From single variants to protein cascades : Multiscale modeling of single nucleotide variant sets in genetic disorders

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2016
Autor:innen
Müller, Sabine C.
Backes, Christina
Haas, Jan
Meder, Benjamin
Meese, Eckart
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes. We developed a multiscale pipeline to systematically analyze the existence of quantitative effects of multiple nsSNVs and gene combinations in single individuals on pathogenicity. Based on this pipeline, we detected in a data set of 842 nsSNVs discovered in 76 genes related to cardiomyopathies, associated nsSNV combinations in seven genes present in at least 70% of all 639 patient samples, but not in a control cohort of healthy humans. Structural analyses of these revealed primarily an influence on the protein stability. For amino acid substitutions located at the protein surface, we generally observed a proximity to putative binding pockets. To computationally analyze cumulative effects and their impact, pathogenicity methods are currently being developed. Our approach supports this process, as shown on the example of a cardiac phenotype but can be likewise applied to other diseases such as cancer.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690MÜLLER, Sabine C., Björn SOMMER, Christina BACKES, Jan HAAS, Benjamin MEDER, Eckart MEESE, Andreas KELLER, 2016. From single variants to protein cascades : Multiscale modeling of single nucleotide variant sets in genetic disorders. In: The Journal of Biological Chemistry : JBC. 2016, 291(4), pp. 1582-1590. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M115.695247
BibTex
@article{Muller2016singl-36878,
  year={2016},
  doi={10.1074/jbc.M115.695247},
  title={From single variants to protein cascades : Multiscale modeling of single nucleotide variant sets in genetic disorders},
  number={4},
  volume={291},
  issn={0021-9258},
  journal={The Journal of Biological Chemistry : JBC},
  pages={1582--1590},
  author={Müller, Sabine C. and Sommer, Björn and Backes, Christina and Haas, Jan and Meder, Benjamin and Meese, Eckart and Keller, Andreas}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36878">
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/36878"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Meese, Eckart</dc:contributor>
    <dc:contributor>Backes, Christina</dc:contributor>
    <dcterms:title>From single variants to protein cascades : Multiscale modeling of single nucleotide variant sets in genetic disorders</dcterms:title>
    <dc:contributor>Keller, Andreas</dc:contributor>
    <dc:contributor>Sommer, Björn</dc:contributor>
    <dc:creator>Meder, Benjamin</dc:creator>
    <dc:creator>Keller, Andreas</dc:creator>
    <dc:creator>Sommer, Björn</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36"/>
    <dc:creator>Meese, Eckart</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/36"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-01-23T09:49:48Z</dc:date>
    <dc:creator>Haas, Jan</dc:creator>
    <dc:contributor>Haas, Jan</dc:contributor>
    <dcterms:issued>2016</dcterms:issued>
    <dc:creator>Müller, Sabine C.</dc:creator>
    <dc:contributor>Müller, Sabine C.</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-01-23T09:49:48Z</dcterms:available>
    <dc:contributor>Meder, Benjamin</dc:contributor>
    <dcterms:abstract xml:lang="eng">Understanding the role of genetics in disease has become a central part of medical research. Non-synonymous single nucleotide variants (nsSNVs) in coding regions of human genes frequently lead to pathological phenotypes. Beyond single variations, the individual combination of nsSNVs may add to pathogenic processes. We developed a multiscale pipeline to systematically analyze the existence of quantitative effects of multiple nsSNVs and gene combinations in single individuals on pathogenicity. Based on this pipeline, we detected in a data set of 842 nsSNVs discovered in 76 genes related to cardiomyopathies, associated nsSNV combinations in seven genes present in at least 70% of all 639 patient samples, but not in a control cohort of healthy humans. Structural analyses of these revealed primarily an influence on the protein stability. For amino acid substitutions located at the protein surface, we generally observed a proximity to putative binding pockets. To computationally analyze cumulative effects and their impact, pathogenicity methods are currently being developed. Our approach supports this process, as shown on the example of a cardiac phenotype but can be likewise applied to other diseases such as cancer.</dcterms:abstract>
    <dc:creator>Backes, Christina</dc:creator>
    <dc:language>eng</dc:language>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen