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  1. Genotyping of Malaysian G6PD-deficient neonates by reverse dot blot flow-through hybridisation
    Alina MF, Azma RZ, Norunaluwar J, Azlin I, Darnina AJ, Cheah FC, et al.
    J Hum Genet, 2020 Mar;65(3):263-270.
    PMID: 31863082 DOI: 10.1038/s10038-019-0700-7
    G6PD deficiency is the commonest enzyme deficiency found in humans. Current diagnostic methods lack sensitivity to detect all cases of G6PD deficiency. We evaluated the reverse dot blot flow-through hybridisation assay designed to detect simultaneously multiple known G6PD mutations in a group of Malaysian neonates. Archival DNA samples from 141 G6PD-deficient neonates were subjected to reverse dot blot flow-through hybridisation assay using the GenoArray Diagnostic Kit (Hybribio Limited, Hong Kong) and DNA sequencing. The method involved PCR amplification of 5 G6PD exons using biotinylated primers, hybridisation of amplicons to a membrane containing oligoprobes designed for G6PD mutations known to occur in the Malaysian population and colour detection by enzyme immunoassay. The assay detected 13 of the 14 G6PD mutations and genotyped 133 (94.3%) out of 141 (102 males, 39 females) cases. Among the 39 female G6PD-deficient neonates, there were 7 homozygous and 6 compound heterozygous cases. The commonest alleles were G6PD Viangchan 871G > A (21%) and G6PD Mahidol 487G > A(20%) followed by G6PD Mediterranean 563C > T, (14%), G6PD Vanua Lava 383T > C (12%), G6PD Canton 1376G > T (10%), G6PD Orissa 131C > G (6.3%) G6PD Coimbra 592C > T (5.6%) plus 6 other mutations. DNA sequencing of remaining cases revealed 6 cases of intron 11 nt 93C > T not previously reported in Malaysia and two novel mutations, one case each of nt 1361G > T and nt 1030G > A. We found the reverse dot blot assay easy to perform, rapid, accurate and reproducible, potentially becoming an improved diagnostic test for G6PD deficiency.
    Matched MeSH terms: Introns/genetics
  2. Spectrum of germ-line RB1 gene mutations in Malaysian patients with retinoblastoma
    Mohd Khalid MK, Yakob Y, Md Yasin R, Wee Teik K, Siew CG, Rahmat J, et al.
    Mol Vis, 2015;21:1185-90.
    PMID: 26539030
    The availability of molecular genetic testing for retinoblastoma (RB) in Malaysia has enabled patients with a heritable predisposition to the disease to be identified, which thus improves the clinical management of these patients and their families. In this paper, we presented our strategy for performing molecular genetic testing of the RB1 gene and the findings from our first 2 years of starting this service.
    Matched MeSH terms: Introns
  3. Fulltext Hemolytic anemia and distal renal tubular acidosis in two Indian patients homozygous for SLC4A1/AE1 mutation A858D
    Shmukler BE, Kedar PS, Warang P, Desai M, Madkaikar M, Ghosh K, et al.
    Am J Hematol, 2010 Oct;85(10):824-8.
    PMID: 20799361 DOI: 10.1002/ajh.21836
    Familial distal renal tubular acidosis (dRTA) can be caused by mutations in the Cl2/HCO32 exchanger of the renal Type A intercalated cell, kidney AE1/SLC4A1. dRTA-associated AE1 mutations have been reported in families from North America, Europe, Thailand, Malaysia, Papua-New Guinea, Taiwan, and the Philippines, but not India. The dRTA mutation AE1 A858D has been detected only in the context of compound heterozygosity. We report here two unrelated Indian patients with combined hemolytic anemia and dRTA who share homozygous A858D mutations of the AE1/SLC4A1 gene. The mutation creates a novel restriction site that is validated for diagnostic screening.
    Matched MeSH terms: Introns/genetics
  4. Fulltext MLH1 and MSH2 gene mutations and polymorphisms in six Malay families with hereditary nonpolyposis colorectal cancer
    Wan Khairunnisa Wan Juhari, Khairul Bariah Ahmad Amin Noordin, Wan Faiziah Wan Abdul Rahman, Andee Dzulkarnaen Zakaria, Ahmad Shanwani Mohd Sidek, Muhammad Radzi Abu Hassan, et al.
    International Medical Journal Malaysia, 2018;17(1):71-78.
    MyJurnal
    Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.
    Matched MeSH terms: Introns
  5. The 27-bp VNTR polymorphism in intron 4 of the human eNOS gene in healthy Singaporean Chinese, Indians, and Malays
    Gan YY, Chen CF
    Biochem Genet, 2012 Feb;50(1-2):52-62.
    PMID: 21927815 DOI: 10.1007/s10528-011-9458-0
    Human endothelial nitric oxide synthase (eNOS) is one isoform of the nitric oxide synthases that are responsible for nitric oxide synthesis from L-arginine. The gene encoding eNOS contains a 27-bp VNTR polymorphism in intron 4. We report here for the first time the presence of a novel allele 3, which was absent in all other populations studied to date, in 1.7% each of Singaporean Indians and Malays. We also detected the presence of a novel genotype 3/5 in 3.4% each of Singaporean Indians and Malays. Allele 6, which was absent in Han Chinese from northern China and Taiwan and was also absent in Indians from the Indian subcontinent, was found in 2.1% of Singaporean Chinese and in 0.3% of Singaporean Indians.
    Matched MeSH terms: Introns
  6. EGFR Intron 1 polymorphism in Asian Populations and its correlation with EGFR gene expression and amplification in breast tumor tissues
    Zhou Q, Cheung YB, Jada SR, Lim WT, Kuo WL, Gray JW, et al.
    Cancer Biol Ther, 2006 Nov;5(11):1445-9.
    PMID: 17102595
    AIM: The purpose of this study was to test the hypothesis if longer CA dinucleotide repeats are more common in the Asian population and also to gain insights into the interplay between the CA dinucleotide repeats and the frequencies of EGFR gene expression and amplifications as this might have therapeutic implications with regards to treatment with tyrosine kinase inhibitors.

    MATERIALS AND METHODS: The EGFR intron 1 polymorphism was analysed in three distinct healthy Asian subjects, namely, Chinese (N = 96), Malays (N = 98) and Indians (N = 100). Comparative genomic hybridisation was performed to investigate for changes in DNA copy number in relation to the polymorphic CA dinucleotide repeats in breast tumor tissues (N = 22).

    RESULTS: The frequency of short alleles with 14 and 15 CA repeats were most common in the Asian populations and significantly higher than those reported for Caucasians. The frequency of 20 CA repeats was 5%, almost 13-fold lower than previous reports. EGFR amplifications were detected in 23% and 11% of breast tumor tissues harboring short and long CA repeats, respectively.

    CONCLUSION: Our results show that the frequency of alleles encoding for short CA dinucleotide repeats is common in Asian populations. EGFR expression and amplification levels were also higher in Asian breast tumor tissues with short CA dinucleotide repeats. These findings suggest that the EGFR intron 1 polymorphism may influence response to treatment with tyrosine kinase inhibitors in breast cancer patients and further studies are warranted.

    Matched MeSH terms: Introns*
  7. Strategies for the Construction of Cassava Brown Streak Disease Viral Infectious Clones
    Duff-Farrier CRA, Mbanzibwa DR, Nanyiti S, Bunawan H, Pablo-Rodriguez JL, Tomlinson KR, et al.
    Mol Biotechnol, 2019 Feb;61(2):93-101.
    PMID: 30484144 DOI: 10.1007/s12033-018-0139-7
    Cassava brown streak disease (CBSD) has major impacts on yield and quality of the tuberous roots of cassava in Eastern and Central Arica. At least two Potyviridae species cause the disease: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Cloned viral genome sequences known as infectious clones (ICs) have been important in the study of other viruses, both as a means of standardising infectious material and characterising viral gene function. IC construction is often technically challenging for Potyviridae due to sequence instability in E. coli. Here, we evaluate three methods for the construction of infectious clones for CBSD. Whilst a simple IC for in vitro transcription was made for UCBSV isolate 'Kikombe', such an approach failed to deliver full-length clones for CBSV isolates 'Nampula' or 'Tanza', necessitating more complex approaches for their construction. The ICs successfully generated symptomatic infection in the model host N. benthamiana and in the natural host cassava. This shows that whilst generating ICs for CBSV is still a technical challenge, a structured approach, evaluating both in vitro and in planta transcription systems should successfully deliver ICs, allowing further study into the symptomology and virulence factors in this important disease complex.
    Matched MeSH terms: Introns/genetics
  8. Fulltext Genome-Wide Computational Identification of Biologically Significant Cis-Regulatory Elements and Associated Transcription Factors from Rice
    Ho CL, Geisler M
    Plants (Basel), 2019 Oct 23;8(11).
    PMID: 31652796 DOI: 10.3390/plants8110441
    The interactions between transcription factors (TFs) and cis-acting regulatory elements (CREs) provide crucial information on the regulation of gene expression. The determination of TF-binding sites and CREs experimentally is costly and time intensive. An in silico identification and annotation of TFs, and the prediction of CREs from rice are made possible by the availability of whole genome sequence and transcriptome data. In this study, we tested the applicability of two algorithms developed for other model systems for the identification of biologically significant CREs of co-expressed genes from rice. CREs were identified from the DNA sequences located upstream from the transcription start sites, untranslated regions (UTRs), and introns, and downstream from the translational stop codons of co-expressed genes. The biologically significance of each CRE was determined by correlating their absence and presence in each gene with that gene's expression profile using a meta-database constructed from 50 rice microarray data sets. The reliability of these methods in the predictions of CREs and their corresponding TFs was supported by previous wet lab experimental data and a literature review. New CREs corresponding to abiotic stresses, biotic stresses, specific tissues, and developmental stages were identified from rice, revealing new pieces of information for future experimental testing. The effectiveness of some-but not all-CREs was found to be affected by copy number, position, and orientation. The corresponding TFs that were most likely correlated with each CRE were also identified. These findings not only contribute to the prioritization of candidates for further analysis, the information also contributes to the understanding of the gene regulatory network.
    Matched MeSH terms: Introns
  9. The clinical severity of beta-thalassemia mutations in West Malaysia
    George E
    Southeast Asian J. Trop. Med. Public Health, 1995;26 Suppl 1:225-8.
    PMID: 8629111
    Beta-thalassemia in West Malaysia is caused by 14 molecular defects with differing clinical severity. In Chinese patients from West Malaysia, the main beta-thalassemia mutations seen were (a) a 4 base pair-TCTT deletion in codon 41-42 [frameshift mutation (FSC 41-42)]; (b) a C to T substitution at the second intervening sequence (IVS2-654); (c) an A to G substitution in the TATA box [-28 (A to G)], and (d) an A to T substitution in codon 17[17 A to T]. In the Malays, the main mutations seen were (a) a G to C in nucleotide 5 at the intervening sequence I [IVS1-5 (G to C)]; (b) G to T substitution in nucleotide I at the intervening sequence I [IVS1-1 (G to T)]; (c) a A to T substitution in codon 17 (17 A to T); (d) removal of C from codon 35 [codon 35 (-C)], and (e) a 4 base pairs-TCTT deletion in codon 41-42 [frameshift mutation (FSC 41-42)]. A scoring system (Tha1 CS) has been formulated to predict clinical severity. It is the type of beta-thalassemia mutation present that decides on the clinical phenotype. The most severe beta-thalassemia mutation is assigned a score of 4. A score of 8 indicates severe thalassemia.
    Matched MeSH terms: Introns
  10. Fulltext Escaping introns in COI through cDNA barcoding of mushrooms: Pleurotus as a test case
    Avin FA, Subha B, Tan YS, Braukmann TWA, Vikineswary S, Hebert PDN
    Ecol Evol, 2017 09;7(17):6972-6980.
    PMID: 28904776 DOI: 10.1002/ece3.3049
    DNA barcoding involves the use of one or more short, standardized DNA fragments for the rapid identification of species. A 648-bp segment near the 5' terminus of the mitochondrial cytochrome c oxidase subunit I (COI) gene has been adopted as the universal DNA barcode for members of the animal kingdom, but its utility in mushrooms is complicated by the frequent occurrence of large introns. As a consequence, ITS has been adopted as the standard DNA barcode marker for mushrooms despite several shortcomings. This study employed newly designed primers coupled with cDNA analysis to examine COI sequence diversity in six species of Pleurotus and compared these results with those for ITS. The ability of the COI gene to discriminate six species of Pleurotus, the commonly cultivated oyster mushroom, was examined by analysis of cDNA. The amplification success, sequence variation within and among species, and the ability to design effective primers was tested. We compared ITS sequences to their COI cDNA counterparts for all isolates. ITS discriminated between all six species, but some sequence results were uninterpretable, because of length variation among ITS copies. By comparison, a complete COI sequences were recovered from all but three individuals of Pleurotus giganteus where only the 5' region was obtained. The COI sequences permitted the resolution of all species when partial data was excluded for P. giganteus. Our results suggest that COI can be a useful barcode marker for mushrooms when cDNA analysis is adopted, permitting identifications in cases where ITS cannot be recovered or where it offers higher resolution when fresh tissue is. The suitability of this approach remains to be confirmed for other mushrooms.
    Matched MeSH terms: Introns
  11. Rampant polyphyly in the Arracacia clade (Apiaceae) and an assessment of the phylogenetic utility of 20 noncoding plastid loci
    Danderson CA, Downie SR, Hermann M
    Mol Phylogenet Evol, 2018 01;118:286-305.
    PMID: 29017853 DOI: 10.1016/j.ympev.2017.10.006
    The Arracacia clade (Apiaceae, Apioideae) is a heterogeneous assemblage of 12 genera, comprising 111 known species distributed in high montane temperate and sub-alpine habitats of meso- and South America. Previous studies have indicated that the genera Arracacia, Coulterophytum, and Prionosciadium are polyphyletic, but for the most part relationships among the members of the clade are largely unknown. Initially, cladistic analyses of nrDNA ITS sequences were carried out on 212 accessions (122 taxa), representing 92 species of the Arracacia clade and outgroups from the closely-related páramo genera Cotopaxia, Niphogeton, and Perissocoeleum and members of the Perennial Endemic North American clade and its allies. Using the ITS results to inform sampling of a small subset of taxa, a pilot study examining the phylogenetic utility of 20 noncoding chloroplast loci was subsequently performed to identify those regions most useful at resolving relationships. A cost-benefit analysis determined that five loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, psbD-trnT, ndhA intron) would maximize resolution and branch support in the clade. Cladistic analyses of four of these loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, ndhA intron) and the ITS region, separately and combined, revealed that Arracacia, Coaxana, Coulterophytum, Prionosciadium, and Rhodosciadium are each polyphyletic and that Donnellsmithia and Myrrhidendron are each monophyletic. Although most relationships in the Arracacia clade and among the closely-related genera Cotopaxia, Niphogeton, and Perissocoeleum are poorly resolved and supported, ten groups are recognized for future revisionary studies. Polyploidy and rapid species radiation have likely confounded generic circumscriptions and interpretation of relationships.
    Matched MeSH terms: Introns
  12. Fulltext Whole genome sequencing of Rhodotorula mucilaginosa isolated from the chewing stick (Distemonanthus benthamianus): insights into Rhodotorula phylogeny, mitogenome dynamics and carotenoid biosynthesis
    Gan HM, Thomas BN, Cavanaugh NT, Morales GH, Mayers AN, Savka MA, et al.
    PeerJ, 2017;5:e4030.
    PMID: 29158974 DOI: 10.7717/peerj.4030
    In industry, the yeast Rhodotorula mucilaginosa is commonly used for the production of carotenoids. The production of carotenoids is important because they are used as natural colorants in food and some carotenoids are precursors of retinol (vitamin A). However, the identification and molecular characterization of the carotenoid pathway/s in species belonging to the genus Rhodotorula is scarce due to the lack of genomic information thus potentially impeding effective metabolic engineering of these yeast strains for improved carotenoid production. In this study, we report the isolation, identification, characterization and the whole nuclear genome and mitogenome sequence of the endophyte R. mucilaginosa RIT389 isolated from Distemonanthus benthamianus, a plant known for its anti-fungal and antibacterial properties and commonly used as chewing sticks. The assembled genome of R. mucilaginosa RIT389 is 19 Mbp in length with an estimated genomic heterozygosity of 9.29%. Whole genome phylogeny supports the species designation of strain RIT389 within the genus in addition to supporting the monophyly of the currently sequenced Rhodotorula species. Further, we report for the first time, the recovery of the complete mitochondrial genome of R. mucilaginosa using the genome skimming approach. The assembled mitogenome is at least 7,000 bases larger than that of Rhodotorula taiwanensis which is largely attributed to the presence of large intronic regions containing open reading frames coding for homing endonuclease from the LAGLIDADG and GIY-YIG families. Furthermore, genomic regions containing the key genes for carotenoid production were identified in R. mucilaginosa RIT389, revealing differences in gene synteny that may play a role in the regulation of the biotechnologically important carotenoid synthesis pathways in yeasts.
