The human leukaemia develops with abnormal increase of blast cells in the bone marrow. Leukaemia is caused by genetic aberrations which activates proto-oncogenes and inactivates tumor-suppressor genes and eventually leads to leukemogenesis. Myelodysplastic syndrome is a preleukemic state which shares similar symptoms and causative factors as leukaemia. FOXO3 and c-Myc have been increasingly recognized as key regulatory genes involved in the initiation and development of leukaemia and myelodysplastic syndromes. Their roles in these diseases is being investigated and findings thus far has indicated that FOXO3 acts as a tumor suppressor while c-Myc has been identified as a proto-oncogene. Currently published literature indicate that there are limited research on the correlation between FOXO3 and c-Myc especially in leukaemia and myelodysplastic syndrome. This review will focus on the key regulatory roles of FOXO3 and c-Myc in leukaemia and myelodysplastic syndrome.
Colorectal cancer (CRC) is one of the most common cancer worldwide with approximately 2 to 5% of all colon cancers are associated with well-defined hereditary factors. Hereditary nonpolyposis colorectal cancer (Hereditary Nonpolyposis Colorectal Cancer), also known as Lynch syndrome (LS), is the most common form of hereditary CRC characterized by an early age of onset and follows the autosomal dominant inheritance pattern. HNPCC is caused by the alteration in four mismatch repair (MMR) genes. Immunohistochemistry (IHC) and microsatellite instability (MSI) testing, followed by conventional Sanger sequencing reliably identify the majority of mutations. However, methods to identify other underlying variants or genomic rearrangements of HNPCC have emerged. In addition to the clinical characterization and evaluation of HNPCC patients, the implementation of screening strategies for both affected and unaffected CRC patients together with the accelerated advancement in molecular testing methods will shed light on a more comprehensive detection of HNPCC. In this review, the approaches for the selection of high-risk HNPCC and molecular testing performed over the past few years are discussed.
The rapid progression of molecular-based technology now enables us to analyse huge number of samples. Nonetheless, DNA (Deoxyrebonucleic acid) extraction is always a limiting factor. In this study, we analysed human microbes to compare the performance of DNA extraction methods: simple boiling method and MasterPureTM Complete DNA and RNA Purification Kit. Dental plaque was initially collected from 12 subjects, 6 of which were from individuals with caries active lesions with International Caries Detection and Assessment System (ICDAS) score five and six, and 6 samples from non-caries subjects, were collected in deionised water. The bacterial samples were extracted by the two aforementioned methods and examined using gel electrophoresis, followed by polymerase chain reaction (PCR). Streptococcus mutans was detected using conventional polymerase chain reaction (PCR). Our results demonstrated that boiling method produced higher DNA concentration (100 – 350 ng/µl), however, the commercial kit yield superior in DNA quality with single and specific PCR products. Based on the findings, the commercial kit is the better choice and practicable method for DNA extraction considering the quality of the DNA yield.
Introduction: Exome sequencing technology which is part of Next Generation Sequencing (NGS) is known for detection of various disease mutations through commercially available platforms. Less reports in identifying genetic variation in non-syndromic cleft lip with or without cleft palate (NSCL/P) in Malaysia had embarked for discovery of susceptible genes to fill in the gaps with the healthcare delivery for a better treatment and management to the patients and family. Methods: Whole exome sequencing was carried out on two Malay NSCLP patients. Blood samples were withdrawn and intact DNA was extracted, fragmented, purified and hybridized using exome sequencing capture and sequenced with Agilent 2100 Bioanalyzer platform. Bioinformatic analyses were done and reviewed with GenBank and PubMed database. Variants were filtered based upon a high impact variant. Results: We have identified single nucleotide polymorphisms in 2 genes (PDE4DIP and PDE11A) and InDels frameshift mutations in 4 genes (PDE4DIP, LTBP4, MMP12 and MMP28). Our preliminary study presents the successful application of whole exome sequencing to elucidate the genetic basis of NSCLP in Malays. Conclusion: Mutations that have been identified would shed more light on the susceptible genes to non-syndromic clefts and further investigation shall be carried out to confirm.
Introduction: The Pro12Ala variant of the Peroxisome Proliferator Activated Receptor Gamma (PPARγ) is one of the critical genetic factor predispose to positive energy balance leading to obesity. Objective: This study aimed to determine the association between Pro12Ala variant in the PPARγ gene with body mass index (BMI) status, physical activity and fat intake among Malay children. Methods: A total of 119 participants aged between 9-11 years old from primary schools in Kota Bharu, Kelantan were recruited. Anthropometric measurements were taken and activity counts of the participants were recorded using accelerometer (Actigraph GT3X+). A food diary was distributed to all participants to collect the data of their fat intake. Genotyping was performed using High Resolution Melting (HRM) analysis. Data obtained were analysed using SPSS version 19. Results: There was a significant association between Pro12Ala variant in the PPARγ gene with BMI status. The allelic frequency of wildtype (Ala/ala) and heterozygous (Pro/ala) among overweight group were 0.83 and 0.17 respectively and 0.92 and 0.08 in the normal weight group (p=0.03). There was a significant difference in BMI, waist circumference and hip circumference between heterozygous and wildtype groups. Conclusion: The study found that there was a significant role of Pro12Ala variant in the PPARγ gene in overweight Malay children.