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Identifier uch.med.msc//2005tsagkaraki
Title Μοριακή μελέτη της χρωμοσωμικής περιοχής 15q11-q13 Μελέτη του προτύπου μεθυλίωσης Μελέτη μεταλλάξεων στο γονίδιο UBE3A
Creator Tsagkaraki, Eumorfia
Abstract In mammals, both parents contribute equal genetic information to their offspring. Most autosomal genes will be expressed from both the maternal and paternal alleles. Instead, there is a group of genes that are expressed from only one of the two alleles in a parent-of-origin-dependent manner. These genes are designated as imprinted since they retain the parental identity they acquired during gametogenesis. Major role in imprinting procedure plays the methylation of DNA.Deviation from appropriate parent-of-origin-dependent expression may have dire consequences for the organism (Mellissa et al, 1999). The Prader-Willi (PWS) and Angelman (AS) syndromes are clinically dinstict development and neurobehavioural entities that result from the loss of imprinted gene expression within chromosome region 15q11-q13: deletions on the paternal chromosome cause PWS, whereas those on the maternal chromosome cause AS. The molecular mechanisms responsible for the loss of imprinted gene expression in 15q11-q13 region are quite similar for the two syndromes, including large deletions (70% of Prader Willi patients and 65- 70% of Angelman patients), uniparental disomy (maternal uniparental disomy 15 in 25-30% of Prader Willi patients and paternal uniparental disomy 15 in 1-3% of Angelman patients), and rare chromosomal rearrangements (< 1% in Prader Willi and Angelman syndrome patients). Lately, mutations in the UBE3A gene have been found and have been correlated with the clinical manifestations of Angelman syndrome. Such mutations concerning Prader Willi have not been reported. Molecular diagnosis of the two syndromes includes the study of dinucleotide repeat polumophisms (DNRPs)- method that determines large deletions and uniparental disomy- , the detection of chromosomal rearrangements and small deletions using FISH method (Fluoresence in situ hybridization), and the study of methylation imprinting pattern using the bisylfite DNA modification method followed by methylation specific PCR (MSPCR). Molecular analysis of the two syndromes has revealed that MSPCR can detect the whole of the Prader Willi cases and 80% of Angelman syndrome cases, while it can provide safe molecular diagnosis for the cases where the other molecular methods cannot. In the present study, we identified a base substitution in intron 12 of the UBE3A gene in one Angelman syndrome patient, with no deletion, no UPD or chromosomal rearrangements. The substitution is a T to G change, IVS2650- 13T> G, and results in the formation of a possible new donor splice site. According to the bibliography, such mutations have been found in several genes and result in the formation of an abnormal mRNA, which can lead to the production of a non- functional protein product (Antonarakis S. and Cooper D.) Further analysis of this substitution should be performed in order to exclude the possibility of a genetic polymorphism; additional expression studies would provide information on the protein product of this mutated gene, its function, and its possible relation to the Angelman syndrome phenotype.
Issue date 2005-12-01
Date available 2006-10-20
Collection   Faculty/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/f/b/5/metadata-dlib-2005tsagkaraki.tkl Bookmark and Share
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