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  1. Sequence and phylogenetic analysis of the VP2 gene of very virulent infectious bursal disease virus isolates
    Hoque MM, Omar AR, Hair-Bejo M, Aini I
    J. Biochem. Mol. Biol. Biophys., 2002 Apr;6(2):93-9.
    PMID: 12186763
    Previously we have shown that very virulent infectious bursal disease viruses (vvIBDV) that are SspI, TaqI and StyI positive (92/04, 97/61 and 94/B551) but not SspI and TaqI positive and StyI negative (94/273) cause high mortality, up to 80% in specific-pathogen-free chickens with significant damage of the bursal as well as nonbursal tissues. In this study, we sequenced the VP2 gene (1351 bp) of the 92/04, 94/273 and 94/B551 and compared them with other IBDV strains. All the isolates have the unique amino acid residues at positions 222A, 256I, 294I and 299S found in other vvIBDV strains. The deduced VP2 amino acids encoded by 92/04 is identical to the vvIBDV strains from Israel (IBDVKS), Japan (OKYM) and Europe (UK661), whereas the 94/273 and 94/B551 isolates have one to three amino acid substitutions. The 94/273 has two amino acid substitutions at positions 254 G to S and at 270 A to E that have not been reported before from vvIBDV strains. The 94/B551 also has one amino acid substitution at position 300 E to S, which is uncommon among other vvIBDV strains. However, phylogenetic analysis suggested that the isolates are very close to each other and all of them may have derived from the same origin as vvIBDV strains isolated from China, Japan and Europe. Even though antigenic index analysis of the 94/273 and 94/B551 indicated that the isolates are unique compared to other IBDV strains, their antigenic variation remain to be determined by monoclonal antibody study.
    Matched MeSH terms: Antigens, Viral/genetics; DNA, Viral/genetics; Infectious bursal disease virus/genetics*; Virulence/genetics; Viral Structural Proteins/genetics*
  2. Human Fc gamma receptor IIA (FcgammaRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia
    Yap SN, Phipps ME, Manivasagar M, Tan SY, Bosco JJ
    Lupus, 1999;8(4):305-10.
    PMID: 10413210 DOI: 10.1191/096120399678847876
    SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.
    Matched MeSH terms: Lupus Erythematosus, Systemic/genetics*; Lupus Nephritis/genetics; Antigens, CD/genetics*; Receptors, IgG/genetics*; Asian Continental Ancestry Group/genetics
  3. Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays
    Zhao B, Lee EJ, Wong JY, Yeoh PN, Gong NH
    Pharmacogenetics, 1995 Oct;5(5):275-80.
    PMID: 8563767
    Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.
    Matched MeSH terms: Arylamine N-Acetyltransferase/genetics*; Cytochrome P-450 Enzyme System/genetics*; Glutathione Transferase/genetics*; Isoenzymes/genetics; Asian Continental Ancestry Group/genetics*
  4. HLA-DRB genes and antiribosomal P antibodies in systemic lupus erythematosus
    Teh LS, Doherty DG, Williams BD
    Br J Rheumatol, 1994 Dec;33(12):1125-6.
    PMID: 8000739
    Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese.
    Matched MeSH terms: Complement C4/genetics; HLA-DQ Antigens/genetics; HLA-DR Antigens/genetics*; Lupus Erythematosus, Systemic/genetics*; Asian Continental Ancestry Group/genetics
  5. Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia
    Tarone RE, Levine PH, Yadav M, Pandey JP
    Cancer Res, 1990 Jun 1;50(11):3186-8.
    PMID: 1692255
    The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
    Matched MeSH terms: Epitopes/genetics*; Haplotypes/genetics*; Immunoglobulin gamma-Chains/genetics*; Immunoglobulin Heavy Chains/genetics*; Immunoglobulin kappa-Chains/genetics*
  6. A PCR-based sex determination method for possible application in caprine gender selection by simultaneous amplification of the Sry and Aml-X genes
    Phua AC, Abdullah RB, Mohamed Z
    J. Reprod. Dev., 2003 Aug;49(4):307-11.
    PMID: 14967923
    Sex determination of livestock is performed to achieve the objectives of livestock breeding programmes. Techniques for sex determination have evolved from karyotyping to detecting Y-specific antigens and recently to the polymerase chain reaction (PCR), which appears to be the most sensitive, accurate, rapid and reliable method to date. In this study, a PCR-based sex determination method for potential application in goat breeding programmes was developed. Primers were designed to amplify a portion of the X amelogenin gene (Aml-X) on the X chromosome to give a 300 bp product and Sry gene on the Y chromosome to give a 116 bp product. PCR optimization was performed using DNA template extracted from a whole blood sample of Jermasia goats (German Fawn x Katjang) of both sexes. It was possible to identify the sex chromosomes by amplifying both male- and female-specific genes simultaneously in a duplex reaction with males yielding two bands and females yielding one band. The Aml-X primer set, which served as an internal control primer, did not interfere with amplification of the Y-specific sequence even when a low amount of DNA (1 ng) was used. The duplex reaction subjected to a blind test showed 100% (14/14) concordance, proving its accuracy and reliability. The primer sets used were found to be highly specific and were suitable for gender selection of goats.
    Matched MeSH terms: Dental Enamel Proteins/genetics; Goats/genetics*; X Chromosome/genetics; Y Chromosome/genetics; DNA Primers/genetics
  7. Recombinant expression of the larval excretory-secretory antigen TES-120 of Toxocara canis in the methylotrophic yeast Pichia pastoris
    Fong MY, Lau YL
    Parasitol Res, 2004 Jan;92(2):173-6.
    PMID: 14655048
    A gene encoding the larval excretory-secretory antigen TES-120 of the dog ascarid worm Toxocara canis was cloned into the methylotrophic yeast Pichia pastoris. Specificity of the recombinant TES-120 antigen produced by the yeast was investigated. Forty-five human serum samples from patients infected with different()parasitic organisms, including 8 cases of toxocariasis, were tested against the recombinant antigen in immunoblot assays. Results from the assays showed that the recombinant TES-120 antigen reacted with sera from toxocariasis patients only. This highly specific recombinant TES-120 antigen can potentially be used for the development of an inexpensive serodiagnostic assay for human toxocariasis.
    Matched MeSH terms: Antigens, Helminth/genetics; Larva/genetics; Pichia/genetics; Recombinant Proteins/genetics; Toxocara canis/genetics
  8. Fulltext Ion channels, long QT syndrome and arrhythmogenesis in ageing
    Jeevaratnam K, Chadda KR, Salvage SC, Valli H, Ahmad S, Grace AA, et al.
    Clin Exp Pharmacol Physiol, 2017 12;44 Suppl 1:38-45.
    PMID: 28024120 DOI: 10.1111/1440-1681.12721
    Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.
    Matched MeSH terms: Action Potentials/genetics*; Aging/genetics*; Heart Rate/genetics*; Long QT Syndrome/genetics*; NAV1.5 Voltage-Gated Sodium Channel/genetics*
  9. Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction
    Naidu R, Wahab NA, Yadav M, Kutty MK
    Int J Mol Med, 2002 Feb;9(2):189-96.
    PMID: 11786932
    Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
    Matched MeSH terms: Aging/genetics; Breast Neoplasms/genetics*; Neoplasm Invasiveness/genetics; Genes, myc/genetics*; Proto-Oncogene Proteins c-myc/genetics
  10. Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes
    Tan JA, Tan KL, Omar KZ, Chan LL, Wee YC, George E
    Eur J Pediatr, 2009 Sep;168(9):1049-54.
    PMID: 19034506 DOI: 10.1007/s00431-008-0877-9
    INTRODUCTION: Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A).

    MATERIALS AND METHODS: HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia.

    RESULTS AND DISCUSSION: Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA.

    CONCLUSION: The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.

    Matched MeSH terms: Codon/genetics*; Hemoglobins, Abnormal/genetics*; beta-Thalassemia/genetics*; Point Mutation/genetics*; DNA Primers/genetics
  11. Cold-adapted RTX lipase from antarctic Pseudomonas sp. strain AMS8: isolation, molecular modeling and heterologous expression
    Ali MS, Ganasen M, Rahman RN, Chor AL, Salleh AB, Basri M
    Protein J, 2013 Apr;32(4):317-25.
    PMID: 23645400 DOI: 10.1007/s10930-013-9488-z
    A new strain of psychrophilic bacteria (designated strain AMS8) from Antarctic soil was screened for extracellular lipolytic activity and further analyzed using molecular approach. Analysis of 16S rDNA showed that strain AMS8 was similar to Pseudomonas sp. A lipase gene named lipAMS8 was successfully isolated from strain AMS8, cloned, sequenced and overexpressed in Escherichia coli. Sequence analysis revealed that lipAMS8 consist of 1,431 bp nucleotides that encoded a polypeptide consisting of 476 amino acids. It lacked an N-terminal signal peptide and contained a glycine- and aspartate-rich nonapeptide sequence at the C-terminus, which are known to be the characteristics of repeats-in-toxin bacterial lipases. Furthermore, the substrate binding site of lipAMS8 was identified as S(207), D(255) and H(313), based on homology modeling and multiple sequence alignment. Crude lipase exhibited maximum activity at 20 °C and retained almost 50 % of its activity at 10 °C. The molecular weight of lipAMS8 was estimated to be 50 kDa via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal expression level was attained using the recombinant plasmid pET32b/BL21(DE3) expressed at 15 °C for 8 h, induced by 0.1 mM isopropyl β-D thiogalactoside (IPTG) at E. coli growth optimal density of 0.5.
    Matched MeSH terms: Bacterial Proteins/genetics; Escherichia coli/genetics; Lipase/genetics; Pseudomonas/genetics; Recombinant Proteins/genetics
  12. Fulltext Viral Fitness Landscapes in Diverse Host Species Reveal Multiple Evolutionary Lines for the NS1 Gene of Influenza A Viruses
    Muñoz-Moreno R, Martínez-Romero C, Blanco-Melo D, Forst CV, Nachbagauer R, Benitez AA, et al.
    Cell Rep, 2019 12 17;29(12):3997-4009.e5.
    PMID: 31851929 DOI: 10.1016/j.celrep.2019.11.070
    Influenza A viruses (IAVs) have a remarkable tropism in their ability to circulate in both mammalian and avian species. The IAV NS1 protein is a multifunctional virulence factor that inhibits the type I interferon host response through a myriad of mechanisms. How NS1 has evolved to enable this remarkable property across species and its specific impact in the overall replication, pathogenicity, and host preference remain unknown. Here we analyze the NS1 evolutionary landscape and host tropism using a barcoded library of recombinant IAVs. Results show a surprisingly great variety of NS1 phenotypes according to their ability to replicate in different hosts. The IAV NS1 genes appear to have taken diverse and random evolutionary pathways within their multiple phylogenetic lineages. In summary, the high evolutionary plasticity of this viral protein underscores the ability of IAVs to adapt to multiple hosts and aids in our understanding of its global prevalence.
    Matched MeSH terms: Orthomyxoviridae Infections/genetics; Influenza A virus/genetics; Viral Nonstructural Proteins/genetics; Host-Pathogen Interactions/genetics*; Host Specificity/genetics*
  13. Comparison of culture-independent and dependent approaches for identification of native arsenic-resistant bacteria and their potential use for arsenic bioremediation
    Hamood Altowayti WA, Almoalemi H, Shahir S, Othman N
    Ecotoxicol Environ Saf, 2020 Dec 01;205:111267.
    PMID: 32992213 DOI: 10.1016/j.ecoenv.2020.111267
    Arsenic is a common contaminant in gold mine soil and tailings. Microbes present an opportunity for bio-treatment of arsenic, since it is a sustainable and cost-effective approach to remove arsenic from water. However, the development of existing bio-treatment approaches depends on isolation of arsenic-resistant microbes from arsenic contaminated samples. Microbial cultures are commonly used in bio-treatment; however, it is not established whether the structure of the cultured isolates resembles the native microbial community from arsenic-contaminated soil. In this milieu, a culture-independent approach using Illumina sequencing technology was used to profile the microbial community in situ. This was coupled with a culture-dependent technique, that is, isolation using two different growth media, to analyse the microbial population in arsenic laden tailing dam sludge based on the culture-independent sequencing approach, 4 phyla and 8 genera were identified in a sample from the arsenic-rich gold mine. Firmicutes (92.23%) was the dominant phylum, followed by Proteobacteria (3.21%), Actinobacteria (2.41%), and Bacteroidetes (1.49%). The identified genera included Staphylococcus (89.8%), Pseudomonas (1.25), Corynebacterium (0.82), Prevotella (0.54%), Megamonas (0.38%) and Sphingomonas (0.36%). The Shannon index value (3.05) and Simpson index value (0.1661) indicated low diversity in arsenic laden tailing. The culture dependent method exposed significant similarities with culture independent methods at the phylum level with Firmicutes, Proteobacteria and Actinobacteria, being common, and Firmicutes was the dominant phylum whereas, at the genus level, only Pseudomonas was presented by both methods. It showed high similarities between culture independent and dependent methods at the phylum level and large differences at the genus level, highlighting the complementarity between the two methods for identification of the native population bacteria in arsenic-rich mine. As a result, the present study can be a resource on microbes for bio-treatment of arsenic in mining waste.
    Matched MeSH terms: Firmicutes/genetics; RNA, Ribosomal, 16S/genetics; Proteobacteria/genetics; Actinobacteria/genetics; Microbiota/genetics
  14. Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing
    Ng PS, Wen WX, Fadlullah MZ, Yoon SY, Lee SY, Thong MK, et al.
    Clin Genet, 2016 10;90(4):315-23.
    PMID: 26757417 DOI: 10.1111/cge.12735
    Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
    Matched MeSH terms: Breast Neoplasms/genetics*; BRCA1 Protein/genetics; BRCA2 Protein/genetics; Tumor Suppressor Proteins/genetics; Ubiquitin-Protein Ligases/genetics
  15. Fulltext Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer's disease, Parkinson's disease
    Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.
    Biomed Pharmacother, 2019 Mar;111:765-777.
    PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101
    Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.
    Matched MeSH terms: Aging/genetics; Alzheimer Disease/genetics; Mitochondria/genetics; Parkinson Disease/genetics; Neurodegenerative Diseases/genetics
  16. Genetic characterization of Escherichia coli O157: H7/- strains carrying the stx2 gene but not producing Shiga toxin 2
    Koitabashi T, Vuddhakul V, Radu S, Morigaki T, Asai N, Nakaguchi Y, et al.
    Microbiol. Immunol., 2006;50(2):135-48.
    PMID: 16490932
    Nine Escherichia coli O157: H7/- strains isolated primarily from non-clinical sources in Thailand and Japan carried the stx(2) gene but did not produce Stx2 toxin in a reversed passive latex agglutination (RPLA) assay. A strain (EDL933) bearing a stx(2) phage (933W) was compared to a strain (Thai-12) that was Stx2-negative but contained the stx(2) gene. To study the lack of Stx2 production, the Thai-12 stx(2) gene and its upstream nucleotide sequence were analyzed. The Thai-12 stx(2) coding region was intact and Stx2 was expressed from a cloned stx(2) gene using a plasmid vector and detected using RPLA. A lacZ fusion analysis found the Thai-12 stx(2) promoter non-functional. Because the stx(2) gene is downstream of the late promoter in the stx(2) phage genome, the antitermination activity of Q protein is essential for strong stx(2) transcription. Thai-12 had the q gene highly homologous to that of Phi21 phage but not to the 933W phage. High-level expression of exogenous q genes demonstrated Q antitermination activity was weak in Thai-12. Replication of stx(2) phage was not observed in Stx2-negative strains. The q-stx(2) gene sequence of Thai-12 was well conserved in all Stx2-negative strains. A PCR assay to detect the Thai-12 q-stx(2) sequence demonstrated that 30% of O157 strains from marketed Malaysian beef carried this sequence and they produced little or no Stx2. These results suggest that stx(2)-positive O157 strains that produce little or no Stx2 may be widely distributed in the Asian environment.
    Matched MeSH terms: DNA, Bacterial/genetics; Bacteriophage lambda/genetics; Viral Proteins/genetics; Escherichia coli O157/genetics*; Shiga Toxin 2/genetics*
  17. Molecular characterization of a polymorphic 3-Mb deletion at chromosome Yp11.2 containing the AMELY locus in Singapore and Malaysia populations
    Yong RY, Gan LS, Chang YM, Yap EP
    Hum Genet, 2007 Nov;122(3-4):237-49.
    PMID: 17588179
    Amelogenin paralogs on Chromosome X (AMELX) and Y (AMELY) are commonly used sexing markers. Interstitial deletion of Yp involving the AMELY locus has previously been reported. The combined frequency of the AMELY null allele in Singapore and Malaysia populations is 2.7%, 0.6% in Indian and Malay ethnic groups respectively. It is absent among 541 Chinese screened. The null allele in this study belongs to 3 Y haplogroups; J2e1 (85.7%), F* (9.5%) and D* (4.8%). Low and high-resolution STS mapping, followed by sequence analysis of breakpoint junction confirmed a large deletion of 3 to 3.7-Mb located at the Yp11.2 region. Both breakpoints were located in TSPY repeat arrays, suggesting a non-allelic homologous recombination (NAHR) mechanism of deletion. All regional null samples shared identical breakpoint sequences according to their haplogroup affiliation, providing molecular evidence of a common ancestry origin for each haplogroup, and at least 3 independent deletion events recurred in history. The estimated ages based on Y-SNP and STR analysis were approximately 13.5 +/- 3.1 kyears and approximately 0.9 +/- 0.9 kyears for the J2e1 and F* mutations, respectively. A novel polymorphism G > A at Y-GATA-H4 locus in complete linkage disequilibrium with J2e1 null mutations is a more recent event. This work re-emphasizes the need to include other sexing markers for gender determination in certain regional populations. The frequency difference among global populations suggests it constitutes another structural variation locus of human chromosome Y. The breakpoint sequences provide further information to a better understanding of the NAHR mechanism and DNA rearrangements due to higher order genomic architecture.
    Matched MeSH terms: DNA/genetics; Cell Cycle Proteins/genetics; Chromosomes, Human, Y/genetics*; Asian Continental Ancestry Group/genetics; Amelogenin/genetics*
  18. Evaluation of in vitro cytochrome P450 induction and inhibition activity of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L
    Koe XF, Lim EL, Seah TC, Amanah A, Wahab HA, Adenan MI, et al.
    Food Chem Toxicol, 2013 Oct;60:98-108.
    PMID: 23876819 DOI: 10.1016/j.fct.2013.07.030
    Drug metabolism involving cytochrome P450 (CYP) enzymes is a key determinant of significant drug interactions. Deoxyelephantopin was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4, and protein expression and resultant enzymatic activity. The mRNA and protein expression of cytochrome isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis, respectively. Human CYP3A4 protein expression was determined using an optimized hCYP3A4-HepG2 cell-based assay and the enzymatic activity was evaluated using P450-Glo™ CYP3A4 assay. The molecular interaction and possible inhibition of deoxyelephantopin of the CYP3A4 enzyme was determined in silico and further validated using substrate-specific CYP3A4 inhibition assays. Deoxyelephantopin produced no significant effect on the CYP1A2 and CYP2D6 mRNA and protein expression. However, it has a weak induction effect on CYP3A4 at the transcriptional level. In silico docking simulation showed that deoxyelephantopin has a weak interaction with CYP3A4 enzyme and it minimally affects the metabolism of CYP3A4 substrates. Deoxyelephantopin is not an in vitro CYP1A2 and CYP2D6 inducer. It is both a weak in vitro CYP3A4 inducer and inhibitor and is unlikely to elicit a clinically significant effect in human.
    Matched MeSH terms: RNA, Messenger/genetics; Cytochrome P-450 CYP1A2/genetics; Cytochrome P-450 CYP2D6/genetics; Green Fluorescent Proteins/genetics; Cytochrome P-450 CYP3A/genetics
  19. Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese
    Yew PY, Mushiroda T, Kiyotani K, Govindasamy GK, Yap LF, Teo SH, et al.
    Mol Carcinog, 2012 Oct;51 Suppl 1:E74-82.
    PMID: 22213098 DOI: 10.1002/mc.21857
    Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2)  = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population.
    Matched MeSH terms: Glycoproteins/genetics*; Nasopharyngeal Neoplasms/genetics*; Phosphoproteins/genetics*; Proteins/genetics; Asian Continental Ancestry Group/genetics
  20. Fulltext Accumulation of Mitochondrial DNA Microsatellite Instability in Malaysian Patients with Primary Central Nervous System Tumors
    Radzak S, Khair Z, Ahmad F, Idris Z, Yusoff A
    Turk Neurosurg, 2021;31(1):99-106.
    PMID: 33491172 DOI: 10.5137/1019-5149.JTN.27893-20.4
    AIM: To determine the mitochondrial microsatellite instability (mtMSI) status in a series of Malaysian patients with brain tumors. Furthermore, we analyzed whether the mtMSI status is associated with the clinicopathological features of the patients.

    MATERIAL AND METHODS: Forty fresh frozen tumor tissues along with blood samples of brain tumor patients were analyzed for mtMSI by PCR amplification of genomic DNAs, and the amplicons were directly sequenced in both directions using Sanger sequencing.

    RESULTS: Microsatellite analysis revealed that 20% (8 out of 40) of the tumors were mtMSI positive with a total of 8 mtMSI changes. All mtMSI markers were detected in D310 and D16184 of the D-loop region. Additionally, no significant association was observed between mtMSI status and clinicopathological features.

    CONCLUSION: The variations, specifically the mtMSI, suggest that the mitochondrial DNA (mtDNA) can be targeted for genomic alteration in brain tumors. Therefore, the specific role of mtDNA alteration in brain tumor development and prognosis requires further investigation.

    Matched MeSH terms: Brain Neoplasms/genetics*; DNA, Mitochondrial/genetics*; Mitochondria/genetics; Central Nervous System Neoplasms/genetics; Microsatellite Repeats/genetics
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