Phenodb, Genematcher and Variantmatcher, Tools for Analysis and Sharing of Sequence Data Elizabeth Wohler1†, Renan Martin1†, Sean Grifth2, Eliete Da S
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4Q27 Deletion and 7Q36.1 Microduplication in a Patient With
Wu et al. BMC Medical Genomics (2020) 13:31 https://doi.org/10.1186/s12920-020-0697-y CASE REPORT Open Access 4q27 deletion and 7q36.1 microduplication in a patient with multiple malformations and hearing loss: a case report Maolan Wu, Xiangrong Zheng* , Xia Wang, Guoyuan Zhang and Jian Kuang Abstract Background: Chromosome deletions of the long arm of chromosome 4 in 4q syndrome are characterized by mild facial and digital dysmorphism, developmental delay, growth retardation, and skeletal and cardiac anomalies, which is regarded as an autism spectrum disorder. Moreover, some scarce reports indicate that patients with 4q interstitial deletion and 7p duplication may present symptoms associated with hearing loss. Case presentation: A boy with a severe developmental delay not only post-natal but also intrauterine and several dysmorphic features including microcephaly, ocular hypertelorism, exophthalmos, low-set ears, single palmar flexion crease, and overlapping toes presented discontinued cyanosis and recurrent respiratory infections. MRI, BAEP, echocardiogram and bronchoscopy revealed that he had persistent falcine sinus with a thin corpus callosum, left auditory pathway disorder, patent foramen ovale (2 mm), and tracheobronchomalacia with the right superior bronchus arising from the lateral posterior wall of the right main bronchus. Finally, the patient died with severe pneumonia at 10 months. Array CGH revealed a 23.62 Mb deletion at chromosome 4q27, arr [hg19] 4q27-q31.21 (121, 148, 089–144, 769, 263) × 1, and a 0.85 Mb duplication at chromosome 7q36.1, arr [hg19] 7q36.1-q36.2 (152, 510, 685–153, 363,5 98) × 3. It is rare for 4q syndrome cases or 7q duplications previously reported to have a hearing disorder, pulmonary dysplasia, and pulmonary arterial hypertension. -
Exomic Sequencing of Immune-Related Genes Reveals Novel Candidate Variants Associated with Alopecia Universalis
Exomic Sequencing of Immune-Related Genes Reveals Novel Candidate Variants Associated with Alopecia Universalis Seungbok Lee1,2., Seung Hwan Paik3., Hyun-Jin Kim1,2, Hyeong Ho Ryu3, Soeun Cha1, Seong Jin Jo3, Hee Chul Eun3,4,5, Jeong-Sun Seo1,2,6,7,8, Jong-Il Kim1,2,6,7*, Oh Sang Kwon3,4,5* 1 Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea, 2 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea, 3 Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea, 4 Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea, 5 Institute of Dermatological Science, Seoul National University College of Medicine, Seoul, Korea, 6 Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea, 7 Psoma Therapeutics Inc., Seoul, Korea, 8 Macrogen Inc., Seoul, Korea Abstract Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p,1.9261023). -
Genome-Wide Pooling Approach Identifies SPATA5 As a New Susceptibility Locus for Alopecia Areata Regina C
Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata Regina C. Betz, Lina M. Forstbauer, Felix F. Brockschmidt, Valentina Moskvina, Christine Herold, Silke Redler, Alexandra Herzog, Axel M. Hillmer, Christian Meesters, Stefanie Heilmann, et al. To cite this version: Regina C. Betz, Lina M. Forstbauer, Felix F. Brockschmidt, Valentina Moskvina, Christine Herold, et al.. Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata. European Journal of Human Genetics, Nature Publishing Group, 2011, 10.1038/ejhg.2011.185. hal- 00691329 HAL Id: hal-00691329 https://hal.archives-ouvertes.fr/hal-00691329 Submitted on 26 Apr 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for 2 alopecia areata 3 4 Lina M. Forstbauer1*, Felix F. Brockschmidt1,2*, Valentina Moskvina3, Christine 5 Herold4, Silke Redler1, Alexandra Herzog1, Axel M. Hillmer5, Christian Meesters4,6, 6 Stefanie Heilmann1,2, Florian Albert1, Margrieta Alblas1,2, Sandra Hanneken7, Sibylle 7 Eigelshoven7, Kathrin A. Giehl8, Dagny Jagielska1,9, Ulrike Blume-Peytavi9, Natalie 8 Garcia Bartels9, Jennifer Kuhn10,11,12, Hans Christian Hennies10,11,12, Matthias 9 Goebeler13, Andreas Jung13, Wiebke K. -
