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  1. Fulltext Molecular Breeding Strategy and Challenges Towards Improvement of Blast Disease Resistance in Rice Crop
    Ashkani S, Rafii MY, Shabanimofrad M, Miah G, Sahebi M, Azizi P, et al.
    Front Plant Sci, 2015;6:886.
    PMID: 26635817 DOI: 10.3389/fpls.2015.00886
    Rice is a staple and most important security food crop consumed by almost half of the world's population. More rice production is needed due to the rapid population growth in the world. Rice blast caused by the fungus, Magnaporthe oryzae is one of the most destructive diseases of this crop in different part of the world. Breakdown of blast resistance is the major cause of yield instability in several rice growing areas. There is a need to develop strategies providing long-lasting disease resistance against a broad spectrum of pathogens, giving protection for a long time over a broad geographic area, promising for sustainable rice production in the future. So far, molecular breeding approaches involving DNA markers, such as QTL mapping, marker-aided selection, gene pyramiding, allele mining and genetic transformation have been used to develop new resistant rice cultivars. Such techniques now are used as a low-cost, high-throughput alternative to conventional methods allowing rapid introgression of disease resistance genes into susceptible varieties as well as the incorporation of multiple genes into individual lines for more durable blast resistance. The paper briefly reviewed the progress of studies on this aspect to provide the interest information for rice disease resistance breeding. This review includes examples of how advanced molecular method have been used in breeding programs for improving blast resistance. New information and knowledge gained from previous research on the recent strategy and challenges towards improvement of blast disease such as pyramiding disease resistance gene for creating new rice varieties with high resistance against multiple diseases will undoubtedly provide new insights into the rice disease control.
    Matched MeSH terms: DNA Shuffling
  2. Fulltext Biomarkers for Bone Tumors: Discovery from Genomics and Proteomics Studies and Their Challenges
    Wan-Ibrahim WI, Singh VA, Hashim OH, Abdul-Rahman PS
    Mol. Med., 2016 Mar;21(1):861-872.
    PMID: 26581086 DOI: 10.2119/molmed.2015.00183
    Diagnosis of bone tumor currently relies on imaging and biopsy, and hence, the need to find less invasive ways for its accurate detection. More recently, numerous promising deoxyribonucleic acid (DNA) and protein biomarkers with significant prognostic, diagnostic and/or predictive abilities for various types of bone tumors have been identified from genomics and proteomics studies. This article reviewed the putative biomarkers for the more common types of bone tumors (that is, osteosarcoma, Ewing sarcoma, chondrosarcoma [malignant] and giant cell tumor [benign]) that were unveiled from the studies. The benefits and drawbacks of these biomarkers, as well as the technology platforms involved in the research, were also discussed. Challenges faced in the biomarker discovery studies and the problems in their translation from the bench to the clinical settings were also addressed.
    Matched MeSH terms: DNA
  3. Fulltext Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone
    Forde BM, Phan MD, Gawthorne JA, Ashcroft MM, Stanton-Cook M, Sarkar S, et al.
    mBio, 2015 Nov 17;6(6):e01602-15.
    PMID: 26578678 DOI: 10.1128/mBio.01602-15
    Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three (m6)A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for (m6)A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located.

    IMPORTANCE: DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone.

    Matched MeSH terms: DNA, Bacterial/metabolism*; DNA Methylation*
  4. Fulltext Genome Sequence of Complex HIV-1 Unique Recombinant Forms Sharing a Common Recombination Breakpoint Identified in Malaysia
    Cheong HT, Ng KT, Ong LY, Takebe Y, Chan KG, Koh C, et al.
    Genome Announc, 2015;3(6).
    PMID: 26543107 DOI: 10.1128/genomeA.01220-15
    Three strains of HIV-1 unique recombinant forms (URFs) descended from subtypes B, B', and CRF01_AE were identified among people who inject drugs in Kuala Lumpur, Malaysia. These three URFs shared a common recombination breakpoint in the reverse transcriptase region, indicating frequent linkage within the drug-injecting networks in Malaysia.
    Matched MeSH terms: RNA-Directed DNA Polymerase
  5. Human topoisomerase II alpha as a prognostic biomarker in cancer chemotherapy
    Ali Y, Abd Hamid S
    Tumour Biol., 2016 Jan;37(1):47-55.
    PMID: 26482620 DOI: 10.1007/s13277-015-4270-9
    Topoisomerases are nuclear enzymes that regulate topology of DNA by facilitating the temporary cleavage and ligation cycle of DNA. Among all forms of topoisomerases, TOP-IIA is extensively associated with cell proliferation and therefore is an important therapeutic target in diseases that involved cellular proliferation such as cancers. Nearly half of present-day antitumor regimens contain at least one prescription that act as a topoisomerase inhibitor. Generally, tumor cells show divergent expression of TOP-IIA compared to normal cells. The remarkable expression of TOP-IIA in various carcinomas provides a significant biomarker toward understanding the nature of malignancy. TOP-IIA expression and amplification studies help in diagnosing cancer and to observe the disease progression, overall survival (OS) of patients, and response to therapy. This review highlights the research output and analysis in exploring the standing of TOP-IIA in various carcinomas. As some reports show contradiction within the same field of interest, the outline of that may help to induce researchers for further investigation and clarification. To the best of our knowledge, this is the first overview briefly summarizing the prognostic feature of TOP-IIA in various types of cancer.
    Matched MeSH terms: DNA Topoisomerases, Type II/metabolism*; DNA-Binding Proteins/metabolism*
  6. Discovery of a new polyhydroxyalkanoate synthase from limestone soil through metagenomic approach
    Tai YT, Foong CP, Najimudin N, Sudesh K
    J Biosci Bioeng, 2016 Apr;121(4):355-64.
    PMID: 26467694 DOI: 10.1016/j.jbiosc.2015.08.008
    PHA synthase (PhaC) is the key enzyme in the production of biodegradable plastics known as polyhydroxyalkanoate (PHA). Nevertheless, most of these enzymes are isolated from cultivable bacteria using traditional isolation method. Most of the microorganisms found in nature could not be successfully cultivated due to the lack of knowledge on their growth conditions. In this study, a culture-independent approach was applied. The presence of phaC genes in limestone soil was screened using primers targeting the class I and II PHA synthases. Based on the partial gene sequences, a total of 19 gene clusters have been identified and 7 clones were selected for full length amplification through genome walking. The complete phaC gene sequence of one of the clones (SC8) was obtained and it revealed 81% nucleotide identity to the PHA synthase gene of Chromobacterium violaceum ATCC 12472. This gene obtained from uncultured bacterium was successfully cloned and expressed in a Cupriavidus necator PHB(-)4 PHA-negative mutant resulting in the accumulation of significant amount of PHA. The PHA synthase activity of this transformant was 64 ± 12 U/g proteins. This paper presents a pioneering study on the discovery of phaC in a limestone area using metagenomic approach. Through this study, a new functional phaC was discovered from uncultured bacterium. Phylogenetic classification for all the phaCs isolated from this study has revealed that limestone hill harbors a great diversity of PhaCs with activities that have not yet been investigated.
    Matched MeSH terms: DNA Primers
  7. Rare k-mer DNA: Identification of sequence motifs and prediction of CpG island and promoter
    Mohamed Hashim EK, Abdullah R
    J Theor Biol, 2015 Dec 21;387:88-100.
    PMID: 26427337 DOI: 10.1016/j.jtbi.2015.09.014
    Empirical analysis on k-mer DNA has been proven as an effective tool in finding unique patterns in DNA sequences which can lead to the discovery of potential sequence motifs. In an extensive study of empirical k-mer DNA on hundreds of organisms, the researchers found unique multi-modal k-mer spectra occur in the genomes of organisms from the tetrapod clade only which includes all mammals. The multi-modality is caused by the formation of the two lowest modes where k-mers under them are referred as the rare k-mers. The suppression of the two lowest modes (or the rare k-mers) can be attributed to the CG dinucleotide inclusions in them. Apart from that, the rare k-mers are selectively distributed in certain genomic features of CpG Island (CGI), promoter, 5' UTR, and exon. We correlated the rare k-mers with hundreds of annotated features using several bioinformatic tools, performed further intrinsic rare k-mer analyses within the correlated features, and modeled the elucidated rare k-mer clustering feature into a classifier to predict the correlated CGI and promoter features. Our correlation results show that rare k-mers are highly associated with several annotated features of CGI, promoter, 5' UTR, and open chromatin regions. Our intrinsic results show that rare k-mers have several unique topological, compositional, and clustering properties in CGI and promoter features. Finally, the performances of our RWC (rare-word clustering) method in predicting the CGI and promoter features are ranked among the top three, in eight of the CGI and promoter evaluations, among eight of the benchmarked datasets.
    Matched MeSH terms: DNA
  8. Fulltext A higher sensitivity and efficiency of common primer multiplex PCR assay in identification of meat origin using NADH dehydrogenase subunit 4 gene
    Hanapi UK, Desa MN, Ismail A, Mustafa S
    J Food Sci Technol, 2015 Jul;52(7):4166-75.
    PMID: 26139881 DOI: 10.1007/s13197-014-1459-7
    A Common Primer Multiplex PCR (CP-M-PCR) was developed to detect meat origin of four groups of animal (pig, ruminant, avian and rabbit). This method demonstrated higher sensitivity and efficiency than the conventional multiplex PCR. In this approach, a common forward primer was designed in the 5' end of a homologous region of mitochondrial NADH dehyrogenase subunit 4 (Nad 4) gene sequences of all the animal groups. Specific adapter reverse primers were designed by adding an adapter sequence at the 5' end. The same adapter sequence was used as the common adapter reverse primer. The primers generated specific fragments of 267, 370, 504, and 548 bp lengths for pig, ruminant, avian and rabbit meats, respectively. The use of adapter sequence at the 5' end of the common adapter reverse primers increased the efficiency of the amplification and the application of a common forward primer solved the complexity in multiplex PCR system. Bands of specific amplification can be detected in the PCR assays containing as low as 10(-6) μM of adapter reverse primer. This result indicated that the sensitivity was tremendously increased as compared to the conventional multiplex PCR (10(-3) μM). CP-M-PCR detection limit of the DNA samples was 0.1 ng for the four groups of meats. CP-M-PCR has greatly improved the sensitivity and efficiency of the PCR system for a more reliable and accurate outcome than conventional multiplex PCR system.
    Matched MeSH terms: DNA
  9. Fulltext The apparent interferon resistance of transmitted HIV-1 is possibly a consequence of enhanced replicative fitness
    Sugrue E, Wickenhagen A, Mollentze N, Aziz MA, Sreenu VB, Truxa S, et al.
    PLoS Pathog, 2022 Nov;18(11):e1010973.
    PMID: 36399512 DOI: 10.1371/journal.ppat.1010973
    HIV-1 transmission via sexual exposure is an inefficient process. When transmission does occur, newly infected individuals are colonized by the descendants of either a single virion or a very small number of establishing virions. These transmitted founder (TF) viruses are more interferon (IFN)-resistant than chronic control (CC) viruses present 6 months after transmission. To identify the specific molecular defences that make CC viruses more susceptible to the IFN-induced 'antiviral state', we established a single pair of fluorescent TF and CC viruses and used arrayed interferon-stimulated gene (ISG) expression screening to identify candidate antiviral effectors. However, we observed a relatively uniform ISG resistance of transmitted HIV-1, and this directed us to investigate possible underlying mechanisms. Simple simulations, where we varied a single parameter, illustrated that reduced growth rate could possibly underly apparent interferon sensitivity. To examine this possibility, we closely monitored in vitro propagation of a model TF/CC pair (closely matched in replicative fitness) over a targeted range of IFN concentrations. Fitting standard four-parameter logistic growth models, in which experimental variables were regressed against growth rate and carrying capacity, to our in vitro growth curves, further highlighted that small differences in replicative growth rates could recapitulate our in vitro observations. We reasoned that if growth rate underlies apparent interferon resistance, transmitted HIV-1 would be similarly resistant to any growth rate inhibitor. Accordingly, we show that two transmitted founder HIV-1 viruses are relatively resistant to antiretroviral drugs, while their matched chronic control viruses were more sensitive. We propose that, when present, the apparent IFN resistance of transmitted HIV-1 could possibly be explained by enhanced replicative fitness, as opposed to specific resistance to individual IFN-induced defences. However, further work is required to establish how generalisable this mechanism of relative IFN resistance might be.
