathway Signatures in Malignant Lymphoma
Identification and functional characterisation of oncogenic pathway signatures in malignant Lymphoma Doctoral Thesis In partial fulfilment of the requirements for the degree “Doctor rerum naturalium (Dr. rer. nat.)” in the Molecular Medicine Study Program at the Georg-August University Göttingen Graduate School 1034 submitted by Alexandra Schrader born in Soest Göttingen, 2011 Thesis Committee Prof Dr. Dieter Kube (Supervisor) E-Mail [email protected] Phone 0049-551-391537 Postal Address Universitätsmedizin Göttingen Zentrum Innere Medizin Abteilung Hämatologie und Onkologie Robert-Koch-Straße 40 37075 Göttingen Prof Dr. Heidi Hahn E-Mail [email protected] Phone 0049-551-39-14010 Postal Address Universitätsmedizin Göttingen Zentrum Hygiene und Humangenetik Institut für Humangenetik Heinrich-Düker-Weg 12 37073 Göttingen Prof Dr. Martin Oppermann E-Mail [email protected] Phone 0049-551-395822 Postal Address Universitätsmedizin Göttingen Zentrum Hygiene und Humangenetik Abteilung Zelluläre und Molekulare Immunologie Humboldtallee 34 37073 Göttingen Date of Disputation: 22.09.2011 Affidavit By this I declare that I independently authored the presented thesis: “Identification and functional characterisation of oncogenic pathway signatures in malignant Lymphoma” and that I did not use other auxiliary means than indicated. Paragraphs that are taken from other publications, by wording or by sense, are marked in every case with a specification of the literary source. Furthermore I declare that I carried out the scientific experiments following -
Content Based Search in Gene Expression Databases and a Meta-Analysis of Host Responses to Infection
Content Based Search in Gene Expression Databases and a Meta-analysis of Host Responses to Infection A Thesis Submitted to the Faculty of Drexel University by Francis X. Bell in partial fulfillment of the requirements for the degree of Doctor of Philosophy November 2015 c Copyright 2015 Francis X. Bell. All Rights Reserved. ii Acknowledgments I would like to acknowledge and thank my advisor, Dr. Ahmet Sacan. Without his advice, support, and patience I would not have been able to accomplish all that I have. I would also like to thank my committee members and the Biomed Faculty that have guided me. I would like to give a special thanks for the members of the bioinformatics lab, in particular the members of the Sacan lab: Rehman Qureshi, Daisy Heng Yang, April Chunyu Zhao, and Yiqian Zhou. Thank you for creating a pleasant and friendly environment in the lab. I give the members of my family my sincerest gratitude for all that they have done for me. I cannot begin to repay my parents for their sacrifices. I am eternally grateful for everything they have done. The support of my sisters and their encouragement gave me the strength to persevere to the end. iii Table of Contents LIST OF TABLES.......................................................................... vii LIST OF FIGURES ........................................................................ xiv ABSTRACT ................................................................................ xvii 1. A BRIEF INTRODUCTION TO GENE EXPRESSION............................. 1 1.1 Central Dogma of Molecular Biology........................................... 1 1.1.1 Basic Transfers .......................................................... 1 1.1.2 Uncommon Transfers ................................................... 3 1.2 Gene Expression ................................................................. 4 1.2.1 Estimating Gene Expression ............................................ 4 1.2.2 DNA Microarrays ...................................................... -
MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
ARTICLE OPEN ACCESS MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor Andreea Ilinca, MD, PhD, Elisabet Englund, MD, PhD, Sofie Samuelsson, MSc, Katarina Truv´e, PhD, Correspondence Efthymia Kafantari, MSc, MSc, Nicolas Martinez-Majander, MD, Jukka Putaala, MD, PhD, Claes Håkansson, MD, Dr. Ilinca [email protected] Arne G. Lindgren, MD, PhD,* and Andreas Puschmann, MD, PhD* Neurol Genet 2021;7:e548. doi:10.1212/NXG.0000000000000548 Abstract Objective To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. Methods We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole- genome sequencing (WGS) and intrafamilial cosegregation analyses. Results Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family.