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https://ptsldigital.ukm.my/jspui/handle/123456789/500506Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Endom Ismail, Dr. | - |
| dc.contributor.author | Farahnaz Amini (P39390) | - |
| dc.date.accessioned | 2023-10-13T09:44:37Z | - |
| dc.date.available | 2023-10-13T09:44:37Z | - |
| dc.date.issued | 2012-06-14 | - |
| dc.identifier.other | ukmvital:121278 | - |
| dc.identifier.uri | https://ptsldigital.ukm.my/jspui/handle/123456789/500506 | - |
| dc.description | More than 180 different G6PD variants have been reported worldwide with each population exhibiting their own prevalence and molecular variants for the G6PD gene. The objective of the present study is to determine the prevalence and molecular basis of G6PD deficiency in the Negrito Orang Asli. Population screening was performed on 600 Negrito individuals in three Malaysian states of Kedah, Kelantan and Perak using the fluorescent spot test. The mean G6PD enzyme activity ranged from 0.86 – 6.37 IU/gHb in deficient individuals. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis on DNA samples from Negrito individuals showed that common mutations seen in three major ethnic groups in Malaysia, namely Malay, Chinese and Indian, and other Southeast Asians were not prevalent in the Negrito group. Exons 6, 9, 11, 12 and 13 were hot spots for G6PD variants in the Negrito, and a combination of silent mutation C1311T and intervening sequences 11 (IVS11) T93C was found to be the most common mutational features in the Negrito group (designated here as G6PD 1311/93). Consequently, blood was collected from 103 Negrito volunteers and 45 non-aboriginal individuals (Malay, Chinese and Indians). Outs of 103 Negrito individuals, 48 were G6PD deficient with 40 individuals carrying the G6PD 1311/93 variant (83.3%). G6PD 1311/93 was also identified in six individuals from the non-aboriginal group. Since genotype of G6PD 1311/93 does not explain the G6PD-deficient condition in the affected individuals, we sought to determine any change such as single nucleotide polymorphism (SNP) in the 3' untranslated region (3'UTR) of the G6PD gene. The entire 3'UTR of the G6PD gene in all Negrito and non-aboriginal samples were amplified and sequenced. Three novel SNPs, rs112950723 (+272 G/A), rs111485003 (+304 T/C) and rs1050757 (+357 A/G) were detected. rs1050757G, which is located inside an AG-rich region, showed a significant association with G6PD 1311/93 as it was present solely in all individuals with G6PD 1311/93. Therefore, in this study, various bioinformatic approaches were implemented to explain relationship between G6PD deficiency with haplotype 1311T/ 93C/rs1050757G. It was found that five microRNAs (miRNA) have the potential to bind to the 3'UTR of mutant mRNA; two of these bind to the regions encompassing SNP rs1050757. Consequently, significant alteration was observed in the secondary structure of mutant mRNA which led to different stem-loop and internal loop structures. The presence of rs1050757G appears to result in the translational repression of G6PD mRNA and subsequent loss of G6PD production. Conclusively, the frequency of G6PD deficiency in the Negrito is the highest in Malaysia. G6PD 1311/93/ rs1050757G is the predominant variation in the G6PD gene within the Negrito (83.3%) which is the world's highest frequency for this variant. The data suggests that the Negrito is a homogenous population with respect to the G6PD gene. This is the first report on the clinical role of an SNP in 3'UTR of G6PD mRNA and its direct association with human G6PD deficiency.,'Certification of Masters/Doctorial Thesis' is not available,Ph.D | - |
| dc.language.iso | eng | - |
| dc.publisher | UKM, Bangi | - |
| dc.relation | Faculty of Science and Technology / Fakulti Sains dan Teknologi | - |
| dc.rights | UKM | - |
| dc.subject | Dissertations, Academic -- Malaysia | - |
| dc.subject | Glucose-6-phosphatase | - |
| dc.subject | Dehydrogenases | - |
| dc.subject | Glucose-6-phosphate dehydrogenase | - |
| dc.subject | Indigenous peoples -- Malaysia | - |
| dc.title | Biochemical and genetic study of glucose-6-phosphate-dehydrogenase in the Malaysian Negrito orang asli | - |
| dc.type | Theses | - |
| dc.format.pages | 175 | - |
| dc.identifier.callno | QP603.G57F345 2012 tesis | - |
| dc.identifier.barcode | 003060 (2012) | - |
| Appears in Collections: | Faculty of Science and Technology / Fakulti Sains dan Teknologi | |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| ukmvital_121278+SOURCE1+SOURCE1.0.PDF Restricted Access | 43.22 MB | Adobe PDF |  View/Open |
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