Alt Haplotypes Refseq Curated Sequences Snps Dnase Clusters
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
Human Astrocytes: Structure and Functions in the Healthy Brain
Brain Struct Funct DOI 10.1007/s00429-017-1383-5 REVIEW Human astrocytes: structure and functions in the healthy brain Flora Vasile1 · Elena Dossi1 · Nathalie Rouach1 Received: 4 November 2016 / Accepted: 6 February 2017 © The Author(s) 2017. This article is published with open access at Springerlink.com Abstract Data collected on astrocytes’ physiology in the Introduction rodent have placed them as key regulators of synaptic, neu- ronal, network, and cognitive functions. While these find- Since the early discovery that the range of astroglial func- ings proved highly valuable for our awareness and appreci- tions extends considerably beyond passive structural sup- ation of non-neuronal cell significance in brain physiology, port, astrocytes have cemented their position as crucial early structural and phylogenic investigations of human determinants of proper neuronal function. Astrocytes are astrocytes hinted at potentially different astrocytic proper- now considered as full-fledged participants in brain cir- ties. This idea sparked interest to replicate rodent-based cuitry and processing, and display a large spectrum of studies on human samples, which have revealed an analo- functions at the cell level, such as the formation, matura- gous but enhanced involvement of astrocytes in neuronal tion and elimination of synapses, ionic homeostasis, clear- function of the human brain. Such evidence pointed to a ance of neurotransmitters, regulation of extracellular space central role of human astrocytes in sustaining more com- volume, and modulation of synaptic activity and plastic- plex information processing. Here, we review the current ity (Araque et al. 2014; Dallérac and Rouach 2016). It has state of our knowledge of human astrocytes regarding their additionally been demonstrated that they are involved in structure, gene profile, and functions, highlighting the dif- rhythm generation and neuronal network patterns (Fellin ferences with rodent astrocytes. -
Transcriptomic Profiling of Ca Transport Systems During
cells Article Transcriptomic Profiling of Ca2+ Transport Systems during the Formation of the Cerebral Cortex in Mice Alexandre Bouron Genetics and Chemogenomics Lab, Université Grenoble Alpes, CNRS, CEA, INSERM, Bâtiment C3, 17 rue des Martyrs, 38054 Grenoble, France; [email protected] Received: 29 June 2020; Accepted: 24 July 2020; Published: 29 July 2020 Abstract: Cytosolic calcium (Ca2+) transients control key neural processes, including neurogenesis, migration, the polarization and growth of neurons, and the establishment and maintenance of synaptic connections. They are thus involved in the development and formation of the neural system. In this study, a publicly available whole transcriptome sequencing (RNA-Seq) dataset was used to examine the expression of genes coding for putative plasma membrane and organellar Ca2+-transporting proteins (channels, pumps, exchangers, and transporters) during the formation of the cerebral cortex in mice. Four ages were considered: embryonic days 11 (E11), 13 (E13), and 17 (E17), and post-natal day 1 (PN1). This transcriptomic profiling was also combined with live-cell Ca2+ imaging recordings to assess the presence of functional Ca2+ transport systems in E13 neurons. The most important Ca2+ routes of the cortical wall at the onset of corticogenesis (E11–E13) were TACAN, GluK5, nAChR β2, Cav3.1, Orai3, transient receptor potential cation channel subfamily M member 7 (TRPM7) non-mitochondrial Na+/Ca2+ exchanger 2 (NCX2), and the connexins CX43/CX45/CX37. Hence, transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1), transmembrane protein 165 (TMEM165), and Ca2+ “leak” channels are prominent intracellular Ca2+ pathways. The Ca2+ pumps sarco/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) and plasma membrane Ca2+ ATPase 1 (PMCA1) control the resting basal Ca2+ levels. -
GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort
G C A T T A C G G C A T genes Article GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort Paula Buonfiglio 1 , Carlos D. Bruque 2,3 , Leonela Luce 4,5, Florencia Giliberto 4,5, Vanesa Lotersztein 6, Sebastián Menazzi 7, Bibiana Paoli 8, Ana Belén Elgoyhen 1,9 and Viviana Dalamón 1,* 1 Laboratorio de Fisiología y Genética de la Audición, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular “Dr. Héctor N. Torres”, Consejo Nacional de Investigaciones Científicas y Técnicas—INGEBI/CONICET, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina; paulabuonfi[email protected] (P.B.); [email protected] (A.B.E.) 2 Centro Nacional de Genética Médica, ANLIS-Malbrán, C1425 Ciudad Autónoma de Buenos Aires, Argentina; [email protected] 3 Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas—IBYME/CONICET, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina 4 Laboratorio de Distrofinopatías, Cátedra de Genética, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, C1113AAD Ciudad Autónoma de Buenos Aires, Argentina; [email protected] (L.L.); gilibertofl[email protected] (F.G.) 5 Instituto de Inmunología, Genética y Metabolismo—INIGEM/CONICET, Universidad de Buenos Aires, C1113AAD Ciudad Autónoma de Buenos Aires, Argentina 6 Servicio de Genética, Hospital Militar Central “Dr. Cosme Argerich”, C1426 Ciudad Autónoma de Buenos Aires, Argentina; [email protected] 7 Servicio de Genética, Hospital de Clínicas “José de San Martín”, -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
