Displaying publications 241 - 260 of 8201 in total

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  1. Aslam S, Yee VC, Narayanan S, Duraisamy G, Standen GR
    Br J Haematol, 1997 Aug;98(2):346-52.
    PMID: 9266932
    Molecular analysis has been performed on a Malaysian patient with a severe bleeding disorder due to factor XIII(A) subunit deficiency. Total mRNA was isolated from the patient's leucocytes and four overlapping segments corresponding to the entire coding region of the A subunit cDNA were amplified by RT-PCR. The cDNA segments amplified efficiently and were of expected size. Direct sequencing of the complete reading frame revealed a single homozygous base change (nt 1327G-T) in exon 10 corresponding to a missense mutation, Val414Phe, in the catalytic core domain of the A subunit monomer. The mutation eliminates a BsaJ1 restriction site and family screening showed that both parents were heterozygous for the defect. The base substitution was absent in 55 normal individuals. Val414 is a highly conserved residue in the calcium-dependent transglutaminase enzyme family. Computer modelling based on 3D crystallographic data predicts that the bulky aromatic side chain of the substituted phenylalanine residue distorts protein folding and destabilizes the molecule. In addition, conformation changes in the adjacent catalytic and calcium binding regions of the A subunit are likely to impair the enzymatic activity of any protein synthesized.
    Matched MeSH terms: DNA/genetics; Exons/genetics; Factor XIII/genetics*; Factor XIII Deficiency/genetics*; Mutation/genetics*; RNA/genetics
  2. Takenaka A, Ueda S, Terao K, Takenaka O
    Mol Biol Evol, 1991 May;8(3):320-6.
    PMID: 2072861
    Alpha-globin genes in crab-eating macaques were found to be triplicated at high frequencies according to restriction-enzyme comparisons. The frequencies of triplicated alpha-globin genes in macaques originally from Malaysia and Indonesia were 0.432 and 0.275, respectively, while no triplication was found in individuals from either the Philippines or northern and central Thailand. Quadruplicated alpha-globin genes were also observed, at frequencies of 0.045 (Malaysia), 0.075 (Indonesia), and 0.021 (the Philippines). A single locus was detected in only one of 40 chromosomes from Indonesia (frequency 0.025).
    Matched MeSH terms: Animals, Wild/genetics; DNA/genetics; Globins/genetics*; Macaca fascicularis/genetics*; Malaria/genetics; Monkey Diseases/genetics
  3. Chow YP, Tan LP, Chai SJ, Abdul Aziz N, Choo SW, Lim PV, et al.
    Sci Rep, 2017 03 03;7:42980.
    PMID: 28256603 DOI: 10.1038/srep42980
    In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
    Matched MeSH terms: Carcinoma/genetics; DNA Repair/genetics; Nasopharyngeal Neoplasms/genetics; Biomarkers, Tumor/genetics; Signal Transduction/genetics; Exome/genetics*
  4. Rajagopalan K, Tay CH
    Arch Dermatol, 1977 Apr;113(4):481-5.
    PMID: 139851
    Hidrotic ectodermaldysplasia was found, to our knowledge, for the first time in a Chinese family in Malaysia, and it affected 15 members in five generations. The disease, which is transmitted as a non-sex-linked autosomal dominant trait, presumably originated from southern China. All 15 members had the typical nail, hair, and skin lesions, and we observed three different types of nail defects. Scalp alopeica was more extensive in the female members while keratoderma of the palms and soles was more notable in the male members. The nail and skin lesions also became severer with age. Except for the infectious eczematoid dermatitis present in the propositus, none had other skin or systemic disorders. All were relatively healthy and had normal life expectancies;
    Matched MeSH terms: Alopecia/genetics; Ectodermal Dysplasia/genetics*; Foot Dermatoses/genetics; Hand Dermatoses/genetics; Keratoderma, Palmoplantar/genetics; Nails, Malformed/genetics
  5. Nagaya D, Zahari Z, Saleem M, Yahaya BH, Tan SC, Yusoff NM
    J Clin Pharm Ther, 2018 Feb;43(1):80-86.
    PMID: 28656735 DOI: 10.1111/jcpt.12585
    WHAT IS KNOWN: Drug addiction is a novelty-seeking personality trait that is associated with the candidate genes OPRD1 (opioid delta receptors), OPRK1 (opioid kappa receptors) and PDYN (prodynorphin). However, associations between single nucleotide polymorphisms (SNPs) rs1042114 (80G>T) of the OPRD1 gene, rs702764 (843 A>G) of the OPRK1 gene, and rs910080 (3' UTR _743T>C), rs1997794 (5' UTR -381A>G) and rs1022563 (3' UTR) of the PDYN gene and novelty seeking remain controversial as reported results have not been reproducible.

    OBJECTIVE: The goal of this study was to determine the frequencies of SNPs rs1042114, rs702764, rs1997794, rs1022563 and rs910080 in the Malaysian population and to study their association with opioid dependence in Malaysian Malays.

    METHODS: A total of 459 Malay male with opioid dependence and 543 healthy male (controls) subjects were included in this study. SNPs were genotyped using the TaqMan SNP genotyping assay. Statistical analysis was performed using Golden Helix SVS software suite to identify the distribution of allele and genotype frequencies, and SNP-SNP interactions were also analysed in this study.

    RESULTS AND DISCUSSION: SNP rs1042114 in the OPRD1 gene is strongly associated with opiate addiction (P=.0001). In individuals homozygous for this risk allele, the likelihood of opiate addiction is increased by a factor 1.62 (95% confidence interval (CI) 1.412-1.875). Polymorphic alleles at SNP rs702764 of OPRK1 were not associated with opioid dependence. A significant association between opioid dependence and SNP rs910080 of PDYN (P=.0217) was detected, but there was no association for SNPs rs199774 and rs1022563. A significant interaction was also identified between homozygous wild-type genotype TT of rs702764 with the risk genotypes TG/GG of rs1042114 (odds ratio (OR)=2.111 (95% CI 1.227-3.631), P=.0069) and with the risk genotypes GA/AA of rs910080 (OR=1.415 (95% CI 1.04-1.912), P=.0239).

    WHAT IS NEW AND CONCLUSION: The results indicate that SNPs rs1042114 and rs910080 contribute to vulnerability to opioid dependence in the Malaysian Malay population. These results will help us to understand the effect of the SNPs and the SNP-SNP interaction on opioid dependence and may assist in efforts to screen vulnerable individuals and match them with individually tailored prevention and treatment strategies.

    Matched MeSH terms: Gene Frequency/genetics; Opioid-Related Disorders/genetics*; Receptors, Opioid, delta/genetics*; Receptors, Opioid, kappa/genetics*; Genetic Predisposition to Disease/genetics*; Polymorphism, Single Nucleotide/genetics*
  6. Wong YC, Teh HF, Mebus K, Ooi TEK, Kwong QB, Koo KL, et al.
    BMC Genomics, 2017 06 21;18(1):470.
    PMID: 28637447 DOI: 10.1186/s12864-017-3855-7
    BACKGROUND: The oil yield trait of oil palm is expected to involve multiple genes, environmental influences and interactions. Many of the underlying mechanisms that contribute to oil yield are still poorly understood. In this study, we used a microarray approach to study the gene expression profiles of mesocarp tissue at different developmental stages, comparing genetically related high- and low- oil yielding palms to identify genes that contributed to the higher oil-yielding palm and might contribute to the wider genetic improvement of oil palm breeding populations.

    RESULTS: A total of 3412 (2001 annotated) gene candidates were found to be significantly differentially expressed between high- and low-yielding palms at at least one of the different stages of mesocarp development evaluated. Gene Ontologies (GO) enrichment analysis identified 28 significantly enriched GO terms, including regulation of transcription, fatty acid biosynthesis and metabolic processes. These differentially expressed genes comprise several transcription factors, such as, bHLH, Dof zinc finger proteins and MADS box proteins. Several genes involved in glycolysis, TCA, and fatty acid biosynthesis pathways were also found up-regulated in high-yielding oil palm, among them; pyruvate dehydrogenase E1 component Subunit Beta (PDH), ATP-citrate lyase, β- ketoacyl-ACP synthases I (KAS I), β- ketoacyl-ACP synthases III (KAS III) and ketoacyl-ACP reductase (KAR). Sucrose metabolism-related genes such as Invertase, Sucrose Synthase 2 and Sucrose Phosphatase 2 were found to be down-regulated in high-yielding oil palms, compared to the lower yield palms.

    CONCLUSIONS: Our findings indicate that a higher carbon flux (channeled through down-regulation of the Sucrose Synthase 2 pathway) was being utilized by up-regulated genes involved in glycolysis, TCA and fatty acid biosynthesis leading to enhanced oil production in the high-yielding oil palm. These findings are an important stepping stone to understand the processes that lead to production of high-yielding oil palms and have implications for breeding to maximize oil production.

    Matched MeSH terms: Citric Acid Cycle/genetics; Fruit/genetics*; Glycolysis/genetics; Transcription Factors/genetics; Arecaceae/genetics*; Lipid Metabolism/genetics
  7. Hasan MJ, Shamsuzzaman SM
    Malays J Pathol, 2017 Dec;39(3):277-283.
    PMID: 29279590
    BACKGROUND: The adeB gene in Acinetobacter baumannii regulates the bacterial internal drug efflux pump that plays a significant role in drug resistance. The aim of our study was to determine the occurrence of adeB gene in multidrug resistant and New Delhi metallo-beta-lactamase-1 (NDM- 1) gene in imipenem resistant Acinetobacter baumannii isolated from wound swab samples in a tertiary care hospital of Bangladesh.

    METHODS: A total of 345 wound swab samples were tested for bacterial pathogens. Acinetobacter baumannii was identified by culture and biochemical tests. Antimicrobial susceptibility pattern was determined by the disc diffusion method according to CLSI standards. Extended spectrum beta-lactamases were screened using the double disc synergy technique. Gene encoding AdeB efflux pump and NDM-1 were detected by Polymerase Chain Reaction (PCR).

    RESULTS: A total 22 (6.37%) Acinetobacter baumannii were identified from 345 wound swab samples and 20 (91%) of them were multidrug resistant. High resistance rates to some antibiotics were seen namely, cefotaxime (95%), amoxyclavulanic acid (90%) and ceftriaxone (82%). All the identified Acinetobacter baumannii were sensitive to colistin and 82% to imipenem. Two (9%) ESBL producing Acinetobacter baumannii strains were detected. adeB gene was detected in 16 (80%) out of 20 multidrug resistant Acinetobacter baumannii. 4 (18%) of 22 Acinetobacter baumannii were imipenem resistant. NDM-1 gene was detected in 2 (50%) of the imipenem resistant strains of Acinetobacter baumannii.

    CONCLUSION: The results of this study provide insight into the role of adeB gene as a potential regulator of drug resistance in Acinetobacter baumanni in Bangladesh. NDM-1 gene also contributes in developing such resistance for Acinetobacter baumannii.

    Matched MeSH terms: Acinetobacter Infections/genetics*; Bacterial Proteins/genetics*; beta-Lactamases/genetics*; Wound Infection/genetics*; Drug Resistance, Multiple/genetics*; Membrane Transport Proteins/genetics*
  8. Ishar SM, Parameswaran K, Masduki NS, Rus Din RD
    PMID: 31709874 DOI: 10.1080/24701394.2019.1687693
    DNA variations are alterations found in DNA sequence, occurring in both nuclear DNA and mitochondrial DNA. Variations might differ in individual following population, respectively. The aim of this study was to find variations in target sequence of mtDNA (16000-16200) to be used as marker in Malay and Chinese population. A total of 30 buccal swab samples from 20 Malay and 10 Chinese subjects were collected and preserved on FTA card. The FTA card that contained DNA sample was punched to be included into polymerase chain reaction mixture. Amplification was carried out and the products were sequenced. Sequence variations were found in both Malay and Chinese populations. A total of nine variations (16129, 16108, 16162, 16172, 16148, 16127, 16173, 16099 and 16100) were found in Malay population while a total of seven variations (16129, 16104, 16111, 16109, 16164, 16170 and 16136) were found in Chinese population. Nucleotide position 16129 was found as variation in both Malay and Chinese populations. This study implies that np 16129 can be used as a marker for Malaysian population. For further investigation, the length of the target sequence may be increased to obtain more variations that can be used as markers. This will increase the discrimination power of Malaysian population.
    Matched MeSH terms: DNA, Mitochondrial/genetics*; Genetics, Population*; Genetic Variation/genetics*; Locus Control Region/genetics; Genome, Mitochondrial/genetics*
  9. Tan JSJ, Ong KC, Ong DBL, Wu YS, Razack A, Kuppusamy S, et al.
    Malays J Pathol, 2019 Dec;41(3):243-251.
    PMID: 31901908
    INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene.

    MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.

    RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent.

    CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

    Matched MeSH terms: Prostatic Hyperplasia/genetics; Prostatic Neoplasms/genetics*; Receptors, Androgen/genetics*; Gene Expression/genetics; Trinucleotide Repeats/genetics; Transcriptional Regulator ERG/genetics
  10. Feng S, Stiller J, Deng Y, Armstrong J, Fang Q, Reeve AH, et al.
    Nature, 2020 11;587(7833):252-257.
    PMID: 33177665 DOI: 10.1038/s41586-020-2873-9
    Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.
    Matched MeSH terms: Birds/genetics*; Chickens/genetics; Selection, Genetic/genetics; Genome/genetics*; Synteny/genetics; Finches/genetics
  11. Shen KN, Loh KH, Chen CH, Hsiao CD
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):4122-4123.
    PMID: 25585497
    In this study, the complete mitogenome sequence of the Blue-face angelfish, Pomacanthus xanthometapon (Perciformes: Pomacanthidae) has been sequenced by the next-generation sequencing method. The assembled mitogenome consisting of 16,533 bp includes 13 protein coding genes, 22 transfer RNAs, and two ribosomal RNAs genes. The overall base composition of Blue-face angelfish is 28.7% for A, 28.9% for C, 15.9% for G, 26.6% for T and show 84% identities to flame angelfish Centropyge loriculus. The complete mitogenome of the Blue-face angelfish provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for marine angelfish phylogeny.
    Matched MeSH terms: Base Composition/genetics; DNA, Mitochondrial/genetics; Perciformes/genetics*; RNA, Transfer/genetics; Genes, rRNA/genetics; Genome, Mitochondrial/genetics*
  12. Rizan N, Yew CY, Niknam MR, Krishnasamy J, Bhassu S, Hong GZ, et al.
    Sci Rep, 2018 01 17;8(1):896.
    PMID: 29343758 DOI: 10.1038/s41598-017-18825-6
    The exciting discovery of the semiconducting-like properties of deoxyribonucleic acid (DNA) and its potential applications in molecular genetics and diagnostics in recent times has resulted in a paradigm shift in biophysics research. Recent studies in our laboratory provide a platform towards detecting charge transfer mechanism and understanding the electronic properties of DNA based on the sequence-specific electronic response, which can be applied as an alternative to identify or detect DNA. In this study, we demonstrate a novel method for identification of DNA from different shrimp viruses and bacteria using electronic properties of DNA obtained from both negative and positive bias regions in current-voltage (I-V) profiles. Characteristic electronic properties were calculated and used for quantification and further understanding in the identification process. Aquaculture in shrimp industry is a fast-growing food sector throughout the world. However, shrimp culture in many Asian countries faced a huge economic loss due to disease outbreaks. Scientists have been using specific established methods for detecting shrimp infection, but those methods do have their significant drawbacks due to many inherent factors. As such, we believe that this simple, rapid, sensitive and cost-effective tool can be used for detection and identification of DNA from different shrimp viruses and bacteria.
    Matched MeSH terms: Bacteria/genetics; Bacterial Infections/genetics; DNA/genetics*; Virus Diseases/genetics; Viruses/genetics; Penaeidae/genetics*
  13. Lim KC, Then AY, Wee AKS, Sade A, Rumpet R, Loh KH
    Sci Rep, 2021 Jul 21;11(1):14874.
    PMID: 34290296 DOI: 10.1038/s41598-021-94257-7
    The demersal brown banded bamboo shark Chiloscyllium punctatum is a major component of sharks landed in Malaysia. However, little is known about their population structure and the effect of high fishing pressure on these weak swimming sharks. Both mitochondrial DNA control region (1072 bp) and NADH dehydrogenase subunit 2 (1044 bp) were used to elucidate the genetic structure and connectivity of C. punctatum among five major areas within the Sundaland region. Our findings revealed (i) strong genetic structure with little present day mixing between the major areas, (ii) high intra-population genetic diversity with unique haplotypes, (iii) significant correlation between genetic differentiation and geographical distance coupled with detectable presence of fine scale geographical barriers (i.e. the South China Sea), (iv) historical directional gene flow from the east coast of Peninsular Malaysia towards the west coast and Borneo, and (v) no detectable genetic differentiation along the coastline of east Peninsular Malaysia. Genetic patterns inferred from the mitochondrial DNA loci were consistent with the strong coastal shelf association in this species, the presence of contemporary barriers shaped by benthic features, and limited current-driven egg dispersal. Fine scale population structure of C. punctatum highlights the need to improve genetic understanding for fishery management and conservation of other small-sized sharks.
