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Assessing average somatic CAG repeat instability at the protein level

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F19%3A00518791" target="_blank" >RIV/67985904:_____/19:00518791 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.nature.com/articles/s41598-019-55202-x" target="_blank" >https://www.nature.com/articles/s41598-019-55202-x</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1038/s41598-019-55202-x" target="_blank" >10.1038/s41598-019-55202-x</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Assessing average somatic CAG repeat instability at the protein level

  • Original language description

    Sandwich ELISA-based methods use Abs that target the expanded polyglutamine (polyQ) tract to quantify mutant huntingtin (mHTT). Using Meso Scale Discovery (MSD) assay, the mHTT signal detected with MW1Ab correlated with polyQ length and doubled with a difference of only 7 glutamine residues between equivalent amounts of purified mHTTexon1 proteins. Similar polyQ length-dependent effects on MSD signals were confirmed using endogenous full length mHTT from brains of Huntington's disease (HD) knock-in (KI) mice. We used this avidity bias to devise a method to assess average CAG repeat instability at the protein level in a mixed population of HTT proteins present in tissues. Signal detected for average polyQ length quantification at the protein level by our method exhibited a strong correlation with average CAG repeat length at the genomic DNA level determined by PCR method in striatal tissue homogenates from Hdh(Q140) KI mice and in human HD postmortem cortex. This work establishes that CAG repeat instability in mutant HTT is reflected at the protein level.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Scientific Reports

  • ISSN

    2045-2322

  • e-ISSN

  • Volume of the periodical

    9

  • Issue of the periodical within the volume

    DEC 16

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    14

  • Pages from-to

    19152

  • UT code for WoS article

    000503171600001

  • EID of the result in the Scopus database

    2-s2.0-85076559713