Gene Ontology Functional Annotations and Pleiotropy
Network based analysis of genetic disease associations Sarah Gilman Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2013 Sarah Gilman All Rights Reserved ABSTRACT Network based analysis of genetic disease associations Sarah Gilman Despite extensive efforts and many promising early findings, genome-wide association studies have explained only a small fraction of the genetic factors contributing to common human diseases. There are many theories about where this “missing heritability” might lie, but increasingly the prevailing view is that common variants, the target of GWAS, are not solely responsible for susceptibility to common diseases and a substantial portion of human disease risk will be found among rare variants. Relatively new, such variants have not been subject to purifying selection, and therefore may be particularly pertinent for neuropsychiatric disorders and other diseases with greatly reduced fecundity. Recently, several researchers have made great progress towards uncovering the genetics behind autism and schizophrenia. By sequencing families, they have found hundreds of de novo variants occurring only in affected individuals, both large structural copy number variants and single nucleotide variants. Despite studying large cohorts there has been little recurrence among the genes implicated suggesting that many hundreds of genes may underlie these complex phenotypes. The question -
Rabbit Anti-SPATA5/FITC Conjugated Antibody
SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-SPATA5/FITC Conjugated antibody SL17631R-FITC Product Name: Anti-SPATA5/FITC Chinese Name: FITC标记的精子发生相关蛋白2抗体 AFG2; ATPase family gene 2 homolog; ATPase family protein 2 homolog; SPAF; Alias: Spermatogenesis associated 5; Spermatogenesis associated factor SPAF; Spermatogenesis-associated factor protein. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Dog,Pig,Cow, ICC=1:50-200IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 98kDa Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human SPATA5 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01Mwww.sunlongbiotech.com TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: SPATA5 is an 893 amino acid protein that localizes to cytoplasm and mitochondrion, and may be involved in morphological and functional mitochondrial transformations during spermatogenesis. Existing as three alternatively spliced isoforms, SPATA5 Product Detail: belongs to the AAA ATPase family and the AFG2 subfamily. The gene that encodes SPATA5 consists of more than 396,000 bases and maps to human chromosome 4q28.1. -
Identification Des Bases Moléculaires Et Physiopathologiques Des Syndromes Oro-Facio-Digitaux Ange-Line Bruel
Identification des bases moléculaires et physiopathologiques des syndromes oro-facio-digitaux Ange-Line Bruel To cite this version: Ange-Line Bruel. Identification des bases moléculaires et physiopathologiques des syndromes oro-facio- digitaux. Génétique. Université de Bourgogne, 2016. Français. NNT : 2016DIJOS043. tel-01635713 HAL Id: tel-01635713 https://tel.archives-ouvertes.fr/tel-01635713 Submitted on 15 Nov 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE DE BOURGOGNE UFR des Sciences de Santé THÈSE Pour obtenir le grade de Docteur de l’Université de Bourgogne Discipline : Sciences de la vie par Ange-Line Bruel 21 Septembre 2016 Identification des bases moléculaires et physiopathologiques des syndromes oro-facio-digitaux Directeur de thèse Pr Christel Thauvin-Robinet Co-directeur de thèse Dr Laurence Jego Dr Jean-Baptiste Rivière Jury Pr Faivre Laurence, Président Pr Thauvin-Robinet Christel, Directeur de thèse Dr Saunier Sophie, Rapporteur Pr Geneviève David, Rapporteur Pr Attié-Bittach Tania, Examinateur 1 A ma famille 2 Remerciements Je voudrais remercier en premier lieu Laurence Faivre, de m’avoir accueillie au sein du laboratoire Génétique des Anomalies du Développement, pour l’intérêt porté à mes travaux et pour son soutien. -
Loss-Of-Function Mutations in UDP-Glucose 6-Dehydrogenase Cause Recessive Developmental Epileptic Encephalopathy
