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Ciliopathiesneuromuscularciliopathies Disorders Disorders Ciliopathiesciliopathies
NeuromuscularCiliopathiesNeuromuscularCiliopathies Disorders Disorders CiliopathiesCiliopathies AboutAbout EGL EGL Genet Geneticsics EGLEGL Genetics Genetics specializes specializes in ingenetic genetic diagnostic diagnostic testing, testing, with with ne nearlyarly 50 50 years years of of clinical clinical experience experience and and board-certified board-certified labor laboratoryatory directorsdirectors and and genetic genetic counselors counselors reporting reporting out out cases. cases. EGL EGL Genet Geneticsics offers offers a combineda combined 1000 1000 molecular molecular genetics, genetics, biochemical biochemical genetics,genetics, and and cytogenetics cytogenetics tests tests under under one one roof roof and and custom custom test testinging for for all all medically medically relevant relevant genes, genes, for for domestic domestic andand international international clients. clients. EquallyEqually important important to to improving improving patient patient care care through through quality quality genetic genetic testing testing is is the the contribution contribution EGL EGL Genetics Genetics makes makes back back to to thethe scientific scientific and and medical medical communities. communities. EGL EGL Genetics Genetics is is one one of of only only a afew few clinical clinical diagnostic diagnostic laboratories laboratories to to openly openly share share data data withwith the the NCBI NCBI freely freely available available public public database database ClinVar ClinVar (>35,000 (>35,000 variants variants on on >1700 >1700 genes) genes) and and is isalso also the the only only laboratory laboratory with with a a frefree oen olinnlein dea dtabtaabsaes (eE m(EVmCVlaCslas)s,s f)e, afetuatruinrgin ag vaa vraiarniatn ctl acslasisfiscifiactiaotino sne saercahrc ahn adn rde rpeoprot rrte rqeuqeuset sint tinetrefarcfaec, ew, hwichhic fha cfailcitialiteatse rsa praidp id interactiveinteractive curation curation and and reporting reporting of of variants. -
Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice
Loyola University Chicago Loyola eCommons Biology: Faculty Publications and Other Works Faculty Publications 2013 Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice Mihaela Palicev Gunter P. Wagner James P. Noonan Benedikt Hallgrimsson James M. Cheverud Loyola University Chicago, [email protected] Follow this and additional works at: https://ecommons.luc.edu/biology_facpubs Part of the Biology Commons Recommended Citation Palicev, M, GP Wagner, JP Noonan, B Hallgrimsson, and JM Cheverud. "Genomic Correlates of Relationship QTL Involved in Fore- Versus Hind Limb Divergence in Mice." Genome Biology and Evolution 5(10), 2013. This Article is brought to you for free and open access by the Faculty Publications at Loyola eCommons. It has been accepted for inclusion in Biology: Faculty Publications and Other Works by an authorized administrator of Loyola eCommons. For more information, please contact [email protected]. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. © Palicev et al., 2013. GBE Genomic Correlates of Relationship QTL Involved in Fore- versus Hind Limb Divergence in Mice Mihaela Pavlicev1,2,*, Gu¨ nter P. Wagner3, James P. Noonan4, Benedikt Hallgrı´msson5,and James M. Cheverud6 1Konrad Lorenz Institute for Evolution and Cognition Research, Altenberg, Austria 2Department of Pediatrics, Cincinnati Children‘s Hospital Medical Center, Cincinnati, Ohio 3Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University 4Department of Genetics, Yale University School of Medicine 5Department of Cell Biology and Anatomy, The McCaig Institute for Bone and Joint Health and the Alberta Children’s Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada 6Department of Anatomy and Neurobiology, Washington University *Corresponding author: E-mail: [email protected]. -
Synergistic Genetic Interactions Between Pkhd1 and Pkd1 Result in an ARPKD-Like Phenotype in Murine Models
BASIC RESEARCH www.jasn.org Synergistic Genetic Interactions between Pkhd1 and Pkd1 Result in an ARPKD-Like Phenotype in Murine Models Rory J. Olson,1 Katharina Hopp ,2 Harrison Wells,3 Jessica M. Smith,3 Jessica Furtado,1,4 Megan M. Constans,3 Diana L. Escobar,3 Aron M. Geurts,5 Vicente E. Torres,3 and Peter C. Harris 1,3 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background Autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct, with ADPKD usually caused by the genes PKD1 or PKD2 (encoding polycystin-1 and polycystin-2, respectively) and ARPKD caused by PKHD1 (encoding fibrocys- tin/polyductin [FPC]). Primary cilia have been considered central to PKD pathogenesis due to protein localization and common cystic phenotypes in syndromic ciliopathies, but their relevance is questioned in the simple PKDs. ARPKD’s mild phenotype in murine models versus in humans has hampered investi- gating its pathogenesis. Methods To study the interaction between Pkhd1 and Pkd1, including dosage effects on the phenotype, we generated digenic mouse and rat models and characterized and compared digenic, monogenic, and wild-type phenotypes. Results The genetic interaction was synergistic in both species, with digenic animals exhibiting pheno- types of rapidly progressive PKD and early lethality resembling classic ARPKD. Genetic interaction be- tween Pkhd1 and Pkd1 depended on dosage in the digenic murine models, with no significant enhancement of the monogenic phenotype until a threshold of reduced expression at the second locus was breached. -
