Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease
Φόρτωση...
Ημερομηνία
Συγγραφείς
Voutsinas, G. E.
Stavrou, E. F.
Karousos, G.
Dasoula, A.
Papachatzopoulou, A.
Syrrou, M.
Verkerk, A. J.
van der Spek, P.
Patrinos, G. P.
Stoger, R.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
Hum Mutat
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
Genetic alterations in the alpha-synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady-state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild-type-allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis.
Περιγραφή
Λέξεις-κλειδιά
Alleles, *Allelic Imbalance, Amino Acid Substitution, Cell Line, Transformed, Epigenesis, Genetic, Female, Gene Dosage, Gene Expression, Histones/metabolism, Humans, *Mutation, Parkinson Disease/*genetics/metabolism, Polymorphism, Single Nucleotide, Protein Processing, Post-Translational, Reverse Transcriptase Polymerase Chain Reaction, alpha-Synuclein/*genetics
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/20340137
http://onlinelibrary.wiley.com/store/10.1002/humu.21248/asset/21248_ftp.pdf?v=1&t=h0dic38x&s=0288d753d3b7355136c020b5bd72287cb11d4f1a
http://onlinelibrary.wiley.com/store/10.1002/humu.21248/asset/21248_ftp.pdf?v=1&t=h0dic38x&s=0288d753d3b7355136c020b5bd72287cb11d4f1a
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής