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Fulltext Genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers coinherited with -α3.7 deletion

Lim, L. N., Yu, K. S., Chua, S. M., George, E., Lai, M. I., Wong, L., et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):47-47.
MyJurnal

Introduction: Filipino β°-deletion is predominant among the β-thalassaemia patients in the indigenous population of Sabah, Malaysia particularly among the Kadazandusun. Individuals who co-inherit with α- and β-thalassaemia will demonstrate milder clinical symptoms with modified complete blood count (CBC) and Hb subtype parameters. HBS1L-MYB variants act as one of the key regulator of haematopoiesis and erythropoiesis and display strong association
with variation of HbF levels. Therefore, this study aims to evaluate the association between genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers co-inherited with -α3.7 deletion. Methods: Filipino β°-deletion and -α3.7 deletion were identified using gap-polymerase chain reaction (PCR). A total of 34 subjects found with coinheritance of Filipino β°-deletion and -α3.7 deletion were subjected for HBS1L-MYB intergenic polymorphisms (HMIP) analysis. Hb subtypes level were quantified using BioRad Variant II Hb analyser. Genotyping of HBS1L-MYB variants rs9399137 and rs11759553 was done using own designed tetra primer ARMS-PCR. Results: The minor allele frequencies (MAF) of the two HMIP is found more than 0.05 (rs11759553, MAF=0.18 and rs9399137, MAF=0.15), indicating the significance of these variants among the study subjects. Significant difference was found between HbF level and HBS1L-MYB variant rs11759553 with p-value less than 0.05 (p=0.001). Subjects with homozygous genotype for rs11759553 (T/T) was found with higher HbF, followed by heterozygous (A/T) and wild type (A/A). rs11759553 and rs9399137 was found did not influence the level of HbA and HbA2. HMIP of rs11759553 and rs9399137 are found significant among Filipino β°-deletion carriers co-inherited with -α3.7deletion with its high minor allelic frequency and high HbF level. Strong association with HbF level was demonstrated when
coinheritance of rs11759553. Conclusion: This study demonstrates that there are significant associations between certain genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers co-inherited with -α3.7 deletion.
Fulltext Induced pluripotent stem cells: history, properties and potential applications

Nordin N, Lai MI, Veerakumarasivam A, Ramasamy R, Abdullah S, Wendy-Yeo WY, et al.

Med J Malaysia, 2011 Mar;66(1):4-9.
PMID: 23765134 MyJurnal

The development of induced pluripotent stem cells (iPSCs) has been met with much enthusiasm and hailed as a breakthrough discovery by the scientific and research communities amidst the divisive and ongoing debates surrounding human embryonic stem cells (hESC) research. The discovery reveals the fact that embryonic pluripotency can be generated from adult somatic cells by the induction of appropriate transcriptional factor genes essential for maintaining the pluripotency. They provide an alternative source for pluripotent stem cells, thus representing a powerful new research tool besides their potential application in the field of regenerative medicine. In this review, the historical background of iPSCs generation will be discussed together with their properties and characteristics as well as their potential therapeutic applications.
The use of Taqman genotyping assays for rapid confirmation of β-thalassaemia mutations in the Malays: accurate diagnosis with low DNA concentrations

Teh LK, Lee TY, Tan JA, Lai MI, George E

Int J Lab Hematol, 2015 Feb;37(1):79-89.
PMID: 24725998 DOI: 10.1111/ijlh.12240

In Malaysia, β-thalassaemia is a common inherited blood disorder in haemoglobin synthesis with a carrier rate of 4.5%. Currently, PCR-incorporating techniques such as amplification refractory mutation system (ARMS) or reverse dot blot hybridization (RDBH) are used in β-thalassaemia mutation detection. ARMS allows single-mutation identification using two reactions, one for wild type and another for mutant alleles. RDBH requires probe immobilization and optimization of hybridization and washing temperatures which is time consuming. The aim of our study was to investigate whether β-thalassaemia mutations can be identified in samples with low DNA concentrations.
An assessment of three noncommercial DNA extraction methods from dried blood spots for beta-thalassaemia mutation identification

Karthipan SN, George E, Jameela S, Lim WF, Teh LK, Lee TY, et al.

Int J Lab Hematol, 2011 Oct;33(5):540-4.
PMID: 21884505 DOI: 10.1111/j.1751-553X.2011.01304.x

Dried blood spots (DBS) are currently the recommended sample collection method for newborn screening programmes in America. Early diagnosis of beta-thalassaemia screening is essential as it provides an added advantage especially in sickle cell disease. Beta-thalassaemia frequency is high in many poor countries, and the cost of using commercial DNA extraction kits can be prohibitive. Our study assessed three methods that use minimal reagents and materials to extract DNA from DBS for beta-thalassaemia identification.
Rapid detection of α-thalassaemia variants using droplet digital PCR

Lee TY, Lai MI, Ramachandran V, Tan JA, Teh LK, Othman R, et al.

Int J Lab Hematol, 2016 Aug;38(4):435-43.
PMID: 27349818 DOI: 10.1111/ijlh.12520

INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately.
METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR).
RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously.
CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.
Fulltext Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia

Lee TY, Lai MI, Ismail P, Ramachandran V, Tan JA, Teh LK, et al.

Genet. Mol. Res., 2016 Apr 07;15(2).
PMID: 27173219 DOI: 10.4238/gmr.15027400

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.