    Matched MeSH terms: DNA Replication
  10. Fulltext Chloroplast Genome Analysis for Genetic Information and Authentication in Five Barleria Species
    Kaewdaungdee S, Sudmoon R, Tanee T, Lee SY, Chaveerach A
    Genes (Basel), 2022 Sep 22;13(10).
    PMID: 36292590 DOI: 10.3390/genes13101705
    In order to authenticate the genomic information of Barleriacristata L., B. lupulina Lindl., B. repens Nees, B. siamensis Craib, and B. strigosa Willd, cp genomes were investigated. They revealed a general structure with a total size of 151,997-152,324 bp. The genomes encoded a total of 131 genes, including 86 CDS, 37 tRNA, and 8 rRNA genes. Other details found were as follows: different numbers and types of SSRs; identical gene content, which is adjacent to the border regions, except for B. strigosa, that revealed a shorter ndhF gene sequence and lacked the ycf1 gene; slightly different genetic distance values, which can be used for species identification; three distinct gaps of nucleotide variations between the species located at the intergenic spacer regions of the LSC and CDS of the SSC; three effective molecular markers derived from divergent hotspot regions, including the ccsA-ndhD, ndhA-ndhH-rps15, and ycf1. The genetic relationships derived from the cp genome and the CDS phylogenetic trees of Barleria and the 13 genera in Acanthaceae and different families, Scrophulariaceae and Phrymaceae, showed similar results. The six Barleria species as monophyletic groups with inner and outer outgroups were found to have perfect discrimination. These results have helped to authenticate the five Barleria species and the six genera in Acanthaceae.
    Matched MeSH terms: DNA, Intergenic
  11. Fulltext SARS-CoV-2 detection by targeting four loci of viral genome using graphene oxide and gold nanoparticle DNA biosensor
    Babadi AA, Rahmati S, Fakhlaei R, Heidari R, Baradaran S, Akbariqomi M, et al.
    Sci Rep, 2022 Nov 12;12(1):19416.
    PMID: 36371566 DOI: 10.1038/s41598-022-23996-y
    The current COVID-19 pandemic outbreak poses a serious threat to public health, demonstrating the critical need for the development of effective and reproducible detection tests. Since the RT-qPCR primers are highly specific and can only be designed based on the known sequence, mutation sensitivity is its limitation. Moreover, the mutations in the severe acute respiratory syndrome β-coronavirus (SARS-CoV-2) genome led to new highly transmissible variants such as Delta and Omicron variants. In the case of mutation, RT-qPCR primers cannot recognize and attach to the target sequence. This research presents an accurate dual-platform DNA biosensor based on the colorimetric assay of gold nanoparticles and the surface-enhanced Raman scattering (SERS) technique. It simultaneously targets four different regions of the viral genome for detection of SARS-CoV-2 and its new variants prior to any sequencing. Hence, in the case of mutation in one of the target sequences, the other three probes could detect the SARS-CoV-2 genome. The method is based on visible biosensor color shift and a locally enhanced electromagnetic field and significantly amplified SERS signal due to the proximity of Sulfo-Cyanine 3 (Cy3) and AuNPs intensity peak at 1468 cm-1. The dual-platform DNA/GO/AuNP biosensor exhibits high sensitivity toward the viral genome with a LOD of 0.16 ng/µL. This is a safe point-of-care, naked-eye, equipment-free, and rapid (10 min) detection biosensor for diagnosing COVID-19 cases at home using a nasopharyngeal sample.