The Role of Potassium Recirculation in Cochlear Amplification
The role of potassium recirculation in cochlear amplification Pavel Mistrika and Jonathan Ashmorea,b aUCL Ear Institute and bDepartment of Neuroscience, Purpose of review Physiology and Pharmacology, UCL, London, UK Normal cochlear function depends on maintaining the correct ionic environment for the Correspondence to Jonathan Ashmore, Department of sensory hair cells. Here we review recent literature on the cellular distribution of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK potassium transport-related molecules in the cochlea. Tel: +44 20 7679 8937; fax: +44 20 7679 8990; Recent findings e-mail: [email protected] Transgenic animal models have identified novel molecules essential for normal hearing Current Opinion in Otolaryngology & Head and and support the idea that potassium is recycled in the cochlea. The findings indicate that Neck Surgery 2009, 17:394–399 extracellular potassium released by outer hair cells into the space of Nuel is taken up by supporting cells, that the gap junction system in the organ of Corti is involved in potassium handling in the cochlea, that the gap junction system in stria vascularis is essential for the generation of the endocochlear potential, and that computational models can assist in the interpretation of the systems biology of hearing and integrate the molecular, electrical, and mechanical networks of the cochlear partition. Such models suggest that outer hair cell electromotility can amplify over a much broader frequency range than expected from isolated cell studies. Summary These new findings clarify the role of endolymphatic potassium in normal cochlear function. They also help current understanding of the mechanisms of certain forms of hereditary hearing loss. -
Abstracts from the 51St European Society of Human Genetics Conference: Electronic Posters
European Journal of Human Genetics (2019) 27:870–1041 https://doi.org/10.1038/s41431-019-0408-3 MEETING ABSTRACTS Abstracts from the 51st European Society of Human Genetics Conference: Electronic Posters © European Society of Human Genetics 2019 June 16–19, 2018, Fiera Milano Congressi, Milan Italy Sponsorship: Publication of this supplement was sponsored by the European Society of Human Genetics. All content was reviewed and approved by the ESHG Scientific Programme Committee, which held full responsibility for the abstract selections. Disclosure Information: In order to help readers form their own judgments of potential bias in published abstracts, authors are asked to declare any competing financial interests. Contributions of up to EUR 10 000.- (Ten thousand Euros, or equivalent value in kind) per year per company are considered "Modest". Contributions above EUR 10 000.- per year are considered "Significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal Genetics then compared this data to de novo cases where research based PO studies were completed (N=57) in NY. E-P01.01 Results: MFSIQ (66.4) for familial deletions was Parent of origin in familial 22q11.2 deletions impacts full statistically lower (p = .01) than for de novo deletions scale intelligence quotient scores (N=399, MFSIQ=76.2). MFSIQ for children with mater- nally inherited deletions (63.7) was statistically lower D. E. McGinn1,2, M. Unolt3,4, T. B. Crowley1, B. S. Emanuel1,5, (p = .03) than for paternally inherited deletions (72.0). As E. H. Zackai1,5, E. Moss1, B. Morrow6, B. Nowakowska7,J. compared with the NY cohort where the MFSIQ for Vermeesch8, A. -
Supplementary Table 2
Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942 -
1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders. -
Whole Exome Sequencing Identified Mutations Causing Hearing Loss In
Whole exome sequencing identied mutations causing hearing loss in ve consanguineous Pakistan families Yingjie Zhou Second Hospital of Hebei Medical University Muhammad Tariq National Institue for Biotechnology and Genetic Engineering Sijie He(Former Corresponding Author) BGI https://orcid.org/0000-0002-4418-1785 Uzma Abdullah NIBGE Jianguo Zhang(New Corresponding Author) ( [email protected] ) BGI Shahid Mahmood Baig NIBGE Research article Keywords: hearing loss, whole exome sequencing, consanguineous pedigrees, clinical detection Posted Date: April 8th, 2020 DOI: https://doi.org/10.21203/rs.2.19325/v2 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Version of Record: A version of this preprint was published on July 18th, 2020. See the published version at https://doi.org/10.1186/s12881-020-01087-x. Page 1/10 Abstract Background Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and ecient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES). Methods We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them. Results Variants in 7 genes were identied and validated in these pedigrees. We identied single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). -