ARTICLE https://doi.org/10.1038/s41467-020-14360-7 OPEN Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy Holger Hengel et al.# Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of 1234567890():,; germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteogly- cans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH sta- bility, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy. #A full list of authors and their affiliations appears at the end of the paper. NATURE COMMUNICATIONS | (2020) 11:595 | https://doi.org/10.1038/s41467-020-14360-7 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-14360-7 evelopmental epileptic encephalopathies are a clinically A44V variant, identified in the Palestinian index family, was also Dand genetically heterogeneous group of devastating dis- found in two additional families from Puerto Rico (F11) and from orders characterized by severe epileptic seizures that are Spain (F13) indicative of independent but recurrent mutation in accompanied by developmental delay or regression1. -
2014-Platform-Abstracts.Pdf
American Society of Human Genetics 64th Annual Meeting October 18–22, 2014 San Diego, CA PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Saturday 41 Statistical Methods for Population 5:30pm–6:50pm: Session 2: Plenary Abstracts Based Studies Room 20A #198–#205 Featured Presentation I (4 abstracts) Hall B1 #1–#4 42 Genome Variation and its Impact on Autism and Brain Development Room 20BC #206–#213 Sunday 43 ELSI Issues in Genetics Room 20D #214–#221 1:30pm–3:30pm: Concurrent Platform Session A (12–21): 44 Prenatal, Perinatal, and Reproductive 12 Patterns and Determinants of Genetic Genetics Room 28 #222–#229 Variation: Recombination, Mutation, 45 Advances in Defining the Molecular and Selection Hall B1 Mechanisms of Mendelian Disorders Room 29 #230–#237 #5-#12 13 Genomic Studies of Autism Room 6AB #13–#20 46 Epigenomics of Normal Populations 14 Statistical Methods for Pedigree- and Disease States Room 30 #238–#245 Based Studies Room 6CF #21–#28 15 Prostate Cancer: Expression Tuesday Informing Risk Room 6DE #29–#36 8:00pm–8:25am: 16 Variant Calling: What Makes the 47 Plenary Abstracts Featured Difference? Room 20A #37–#44 Presentation III Hall BI #246 17 New Genes, Incidental Findings and 10:30am–12:30pm:Concurrent Platform Session D (49 – 58): Unexpected Observations Revealed 49 Detailing the Parts List Using by Exome Sequencing Room 20BC #45–#52 Genomic Studies Hall B1 #247–#254 18 Type 2 Diabetes Genetics Room 20D #53–#60 50 Statistical Methods for Multigene, 19 Genomic Methods in Clinical Practice Room 28 #61–#68 Gene Interaction -
Systematic Discovery of Endogenous Human Ribonucleoprotein Complexes
bioRxiv preprint doi: https://doi.org/10.1101/480061; this version posted November 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Systematic discovery of endogenous human ribonucleoprotein complexes Anna L. Mallam1,2,3,§,*, Wisath Sae-Lee1,2,3, Jeffrey M. Schaub1,2,3, Fan Tu1,2,3, Anna Battenhouse1,2,3, Yu Jin Jang1, Jonghwan Kim1, Ilya J. Finkelstein1,2,3, Edward M. Marcotte1,2,3,§, Kevin Drew1,2,3,§,* 1 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA 2 Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA 3 Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA § Correspondence: [email protected] (A.L.M.), [email protected] (E.M.M.), [email protected] (K.D.) * These authors contributed equally to this work Short title: A resource of human ribonucleoprotein complexes Summary: An exploration of human protein complexes in the presence and absence of RNA reveals endogenous ribonucleoprotein complexes ! 1! bioRxiv preprint doi: https://doi.org/10.1101/480061; this version posted November 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Ribonucleoprotein (RNP) complexes are important for many cellular functions but their prevalence has not been systematically investigated. -
SPATA5 Mutations Cause a Distinct Autosomal Recessive Phenotype of Intellectual Disability, Hypotonia and Hearing Loss Rebecca Buchert1,2, Addie I