    Matched MeSH terms: DNA
  12. Fulltext International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic
    Lee VH, Adham M, Ben Kridis W, Bossi P, Chen MY, Chitapanarux I, et al.
    Lancet Oncol, 2022 Dec;23(12):e544-e551.
    PMID: 36455583 DOI: 10.1016/S1470-2045(22)00505-8
    The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.
    Matched MeSH terms: DNA
  13. A genetic Study of the Ghanaian Population Using 15 Autosomal STR Loci
    Kofi AE, Agyemang DA, Ghansah A, Awandare GA, Hakim HM, Khan HO, et al.
    Biochem Genet, 2023 Oct;61(5):1850-1866.
    PMID: 36869999 DOI: 10.1007/s10528-023-10347-3
    Autosomal short tandem repeat (STR) population data collected from a well characterized population are needed to correctly assigning the weight of DNA profiles in the courtroom and widely used for ancestral analyses. In this study, allele frequencies for the 15 autosomal short tandem repeat (STR) loci included in the AmpFlSTR® Identifiler® plus kit (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, FGA) were obtained by genotyping 332 unrelated individuals of Ghanaian origin. Statistical tests on STR genotype data showed no significant departure from Hardy-Weinberg equilibrium (HWE). The overall match probability, combined power of exclusion and combined power of discrimination for these loci were 1 in 3.85 × 1017, 0.99999893 and 0.99999998, respectively. Polymorphic information content (PIC) greater than 0.70 was observed for all loci except TH01 and D13S317. These statistical parameters confirm that this combination of loci is valuable for forensic identification and parentage analysis. Our results were also compared with those for 20 other human populations analyzed for the same set of markers. We observed that the Ghanaian population grouped with other African populations in two-dimensional principal coordinate (PCO) and a neighbor-joining (N-J) data mapping and placed closest to Nigerians. This observation reflects cultural similarities and geographical factors, coupled with the long history of migration and trading activities between Ghana and Nigeria. Our report provides what we believe to be the first published autosomal STR data for the general Ghanaian population using 15 loci genotyped using the AmpFlSTR® Identifiler® plus kit methodology. Our data show that the loci tested have sufficient power to be used reliably for DNA profiling in forensic casework and help to elucidate the genetic history of people living in the country.
    Matched MeSH terms: DNA Fingerprinting
  14. DNA methylation of ITGB2 contributes to allopurinol hypersensitivity
    Liu Y, Wang CW, Chen CB, Yu KH, Wu YJ, Choon SE, et al.
    Clin Immunol, 2023 Mar;248:109250.
    PMID: 36738816 DOI: 10.1016/j.clim.2023.109250
    BACKGROUNDS: HLA-B*58:01 allele was strongly associated with allopurinol induced severe cutaneous adverse drug reaction (SCAR). However, HLA-B genotype is not sufficient to predict the occurrence of allopurinol-induced SCAR.

    OBJECTIVE: To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing.

    STUDY DESIGN: The study was designed as a retrospective case-control clinical study in multicenter hospitals across Taiwan, Mainland China, Malaysia and Canada. 125 cases of allopurinol-induced SCAR patients and 139 cases of allopurinol tolerant controls were enrolled in this study during 2005 to 2021.

    RESULTS: The results of genome-wide DNA methylation assay of 62 patients revealed that ITGB2 showed strong discriminative ability of allopurinol-induced SCAR in both HLA-B*58:01 positive and negative patients with AUC value of 0.9364 (95% CI 0.8682-1.000). In validation study, significant hypermethylation of ITGB2 were further validated in allopurinol-induced SCAR patients compared to tolerant controls, especially in those without HLA-B*58:01(AUC value of 0.8814 (95% CI 0.7121-1.000)). Additionally, the methylation levels of 2 sites on ITGB2 were associated with SCAR phenotypes. Combination of HLA-B*58:01 genotyping and ITGB2 methylation status could improve the prediction accuracy of allopurinol-induced SCAR with the AUC value up to 0.9387 (95% CI 0.9089-0.9684), while the AUC value of HLA-B*58:01 genotyping alone was 0.8557 (95% CI 0.8030-0.9083).