    Matched MeSH terms: DNA, Mitochondrial/genetics; Genetics, Population*; NADH Dehydrogenase/genetics; Sharks/genetics*; Genetic Variation/genetics*
  14. Ram SP, Noor AR, Ariffin WA, Ariffin NA
    Singapore Med J, 1994 Apr;35(2):205-7.
    PMID: 7939823
    A 37-week gestation male boy was born to a gravida seven para six mother by spontaneous vertex delivery at home. The baby cried at birth. On day 3 of life, he was admitted for respiratory distress. Physical examination revealed ectrodactyly, thin dry skin, anomalous tear duct with cardiomegaly. X-ray revealed absent radii, cardiomegaly and hemivertebra at L1. Echocardiogram revealed perimembranous type of ventricular septal defect. A diagnosis of Ectodermal Dysplasia Ectrodactyly Clefting Syndrome with ventricular septal defect was made. He was managed conservatively in the nursery. However, he expired on day 27 of life following short spell of fever apnoeic episode due to neonatal sepsis.
    Matched MeSH terms: Abnormalities, Multiple/genetics*; Cleft Lip/genetics*; Cleft Palate/genetics*; Ectodermal Dysplasia/genetics*; Ectromelia/genetics*; Heart Septal Defects, Ventricular/genetics*
  15. Hamilton MG, Mekkawy W, Benzie JAH
    Genet. Sel. Evol., 2019 Apr 29;51(1):17.
    PMID: 31035934 DOI: 10.1186/s12711-019-0454-x
    Catla catla (Hamilton) fertilised spawn was collected from the Halda, Jamuna and Padma rivers in Bangladesh from which approximately 900 individuals were retained as 'candidate founders' of a breeding population. These fish were fin-clipped and genotyped using the DArTseq platform to obtain, 3048 single nucleotide polymorphisms (SNPs) and 4726 silicoDArT markers. Using SNP data, individuals that shared no putative parents were identified using the program COLONY, i.e. 140, 47 and 23 from the Halda, Jamuna and Padma rivers, respectively. Allele frequencies from these individuals were considered as representative of those of the river populations, and genomic relationship matrices were generated. Then, half-sibling and full-sibling relationships between individuals were assigned manually based on the genomic relationship matrices. Many putative half-sibling and full-sibling relationships were found between individuals from the Halda and Jamuna rivers, which suggests that catla sampled from rivers as spawn are not necessarily representative of river populations. This has implications for the interpretation of past population genetics studies, the sampling strategies to be adopted in future studies and the management of broodstock sourced as river spawn in commercial hatcheries. Using data from individuals that shared no putative parents, overall multi-locus pairwise estimates of Wright's fixation index (FST) were low (≤ 0.013) and the optimum number of clusters using unsupervised K-means clustering was equal to 1, which indicates little genetic divergence among the SNPs included in our study within and among river populations.
    Matched MeSH terms: Carps/genetics*; Cyprinidae/genetics; Gene Frequency/genetics; Genetics, Population/methods*; Polymorphism, Single Nucleotide/genetics
  16. Hall HN, Bengani H, Hufnagel RB, Damante G, Ansari M, Marsh JA, et al.
    PLoS One, 2022;17(11):e0268149.
    PMID: 36413568 DOI: 10.1371/journal.pone.0268149
    Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism.
    Matched MeSH terms: Eye Proteins/genetics; Transcription Factors/genetics; RNA-Binding Proteins/genetics; Homeodomain Proteins/genetics; Intracellular Signaling Peptides and Proteins/genetics; PAX6 Transcription Factor/genetics
  17. Riyadi FA, Tahir AA, Yusof N, Sabri NSA, Noor MJMM, Akhir FNMD, et al.
    Sci Rep, 2020 05 08;10(1):7813.
    PMID: 32385385 DOI: 10.1038/s41598-020-64817-4
    The conversion of lignocellulosic biomass into bioethanol or biochemical products requires a crucial pretreatment process to breakdown the recalcitrant lignin structure. This research focuses on the isolation and characterization of a lignin-degrading bacterial strain from a decaying oil palm empty fruit bunch (OPEFB). The isolated strain, identified as Streptomyces sp. S6, grew in a minimal medium with Kraft lignin (KL) as the sole carbon source. Several known ligninolytic enzyme assays were performed, and lignin peroxidase (LiP), laccase (Lac), dye-decolorizing peroxidase (DyP) and aryl-alcohol oxidase (AAO) activities were detected. A 55.3% reduction in the molecular weight (Mw) of KL was observed after 7 days of incubation with Streptomyces sp. S6 based on gel-permeation chromatography (GPC). Gas chromatography-mass spectrometry (GC-MS) also successfully highlighted the production of lignin-derived aromatic compounds, such as 3-methyl-butanoic acid, guaiacol derivatives, and 4,6-dimethyl-dodecane, after treatment of KL with strain S6. Finally, draft genome analysis of Streptomyces sp. S6 also revealed the presence of strong lignin degradation machinery and identified various candidate genes responsible for lignin depolymerization, as well as for the mineralization of the lower molecular weight compounds, confirming the lignin degradation capability of the bacterial strain.