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. -
Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in A
Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in a novel member of the chromodomain gene family cause CHARGE syndrome. L.E.L.M. Vissers1, C.M.A. van Ravenswaaij1, R. Admiraal2, J.A. Hurst3, B.B.A. de Vries1, I.M. Janssen1, W.A. van der Vliet1, E.H.L.P.G. Huys1, P.J. de Jong4, B.C.J. Hamel1, E.F.P.M. Schoenmakers1, H.G. Brunner1, A. Geurts van Kessel1, J.A. Veltman1. 1) Dept Human Genetics, UMC Nijmegen, Nijmegen, Netherlands; 2) Dept Otorhinolaryngology, UMC Nijmegen, Nijmegen, Netherlands; 3) Dept Clinical Genetics, The Churchill Hospital, Oxford, United Kingdom; 4) Children's Hospital Oakland Research Institute, BACPAC Resources, Oakland, CA. CHARGE association denotes the non-random occurrence of ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies and deafness (OMIM #214800). Almost all patients with CHARGE association are sporadic and its cause was unknown. We and others hypothesized that CHARGE association is due to a genomic microdeletion or to a mutation in a gene affecting early embryonic development. In this study array- based comparative genomic hybridization (array CGH) was used to screen patients with CHARGE association for submicroscopic DNA copy number alterations. De novo overlapping microdeletions in 8q12 were identified in two patients on a genome-wide 1 Mb resolution BAC array. A 2.3 Mb region of deletion overlap was defined using a tiling resolution chromosome 8 microarray. Sequence analysis of genes residing within this critical region revealed mutations in the CHD7 gene in 10 of the 17 CHARGE patients without microdeletions, including 7 heterozygous stop-codon mutations. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Primary Cilia Control Glucose Homeostasis Via Islet Paracrine Interactions
Primary cilia control glucose homeostasis via islet paracrine interactions Jing W. Hughesa,1, Jung Hoon Choa, Hannah E. Conwaya, Michael R. DiGrucciob, Xue Wen Ngb, Henry F. Rosemana, Damien Abreua, Fumihiko Uranoa, and David W. Pistonb aDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and bDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110 Edited by C. Ronald Kahn, Harvard Medical School, Boston, MA, and approved March 10, 2020 (received for review January 31, 2020) Pancreatic islets regulate glucose homeostasis through coordinated cellular synchronicity, and both intra- and intercellular signaling actions of hormone-secreting cells. What underlies the function of pathways that govern core islet functions, demonstrating that the islet as a unit is the close approximation and communication primary cilia are required for islet function as a unit and for the among heterogeneous cell populations, but the structural mediators maintenance of energy homeostasis. of islet cellular cross talk remain incompletely characterized. We generated mice specifically lacking β-cell primary cilia, a cellular or- Results ganelle that has been implicated in regulating insulin secretion, and INS1-Cre/IFT88-Flox Mice Lack β-Cell Cilia. To determine the role of found that the β-cell cilia are required for glucose sensing, calcium primary cilia in β-cell function, we generated βCKO mice by influx, insulin secretion, and cross regulation of α-andδ-cells. Pro- crossing INS1-Cre (16) with IFT88-Flox mice (17). The INS1- tein expression profiling in islets confirms perturbation in these Cre strain was chosen based on efficient and selective re- cellular processes and reveals additional targets of cilia-dependent combination in β-cells and established lack of expression in the signaling. -
Leber Congenital Amaurosis Due to CEP290 Mutations – Severe Vision Impairment with a High Unmet Medical Need: a Review Author and Journal Details: Bart P
This plain-language summary (or PLS) describes a paper on Leber congenital amaurosis 10 that was published in a medical journal called “Retina”. Title of the paper: Leber congenital amaurosis due to CEP290 mutations – severe vision impairment with a high unmet medical need: a review Author and journal details: Bart P. Leroy, David G. Birch, Jacque L. Duncan, Byron L. Lam, Robert K. Koenekoop, Fernanda B. O. Porto, Stephen R. Russel, Aniz Girach. Retina 2021;doi:10.1097/IAE.0000000000003133. Online ahead of print. What does this paper report on? • The authors of this paper reviewed what scientists know about the genetic eye disease called Leber congenital amaurosis 10 (also known as LCA10). They looked at the scientific articles on this subject that have been published in high-quality medical journals Why was this research needed? • Tying together separate pieces of scientific evidence about a disease can help us to understand the disease better. It also helps identify where there may be areas of care for people with the disease that need to be improved. We call these gaps “unmet medical needs” • Bringing evidence together in this way is especially important for rare diseases as it improves awareness among healthcare professionals of the needs of people living with the disease The authors of the paper are expert eye doctors working at specialist centers in Belgium, Brazil, Canada, and the USA; one of the authors is an employee of ProQR Therapeutics. This PLS has been developed in collaboration with Bart Leroy (an author on the original paper), Francesca Diodati and Matthew Carr, with medical writing assistance provided by ApotheCom. -
