Title Genetic polymorphisms in mitochondrial DNA hypervariable regions I, II and III of the Malaysian population Author Genetic polymorphisms in mitochondrial DNA hypervariable regions I, II and III of the Malaysian population

Abstract. Nucleotide sequence variabilities in the three hypervariable (HV-) regions, HV1, HV2, and HV3, of the noncoding control region of human mitochondrial DNA (mtDNA) from a portion of the Malaysian population were elucidated with the use of polymerase chain reaction (PCR) appropriate gel detection and flourescence based sequencing methodologies. Genomic DNA were extracted from 195 randomly selected individuals (15 samples from each of the 13 ethnicities ranging from of Malay, Chinese, Indian, Punjabi, indigenous Sarawakian, indigenous Sabahan, and Orang Asli ) and nucleotide sequence variabilities in HV1, HV2, and HV3 regions, were determined. These were located in the control region that contains sequences responsible for transcription and replication control of the mtDNA. The control region is located between the tRNA genes that encoded proline and phenylalanine, respectively. We found that the noncoding segments of the control region were polymorphic in the Malaysian samples. The polymorphisms within the control region exhibited a significant degree of diversity, thus enabling the three HV-regions of the control region of mtDNA to be used as additional markers in individual identification in forensic investigations, supplementing nuclear DNA markers. The results generated could also further complement anthropology and population studies in Asia

A simple instrument for the assessment of student performance in problem-based learning tutorials.

INTRODUCTION: A process-oriented instrument was developed for the summative assessment of student performance during problem-based learning (PBL) tutorials. This study evaluated (1) the acceptability of the instrument by tutors and (2) the consistency of assessment scores by different raters. MATERIALS AND METHODS: A survey of the tutors who had used the instrument was conducted to determine whether the assessment instrument or form was user-friendly. The 4 competencies assessed, using a 5-point rating scale, were (1) participation and communication skills, (2) cooperation or team-building skills, (3) comprehension or reasoning skills and (4) knowledge or information-gathering skills. Tutors were given a set of criteria guidelines for scoring the students' performance in these 4 competencies. Tutors were not attached to a particular PBL group, but took turns to facilitate different groups on different case or problem discussions. Assessment scores for one cohort of undergraduate medical students in their respective PBL groups in Year I (2003/2004) and Year II (2004/2005) were analysed. The consistency of scores was analysed using intraclass correlation. RESULTS: The majority of the tutors surveyed expressed no difficulty in using the instrument and agreed that it helped them assess the students fairly. Analysis of the scores obtained for the above cohort indicated that the different raters were relatively consistent in their assessment of student performance, despite a small number consistently showing either "strict" or "indiscriminate" rating practice. CONCLUSION: The instrument designed for the assessment of student performance in the PBL tutorial classroom setting is user-friendly and is reliable when used judiciously with the criteria guidelines provided

Students perception and acceptance of problem-based learning (PBL) in a hybrid traditional-PBL curriculum

Even though there are several variants in its implementation, problem-based learning (PBL) is essentially a form of student-centred learning that involves enquiry-based discussion triggered by a problem and facilitated by a tutor in small groups. In a hybrid traditional-PBL curriculum where PBL runs parallel with conventional didactic teaching, there is always a concern that such curricular arrangement may produce undesirable learning behaviour. Therefore, this paper evaluated the students' perception and acceptance of PBL in such a learning environment. PBL was introduced in a gradual manner into the first three years of a revised undergraduate medical curriculum at the University of Malaya (UM) in 1999/2000. Self-administered questionnaires were distributed to students of Phases I, II (first two preclinical years) and IIIA (first of the three clinical years) after completing their respective final examination papers. The study compared the responses of at least nine cohorts of students (2001 to 2009) on questions related to PBL. Students were asked to respond to each question based on their own experience using a 5-point Likert scale. Across the board, progressively over the years, students from all the phases reported an improvement in their critical thinking, integration of knowledge, appreciation of understanding rather than merely memorising facts, communication skills, and braveness to counter-propose opinions. The effects were more obvious with Phase I students compared with students from the other two phases. Written comments from the students also showed a shift from resistance and outright call for the abolishment of PBL tutorials, to positive call to increase PBL tutorials

Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus in Three Main Ethnic Groups of the Malaysian Population

The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants

Evaluation of SLE Susceptibility Genes in Malaysians

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P<0.05). The strongest signal was at HLA-DRA (PMeta=9.96×10-9; PCH=6.57×10-8, PMA=6.73×10-3); the strongest non-HLA signal occurred at STAT4 (PMeta=1.67×10-7; PCH=2.88×10-6, PMA=2.99×10-3). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies

Association between inflammatory bowel disease gene 5 (IBD5) and interleukin‐23 receptor (IL23R) genetic polymorphisms in Malaysian patients with Crohn's disease

OBJECTIVE: This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a₁ (rs11739135), IGR2096a₁ (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population. METHODS: Blood samples from 80 CD patients and 100 healthy controls were recruited. Genomic DNA was extracted and analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The results revealed that there was an increased frequency of IGR2198a₁ C allele (8.8 in CD, 1.5 in controls, P < 0.05, OR 6.30, 95 CI 1.7722.31) and IGR2096a₁ T allele (6.9 in CD, 1.5 in controls, P < 0.05, OR 4.85, 95 CI 1.3317.69) in the CD patients as compared to the controls, suggesting the two variants were potential risk factors of CD. Both risk alleles (C and T) were highest in Indians. In contrast, no significant difference was observed for the IL23R gene variant (rs1004819) between these two groups (P = 0.941). All genotypes and alleles of this gene variant were present in equal ratios in the CD and control groups (OR 1.02, 95 CI 0.661.57 for T allele and OR 0.98, 95 CI 0.641.52 for C allele). CONCLUSIONS: There is a strong association between both IBD5 locus variants but not the IL23R gene variant with CD in the Malaysian population. The IBD5 locus variants were highest in Indians, which may explain the increased susceptibility of this particular ethnic group to the disease

Polymorphisms in methylenetetrahydrofolate reductase gene and risk of non-Hodgkin lymphoma in a multi-ethnic population

An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P ¼ 0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P ¼ 0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P ¼ 0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL