Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/29908
Title: Nonsense mediated decay in Beta-Thalassemia
Authors: LOO POOI ENG
Keywords: nonsense mediated decay
Issue Date: 24-Dec-2009
Source: LOO POOI ENG (2009-12-24). Nonsense mediated decay in Beta-Thalassemia. ScholarBank@NUS Repository.
Abstract: ?-thalassemia is one of the most common single gene disorders that results from reduced or non-production of ?-globin chains. Most of the ?-thalassemias are caused by frameshift or nonsense mutations within the ?-globin gene or its immediate flanking sequences, which produce premature termination codons (PTCs). In ?- thalassemia, nonsense mediated decay (NMD) offers protection from the potentially deleterious effects of PTCs, which will result in the synthesis of truncated proteins. Hence, the relationship between NMD with the location of PTCs in ?-thalassemia was studied by analyzing the gene expression levels of codon 41/42 mutations (-TTCT) (located at exon 2), codon 121 mutations (G?T) (located at exon 3) and IVS 2-654 mutations (C?T) (located at intron 2). Steady state gene expression study in HeLa cells showed to comply with the 50-55 nucleotide boundary rule of NMD. The observation was confirmed by using a transcriptional pulse-chase strategy, HeLa Tet- Off system. Gene expression study in MEL (mouse erythroleukemia) cells showed similar results except for IVS 2-654 mutation, whereby a relatively low gene expression level was observed. This interesting observation suggests that the 50-55 nucleotide boundary rule does not apply to IVS 2-654 and we postulated that the extra 73 nucleotides intronic sequences in IVS 2-654 mutant transcript is able to trigger NMD and subsequently contributed to the recessive inheritance phenotype of the mutation.
URI: http://scholarbank.nus.edu.sg/handle/10635/29908
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