    CONCLUSIONS: Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*58:01 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR.

    Matched MeSH terms: DNA Methylation
  15. Complete genome sequence analysis of the novel bacteriophage PA-1 infecting phytopathogenic Pantoea ananatis in Malaysia
    Singh PSS, Toh WK, Lim BH, Wong HL, Loh PC
    Arch Virol, 2025 Feb 17;170(3):60.
    PMID: 39961917 DOI: 10.1007/s00705-025-06239-z
    A novel bacteriophage, PA-1, was isolated using Pantoea ananatis, a bacterium that is responsible for rice leaf blight worldwide, as the host. PA-1 has a linear genome of 46,332 bp with a GC content of 50.55%. It contains 83 protein-encoding genes, and no tRNA-encoding genes were detected. The genome is densely organized, with an average CDS size of 516 bp, and 92.38% of the genome consists of protein-coding regions. Whole-genome sequencing and phylogenetic and morphological analysis showed that PA-1 is a novel phage that is phylogenetically distinct, suggesting that it may represent a new genus within the class Caudoviricetes.​.
    Matched MeSH terms: Sequence Analysis, DNA
  16. Small RNAs and Karma methylation in Elaeis guineensis mother palms are linked to high clonal mantling
    Ooi SE, Sarpan N, Taranenko E, Feshah I, Nuraziyan A, Roowi SH, et al.
    Plant Mol Biol, 2023 Mar;111(4-5):345-363.
    PMID: 36609897 DOI: 10.1007/s11103-022-01330-4
    The mantled phenotype is an abnormal somaclonal variant arising from the oil palm cloning process and severe phenotypes lead to oil yield losses. Hypomethylation of the Karma retrotransposon within the B-type MADS-box EgDEF1 gene has been associated with this phenotype. While abnormal Karma-EgDEF1 hypomethylation was detected in mantled clones, we examined the methylation state of Karma in ortets that gave rise to high mantling rates in their clones. Small RNAs (sRNAs) were proposed to play a role in Karma hypomethylation as part of the RNA-directed DNA methylation process, hence differential expression analysis of sRNAs between the ortet groups was conducted. While no sRNA was differentially expressed at the Karma-EgDEF1 region, three sRNA clusters were differentially regulated in high-mantling ortets. The first two down-regulated clusters were possibly derived from long non-coding RNAs while the third up-regulated cluster was derived from the intron of a DnaJ chaperone gene. Several predicted mRNA targets for the first two sRNA clusters conversely displayed increased expression in high-mantling relative to low-mantling ortets. These predicted mRNA targets may be associated with defense or pathogenesis response. In addition, several differentially methylated regions (DMRs) were identified in Karma and its surrounding regions, mainly comprising subtle CHH hypomethylation in high-mantling ortets. Four of the 12 DMRs were located in a region corresponding to hypomethylated areas at the 3'end of Karma previously reported in mantled clones. Further investigations on these sRNAs and DMRs may indicate the predisposition of certain ortets towards mantled somaclonal variation.
    Matched MeSH terms: DNA Methylation
  17. Shifting the pH profiles of Staphylococcus epidermidis lipase (SEL) and Staphylococcus hyicus lipase (SHL) through generating chimeric lipases by DNA shuffling strategy
    Hasan WANBW, Nezhad NG, Yaacob MA, Salleh AB, Rahman RNZRA, Leow TC
    World J Microbiol Biotechnol, 2024 Feb 22;40(4):106.