    Matched MeSH terms: Introns
  13. Fulltext Purification of an alpha amylase from Aspergillus flavus NSH9 and molecular characterization of its nucleotide gene sequence
    Karim KMR, Husaini A, Sing NN, Sinang FM, Roslan HA, Hussain H
    3 Biotech, 2018 Apr;8(4):204.
    PMID: 29607285 DOI: 10.1007/s13205-018-1225-z
    In this study, an alpha-amylase enzyme from a locally isolated Aspergillus flavus NSH9 was purified and characterized. The extracellular α-amylase was purified by ammonium sulfate precipitation and anion-exchange chromatography at a final yield of 2.55-fold and recovery of 11.73%. The molecular mass of the purified α-amylase was estimated to be 54 kDa using SDS-PAGE and the enzyme exhibited optimal catalytic activity at pH 5.0 and temperature of 50 °C. The enzyme was also thermally stable at 50 °C, with 87% residual activity after 60 min. As a metalloenzymes containing calcium, the purified α-amylase showed significantly increased enzyme activity in the presence of Ca2+ ions. Further gene isolation and characterization shows that the α-amylase gene of A. flavus NSH9 contained eight introns and an open reading frame that encodes for 499 amino acids with the first 21 amino acids presumed to be a signal peptide. Analysis of the deduced peptide sequence showed the presence of three conserved catalytic residues of α-amylase, two Ca2+-binding sites, seven conserved peptide sequences, and several other properties that indicates the protein belongs to glycosyl hydrolase family 13 capable of acting on α-1,4-bonds only. Based on sequence similarity, the deduced peptide sequence of A. flavus NSH9 α-amylase was also found to carry two potential surface/secondary-binding site (SBS) residues (Trp 237 and Tyr 409) that might be playing crucial roles in both the enzyme activity and also the binding of starch granules.
    Matched MeSH terms: Introns
  14. BRCA1 c.2845insA is a recurring mutation with a founder effect in Singapore Malay women with early onset breast/ovarian cancer
    Sng JH, Ali AB, Lee SC, Zahar D, Wong JE, Blake V, et al.
    J Med Genet, 2003 Oct;40(10):e117.
    PMID: 14569140
    Matched MeSH terms: Introns
  15. A case of beta-thalassemia with a C----T substitution at position 654 of the second intervening sequence of the beta-globin gene
    Jo T, Momita S, Sadamori N, Tomonaga M, Fucharoem S, Fukumaki Y, et al.
    Intern. Med., 1992 Feb;31(2):269-72.
    PMID: 1600278
    A 26-year-old Chinese-Malaysian female patient with beta-thalassemia is presented. The main hematological values found in this patient were as follows: 1) normocytic hypochromic anemia (RBC 444 x 10(4)/microliters, Hb 11.8 g/dl) with marked anisopoikilocytosis, 2) erythroid hyperplasia, and 3) increased HbF (HbA 41.4%, HbA2 2.9%, HbF 48.9%). DNA obtained from peripheral leukocytes was analyzed using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA with allele-specific oligonucleotide probes. A C----T substitution at position 654 of the second intervening sequence (IVS-2) was detected in her beta-globin clone.
    Matched MeSH terms: Introns
  16. Screening of Transforming Growth Factor Beta 3 and Jagged2 Genes in the Malay Population With Nonsyndromic Cleft Lip With or Without Cleft Palate
    Ghazali N, Rahman NA, Kannan TP, Jaafar S
    Cleft Palate Craniofac J, 2015 07;52(4):e88-94.
    PMID: 26151095 DOI: 10.1597/14-024
    OBJECTIVE: To determine the prevalence of mutations in transforming growth factor beta 3 (TGFβ3) and Jagged2 genes and their association with nonsyndromic cleft lip with or without cleft palate (CL±P) patients.