    Matched MeSH terms: Alcohol Oxidoreductases/genetics; Lignin/genetics; Peroxidase/genetics; Peroxidases/genetics; Streptomyces/genetics; Laccase/genetics
  18. Liew SC, Gupta ED
    Eur J Med Genet, 2015 Jan;58(1):1-10.
    PMID: 25449138 DOI: 10.1016/j.ejmg.2014.10.004
    The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with various diseases (vascular, cancers, neurology, diabetes, psoriasis, etc) with the epidemiology of the polymorphism of the C677T that varies dependent on the geography and ethnicity. The 5,10-Methylenetetrahydrofolate reductase (MTHFR) locus is mapped on chromosome 1 at the end of the short arm (1p36.6). This enzyme is important for the folate metabolism which is an integral process for cell metabolism in the DNA, RNA and protein methylation. The mutation of the MTHFR gene which causes the C677T polymorphism is located at exon 4 which results in the conversion of valine to alanine at codon 222, a common polymorphism that reduces the activity of this enzyme. The homozygous mutated subjects have higher homocysteine levels while the heterozygous mutated subjects have mildly raised homocysteine levels compared with the normal, non-mutated controls. Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education. This literature review therefore focuses on the recent evidence-based reports on the associations of the MTHFR C677T polymorphism and the various diseases globally.
    Matched MeSH terms: Mental Disorders/genetics; Diabetes Mellitus/genetics; Infertility/genetics; Neoplasms/genetics; Nervous System Diseases/genetics; Psoriasis/genetics; Vascular Diseases/genetics; Methylenetetrahydrofolate Reductase (NADPH2)/genetics*
  19. Faber BW, Abdul Kadir K, Rodriguez-Garcia R, Remarque EJ, Saul FA, Vulliez-Le Normand B, et al.
    PLoS One, 2015;10(4):e0124400.
    PMID: 25881166 DOI: 10.1371/journal.pone.0124400
    Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.
    Matched MeSH terms: Antigens, Protozoan/genetics*; Haplotypes/genetics*; Malaria/genetics*; Membrane Proteins/genetics*; Mutation/genetics*; Polymorphism, Genetic/genetics*; Selection, Genetic/genetics*; Protozoan Proteins/genetics*
  20. Liew PS, Tan TH, Wong YC, Sim EUH, Lee CW, Narayanan K
    ACS Synth Biol, 2020 04 17;9(4):804-813.
    PMID: 32196315 DOI: 10.1021/acssynbio.9b00478
    TelN and tos are a unique DNA linearization unit isolated from bacteriophage N15. While being transferable, the TelN cleaving-rejoining activities remained stable to function on tos in both bacterial and mammalian environments. However, TelN contribution in linear plasmid replication in mammalian cells remains unknown. Herein, we investigated the association of TelN in linear tos-containing DNA (tos-DNA) replication in mammalian cells. Additionally, the mammalian origin of replication (ori) that is well-known to initiate the replication event of plasmid vectors was also studied. In doing so, we identified that both TelN and mammalian initiation sites were essential for the replication of linear tos-DNA, determined by using methylation sensitive DpnI/MboI digestion and polymerase chain reaction (PCR) amplification approaches. Furthermore, we engineered the linear tos-DNA to be able to retain in mammalian cells using S/MAR technology. The resulting S/MAR containing tos-DNA was robust for at least 15 days, with (1) continuous tos-DNA replication, (2) correct splicing of gene transcripts, and (3) stable exogenous gene expression that was statistically comparable to the endogenous gene expression level. Understanding the activities of TelN and tos in mammalian cells can potentially provide insights for adapting this simple DNA linearization unit in developing novel genetic engineering tools, especially to the eukaryotic telomere/telomerase study.
    Matched MeSH terms: Bacteriophages/genetics; DNA Replication/genetics*; DNA, Viral/genetics; Enzyme Precursors/genetics*; Plasmids/genetics; Viral Proteins/genetics*; Telomerase/genetics*; Matrix Attachment Regions/genetics
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