Allelic Imbalance in TOR1A mRNA Expression in Manifesting and Non-Manifesting Carriers of the GAG-DeletionReportar como inadecuado




Allelic Imbalance in TOR1A mRNA Expression in Manifesting and Non-Manifesting Carriers of the GAG-Deletion - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Nucleic AcidsVolume 2012 2012, Article ID 985260, 5 pages

Research Article

Department of Neurology and Radiology Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA

Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA

Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA

Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA

Received 22 April 2012; Revised 13 July 2012; Accepted 16 July 2012

Academic Editor: Ben Berkhout

Copyright © 2012 Ioanna A. Armata et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Early onset dystonia EOD is associated with a 3bp-ΔGAG in-frame deletion in the TOR1A gene, which encodes for torsinA. Carriers of the mutant ΔGAG allele can either develop or escape a dystonic phenotype ~30% penetrance. The expression ratio of the two alleles could be important for the manifestation or prevention of the disease since wild-type WT torsinA is thought to have protective function. Absence of an antibody discriminating WT from ΔE torsinA has precluded the determination ΔE and WT torsinA levels in manifesting and nonmanifesting carriers. We performed quantitative analysis of TOR1A allele expression in manifesting MC and nonmanifesting NMC carriers using quantitative allele-specific PCR qASPCR to determine the levels of mutant versus WT torsinA mRNA. The technique described showed high degree of specificity in detecting the two alleles. The present study represents the first comprehensive analysis of biallelic expression of the TOR1A gene in lymphoblast and brain samples from patients and NMC relatives. We demonstrate that mRNA is transcribed from both the WT and ΔGAG allele in peripheral and neural tissues with a trend for increased expression of the ΔGAG allele compared to the WT in carriers regardless of their phenotype and thus cannot account for the reduced penetrance.





Autor: Ioanna A. Armata, Andreas I. Diplas, Laurie J. Ozelius, and Pullanipally Shashidharan

Fuente: https://www.hindawi.com/



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