Genomic Aberrations Associated with Erlotinib Resistance in Non-Small Cell Lung Cancer Cells
ANTICANCER RESEARCH 33: 5223-5234 (2013) Genomic Aberrations Associated with Erlotinib Resistance in Non-small Cell Lung Cancer Cells MASAKUNI SERIZAWA1, TOSHIAKI TAKAHASHI2, NOBUYUKI YAMAMOTO2,3 and YASUHIRO KOH1 1Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka, Japan; 2Division of Thoracic Oncology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka, Japan; 3Third Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama, Japan Abstract. Background/Aim: Mechanisms of resistance to mutations develop resistance, usually within one year of epidermal growth factor receptor (EGFR)-tyrosine kinase treatment. Therefore, there is an urgent need to elucidate the inhibitors (TKIs) in non-small cell lung cancer (NSCLC) underlying mechanisms of resistance in such tumors to are not fully-understood. In this study we aimed to overcome this obstacle (11-14, 17, 24). Recent studies elucidate remaining unknown mechanisms using erlotinib- suggest that mechanisms of acquired resistance to EGFR- resistant NSCLC cells. Materials and Methods: We TKIs can be categorized into three groups: occurrence of performed array comparative genomic hybridization genetic alterations, activation of downstream pathways via (aCGH) to identify genomic aberrations associated with bypass signaling, and phenotypic transformation (15, 16, 21); EGFR-TKI resistance in erlotinib-resistant PC-9ER cells. therapeutic strategies to overcome these resistance Real-time polymerase chain reaction (PCR) and mechanisms are under development. However, although the immunoblot analyses were performed to confirm the results causes of acquired resistance to EGFR-TKIs have been of aCGH. Results: Among the five regions with copy investigated, in more than 30% of patients with acquired number gain detected in PC-9ER cells, we focused on resistance to EGFR-TKI treatment, the mechanisms remain 22q11.2-q12.1 including v-crk avian sarcoma virus CT10 unknown (15). -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like, -
AP1B1 Rabbit Polyclonal Antibody – TA323221 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA323221 AP1B1 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IHC Recommended Dilution: ELISA: 1:1000-5000, IHC: 1:25-100 Reactivity: Human, Mouse, Rat Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: Synthetic peptide corresponding to a region derived from 18-30 amino acids of Human Adapter-related protein complex 1 subunit beta-1 Formulation: PBS pH7.3, 0.05% NaN3, 50% glycerol Concentration: lot specific Purification: Antigen affinity purification Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Gene Name: adaptor related protein complex 1 beta 1 subunit Database Link: NP_001118 Entrez Gene 11764 MouseEntrez Gene 29663 RatEntrez Gene 162 Human Q10567 Background: Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex; where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large; one medium; and one small adaptin subunit. The protein encoded by this gene serves as one of the large subunits of this complex and is a member of the adaptin protein family. This gene is a candidate meningioma gene. Alternative splicing results in multiple transcript variants. Synonyms: ADTB1; AP105A; BAM22; CLAPB2 Protein Pathways: Lysosome This product is to be used for laboratory only. -
Speech Sound Disorder Influenced by a Locus in 15Q14 Region
Behav Genet DOI 10.1007/s10519-006-9090-7 ORIGINAL PAPER Speech Sound Disorder Influenced by a Locus in 15q14 Region Catherine M. Stein Æ Christopher Millard Æ Amy Kluge Æ Lara E. Miscimarra Æ Kevin C. Cartier Æ Lisa A. Freebairn Æ Amy J. Hansen Æ Lawrence D. Shriberg Æ H. Gerry Taylor Æ Barbara A. Lewis Æ Sudha K. Iyengar Received: 27 September 2005 / Accepted: 23 May 2006 Ó Springer Science+Business Media, Inc. 2006 Abstract Despite a growing body of evidence in- phonological memory, and that linkage at D15S118 was dicating that speech sound disorder (SSD) has an un- potentially influenced by a parent-of-origin effect derlying genetic etiology, researchers have not yet (LOD score increase from 0.97 to 2.17, P = 0.0633). identified specific genes predisposing to this condition. These results suggest shared genetic determinants in The speech and language deficits associated with SSD this chromosomal region for SSD, autism, and PWS/AS. are shared with several other disorders, including dys- lexia, autism, Prader-Willi Syndrome (PWS), and An- Keywords Phonology Æ Speech Æ Language Æ gelman’s Syndrome (AS), raising the possibility of gene Parent-of-origin Æ Allele-sharing sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also Introduction shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD Speech–sound disorder (SSD) is a common communi- phenotypes and microsatellite markers on the chromo- cation disorder of unknown etiology with an estimated some 15q14–21 region, which has been associated with prevalence of 15.2% in children at age 3, persisting in autism, PWS/AS, and dyslexia.