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články
články
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Source: BMČ - články
Title
Assessing average somatic CAG repeat instability at the protein level / H. Aviolat, RM. Pinto, E. Godschall, R. Murtha, HE. Richey, E. Sapp, P. Vodicka, VC. Wheeler, KB. Kegel-Gleason, M. DiFiglia,
Author
Aviolat, Hubert
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Pinto, Ricardo Mouro
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Godschall, Elizabeth
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Murtha, Ryan
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Richey, Hannah E
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Sapp, Ellen
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Vodicka, Petr
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Research Center PIGMOD, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Libechov, Czech Republic.

Wheeler, Vanessa C
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Kegel-Gleason, Kimberly B
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

DiFiglia, Marian
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. difiglia@helix.mgh.harvard.edu.

Cited source
Scientific reports. 2019, roč. 9, č. 1, s. 19152. ISSN: 2045-2322; (OCoLC)732869387.
Date of issue
2019
Language
angličtina
Country
Spojené království
Document type
články
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Pubmed ID
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Record number
bmc20028707
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English Abstract
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 MW1 Ab 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 HdhQ140 KI mice and in human HD postmortem cortex. This work establishes that CAG repeat instability in mutant HTT is reflected at the protein level.
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