Buchert et al. Orphanet Journal of Rare Diseases (2016) 11:130 DOI 10.1186/s13023-016-0509-9 LETTER TO THE EDITOR Open Access SPATA5 mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss Rebecca Buchert1,2, Addie I. Nesbitt3, Hasan Tawamie1, Ian D. Krantz4, Livija Medne5, Ingo Helbig6,7, Dena R. Matalon4, André Reis1, Avni Santani3,8, Heinrich Sticht9 and Rami Abou Jamra1,10* Abstract We examined an extended, consanguineous family with seven individuals with severe intellectual disability and microcephaly. Further symptoms were hearing loss, vision impairment, gastrointestinal disturbances, and slow and asymmetric waves in the EEG. Linkage analysis followed by exome sequencing revealed a homozygous variant in SPATA5 (c.1822_1824del; p.Asp608del), which segregates with the phenotype in the family. Molecular modelling suggested a deleterious effect of the identified alterations on the protein function. In an unrelated family, we identified compound heterozygous variants in SPATA5 (c.[2081G > A];[989_991delCAA]; p.[Gly694Glu];[.Thr330del]) in a further individual with global developmental delay, infantile spasms, profound dystonia, and sensorineural hearing loss. Molecular modelling suggested an impairment of protein function in the presence of both variants. SPATA5 is a member of the ATPase associated with diverse activities (AAA) protein family and was very recently reported in one publication to be mutated in individuals with intellectual disability, epilepsy and hearing loss. Our results describe new, probably pathogenic variants in SPATA5 that were identified in individuals with a comparable phenotype. We thus independently confirm that bi-allelic pathogenic variants in SPATA5 cause a syndromic form of intellectual disability, and we delineate its clinical presentation. -
The Role of Recessive Inheritance in Early-Onset Epileptic Encephalopathies: a Combined Whole-Exome Sequencing and Copy Number Study
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2019 The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study Papuc, Sorina M ; Abela, Lucia ; Steindl, Katharina ; Begemann, Anaïs ; Simmons, Thomas L ; Schmitt, Bernhard ; Zweier, Markus ; Oneda, Beatrice ; Socher, Eileen ; Crowther, Lisa M ; Wohlrab, Gabriele ; Gogoll, Laura ; Poms, Martin ; Seiler, Michelle ; Papik, Michael ; Baldinger, Rosa ; Baumer, Alessandra ; Asadollahi, Reza ; Kroell-Seger, Judith ; Schmid, Regula ; Iff, Tobias ; Schmitt-Mechelke, Thomas ; Otten, Karoline ; Hackenberg, Annette ; Addor, Marie-Claude ; Klein, Andrea ; Azzarello-Burri, Silvia ; Sticht, Heinrich ; Joset, Pascal ; Plecko, Barbara ; Rauch, Anita Abstract: Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic en- cephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and un- targeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in 42% of cases with causative copy number variants in 6 patients (10%) and causative sequence variants in 16 established disease genes in 20 patients (32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. -
Genomic Approach in Idiopathic Intellectual Disability Maria De Fátima E Costa Torres
ESTUDOS DE 8 01 PDPGM 2 CICLO Genomic approach in idiopathic intellectual disability Maria de Fátima e Costa Torres D Autor. Maria de Fátima e Costa Torres D.ICBAS 2018 Genomic approach in idiopathic intellectual disability Genomic approach in idiopathic intellectual disability Maria de Fátima e Costa Torres SEDE ADMINISTRATIVA INSTITUTO DE CIÊNCIAS BIOMÉDICAS ABEL SALAZAR FACULDADE DE MEDICINA MARIA DE FÁTIMA E COSTA TORRES GENOMIC APPROACH IN IDIOPATHIC INTELLECTUAL DISABILITY Tese de Candidatura ao grau de Doutor em Patologia e Genética Molecular, submetida ao Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto Orientadora – Doutora Patrícia Espinheira de Sá Maciel Categoria – Professora Associada Afiliação – Escola de Medicina e Ciências da Saúde da Universidade do Minho Coorientadora – Doutora Maria da Purificação Valenzuela Sampaio Tavares Categoria – Professora Catedrática Afiliação – Faculdade de Medicina Dentária da Universidade do Porto Coorientadora – Doutora Filipa Abreu Gomes de Carvalho Categoria – Professora Auxiliar com Agregação Afiliação – Faculdade de Medicina da Universidade do Porto DECLARAÇÃO Dissertação/Tese Identificação do autor Nome completo _Maria de Fátima e Costa Torres_ N.º de identificação civil _07718822 N.º de estudante __ 198600524___ Email institucional [email protected] OU: [email protected] _ Email alternativo [email protected] _ Tlf/Tlm _918197020_ Ciclo de estudos (Mestrado/Doutoramento) _Patologia e Genética Molecular__ Faculdade/Instituto _Instituto de Ciências