    PMID: 38386107 DOI: 10.1007/s11274-024-03927-x
    Enzymes are often required to function in a particular reaction condition by the industrial procedure. In order to identify critical residues affecting the optimum pH of Staphylococcal lipases, chimeric lipases from homologous lipases were generated via a DNA shuffling strategy. Chimeric 1 included mutations of G166S, K212E, T243A, H271Y. Chimeric 2 consisted of substitutions of K212E, T243A, H271Y. Chimeric 3 contained substitutions of K212E, R359L. From the screening results, the pH profiles for chimeric 1 and 2 lipases were shifted from pH 7 to 6. While the pH of chimeric 3 was shifted to 8. It seems the mutation of K212E in chimeric 1 and 2 decreased the pH to 6 by changing the electrostatic potential surface. Furthermore, chimeric 3 showed 10 ˚C improvement in the optimum temperature due to the rigidification of the catalytic loop through the hydrophobic interaction network. Moreover, the substrate specificity of chimeric 1 and 2 was increased towards the longer carbon length chains due to the mutation of T243A adjacent to the lid region through increasing the flexibility of the lid. Current study illustrated that directed evolution successfully modified lipase properties including optimum pH, temperature and substrate specificity through mutations, especially near catalytic and lid regions.
    Matched MeSH terms: DNA Shuffling
  18. Fulltext Cancer epigenetics: unraveling etiology and mechanisms to advance prevention
    Herceg Z, Ghantous A, Gheit T, Rahman Talukdar F, Matar C, Chung F, et al.
    J Natl Cancer Inst Monogr, 2026 Apr 01;2026(72):44-58.
    PMID: 42008732 DOI: 10.1093/jncimonographs/lgaf044
    The increased understanding of epigenetics has significantly advanced our understanding of cancer development, especially regarding environmental, occupational, and lifestyle exposures. Unlike genetic mutations, epigenetic changes may be reversible, making them critical mediators and promising targets for cancer prevention and control. This review synthesizes two decades of transformative research by the International Agency for Research on Cancer (IARC), which positioned the epigenome as a central focus in cancer epidemiology and mechanistic research among the 10 Key Characteristics (KCs) of carcinogens by the IARC Monographs program. From foundational in vitro and animal studies to large-scale population-based research, IARC researchers contributed to unraveling epigenetic mechanisms of carcinogenesis and identifying epigenetic biomarkers of exposures and cancer risk. We highlight progress in epigenetic biomarker development, mechanistic epigenomics, toxico-epigenomics, and the interplay between diet, microbiome, and epigenome. As IARC marks its 60th anniversary, this review underscores the growing role of epigenetics in guiding global cancer prevention efforts and public health strategies.
    Matched MeSH terms: DNA Methylation
  19. p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia
    Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N
    Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
    PMID: 29072413
    Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.
    Matched MeSH terms: DNA; DNA Primers
  20. Tri-parent Baby Technology and Preservation of Lineage: An Analysis from the Perspective of Maqasid al-Shari'ah Based Islamic Bioethics
    Ibrahim AH, Rahman NNA, Saifuddeen SM, Baharuddin M
    Sci Eng Ethics, 2019 02;25(1):129-142.
    PMID: 29071572 DOI: 10.1007/s11948-017-9980-5
    Tri-parent baby technology is an assisted reproductive treatment which aims to minimize or eliminate maternal inheritance of mutated mitochondrial DNA (mtDNA). The technology became popular following the move by the United Kingdom in granting license to a group of researchers from the Newcastle Fertility Centre, Newcastle University to conduct research on the symptoms of defective mtDNA. This technology differs from other assisted reproductive technology because it involves the use of gamete components retrieved from three different individuals. Indirectly, it affects the preservation of lineage which is important from an Islamic point of view. This paper aims to analyze and discuss the implications of the tri-parent technology on preservation of lineage from the perspective of Maqasid al-Shari'ah based the Islamic bioethics. The analysis shows that there are a few violations of the preservation of lineage, hence the tri-parent baby technology should not be permitted.
    Matched MeSH terms: DNA, Mitochondrial*
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