Molecular Test for Non Syndromic Hearing Loss
Molecular Testing for Connexin 26 (GJB2) and Connexin 30 (GJB6) Mutations Associated with Non Syndromic Hearing Loss The UNC Hospitals Molecular Genetics Laboratory offers DNA sequencing of the coding region of the connexin 26 (GJB2) gene and analysis of deletions in the connexin 30 (GJB6) gene to detect mutations that are associated with hereditary nonsyndromic hearing loss. Biology of the disease : Profound congenital hearing loss affects approximately 1 in 1000 infants. Approximately 50% of cases have a genetic cause, and 70% of these genetic cases are classified as nonsyndromic, meaning that hearing loss is the only clinical finding. The remaining 30% have additional signs or symptoms with over 400 different syndromes described. Familial nonsyndromic hearing loss (NSHL) is primarily sensorineural, with the mode of inheritance being 77% autosomal recessive, 22% autosomal dominant, and the remainder X-linked or mitochondrial. Several genetic loci have been mapped, including the DFNB1 locus on chromosome 13q12 containing the gap junction beta 2 (GJB2) gene encoding connexin 26 protein and the GJB6 gene encoding connexin 30 protein. Connexins 26 and 30, transmembrane proteins expressed in the inner ear, form ion channels regulating intercellular communication. Numerous disease-causing mutations in GJB2 have been identified, the most common of which is 35delG, which is found in over two- thirds of Caucasians with DFNB1-linked hearing loss. It is estimated that 35delG is responsible for 10% of all deafness and 20% of all hereditary hearing impairment. Other mutations in GJB2 are more common in other ethnic groups; for example, 167delT accounts for majority of cases of autosomal recessive NSHL in people of Ashkenazi Jewish ethnicity. -
Genetic Testing for Hereditary Hearing Loss
MEDICAL POLICY POLICY TITLE GENETIC TESTING FOR HEREDITARY HEARING LOSS POLICY NUMBER MP-2.319 Original Issue Date (Created): 2/1/2014 Most Recent Review Date (Revised): 8/10/2020 Effective Date: 11/1/2020 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER REFERENCES CODING INFORMATION POLICY HISTORY I. POLICY Genetic testing for hereditary hearing loss mutations (GJB2, GJB6 and other hereditary hearing loss-related genes) in individuals with suspected hearing loss to confirm the diagnosis of hereditary hearing loss (see Policy Guidelines) may be considered medically necessary. Preconception genetic testing (carrier testing) for hereditary hearing loss–related genes (GJB2, GJB6 and other hereditary hearing loss related genes) in parents may be considered medically necessary when at least one of the following conditions has been met: Offspring with hereditary hearing loss; OR One or both parents with suspected hereditary hearing loss; OR First- or second-degree relative affected with hereditary hearing loss; OR First-degree relative with offspring who is affected with hereditary hearing loss Genetic testing for hereditary hearing loss genes is considered investigational for all other situations, including, but not limited to, testing patients without hearing loss (except as addressed in related policies, e.g., MP-7.009 Preimplantation Genetic Testing). There is insufficient evidence to support a conclusion concerning the health outcomes or benefits associated with this procedure. Policy Guidelines Hereditary hearing loss can be classified as syndromic or nonsyndromic. The definition of nonsyndromic hearing loss is hearing loss not associated with other physical signs and symptoms at the time of hearing loss presentation. It is differentiated from syndromic hearing loss, which is hearing loss associated with other signs and symptoms characteristic of a specific syndrome. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Deafness Non-Syndromic Sensorineural Autosomal Dominant Panel Test Code D4400 Test Summary This test analyzes 30 genes associated with non-syndromic sensorineural autosomal dominant deafness. Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing Individuals with hearing loss without any other signs or symptoms associated with a genetic condition Family history of hearing loss consistent with autosomal dominant inheritance Test Description This panel analyzes 30 genes that have been associated with autosomal dominant non-syndromic sensorineural deafness. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Between 2-3 per 1,000 children in the United States are born with detectable hearing loss in one or both ears. The prevalance of hearing loss increases with age. By age 12, hearing loss affects 1 in 8 individuals. Hearing loss can be caused by both environmental and genetic causes. Non- syndromic hearing loss is a partial or complete loss of hearing that is not associated with other signs or symptoms. Mutations in many genes have been identified in families with autosomal dominant non-syndromic hearing loss.