    DESIGN: Cross-sectional study on nonsyndromic CL±P and noncleft patients.

    SETTING: Reconstructive clinic and outpatient dental clinic, Hospital Universiti Sains Malaysia.

    PATIENTS: Blood samples of 96 nonsyndromic CL±P and 96 noncleft subjects.

    MAIN OUTCOME MEASURE: Prevalence and association of mutations in TGFβ3 and Jagged2 genes with nonsyndromic CL±P.

    RESULTS: Most of the nonsyndromic CL±P patients (53.1%) had left unilateral CLP. There were slightly more females (56.6%) compared with males. The prevalence of the mutations in the TGFβ3 gene was 17.7% (95% confidence interval [CI]: 9.5, 24.5) and in the Jagged2 gene was 12.5% (95% CI: 5.5, 18.5), which was higher compared with the noncleft group. For the TGFβ3 gene, there was no mutation in the coding region in either of the groups. All variants were single nucleotide polymorphisms located within the intronic flanking region. Two variants were identified (g.15812T>G and g.15966A>G) in both nonsyndromic CL±P and noncleft patients. However, the association was not significant (P > .05). Three variants (g.19779C>T, g.19547G>A, and g.19712C>T) were identified in the Jagged2 gene among nonsyndromic CL±P and noncleft patients. Only g.19712C>T showed a significant association with nonsyndromic CL±P patients (P = .039).

    CONCLUSION: g.19712C>T might play a crucial role in the development of cleft lip and palate. To the best of our knowledge, this is the first report of the mutation found within intron 13 of the Jagged2 gene among nonsyndromic CL±P Malay patients.

    Study site:Reconstructive and outpatient dental clinic, Hospital Universiti Sains Malaysia (HUSM)
    Matched MeSH terms: Introns
  17. Mutational Profiles of F8 and F9 in a Cohort of Haemophilia A and Haemophilia B Patients in the Multi-ethnic Malaysian Population
    Zahari M, Sulaiman SA, Othman Z, Ayob Y, Karim FA, Jamal R
    Mediterr J Hematol Infect Dis, 2018;10(1):e2018056.
    PMID: 30210749 DOI: 10.4084/MJHID.2018.056
    Background: Haemophilia A (HA) and Haemophilia B (HB) are X-linked blood disorders that are caused by various mutations in the factor VIII (F8) and factor IX (F9) genes respectively. Identification of mutations is essential as some of the mutations are associated with the development of inhibitors. This study is the first comprehensive study of the F8 mutational profile in Malaysia.

    Materials and methods: We analysed 100 unrelated HA and 15 unrelated HB patients for genetic alterations in the F8 and F9 genes by using the long-range PCR, DNA sequencing, and the multiplex-ligation-dependent probe amplification assays. The prediction software was used to confirm the effects of these mutations on factor VIII and IX proteins.

    Results: 44 (53%) of the severe HA patients were positive for F8 intron 22 inversion, and three (3.6%) were positive for intron one inversion. There were 22 novel mutations in F8, including missense (8), frameshift (9), splice site (3), large deletion (1) and nonsense (1) mutations. In HB patients, four novel mutations were identified including the splice site (1), small deletion (1), large deletion (1) and missense (1) mutation.

    Discussion: The mutational spectrum of F8 in Malaysian patients is heterogeneous, with a slightly higher frequency of intron 22 inversion in these severe HA patients when compared to other Asian populations. Identification of these mutational profiles in F8 and F9 genes among Malaysian patients will provide a useful reference for the early detection and diagnosis of HA and HB in the Malaysian population.

    Matched MeSH terms: Introns
  18. Variation in intronic microsatellites and exon 2 of the Plasmodium falciparum chloroquine resistance transporter gene during modification of artemisinin combination therapy in Thailand
    Seethamchai S, Buppan P, Kuamsab N, Teeranaipong P, Putaporntip C, Jongwutiwes S
    Infect Genet Evol, 2018 11;65:35-42.
    PMID: 30016713 DOI: 10.1016/j.meegid.2018.07.015
    The amino acid substitution at residue 76 of the food vacuolar transmembrane protein encoded by the chloroquine resistance transporter gene of Plasmodium falciparum (Pfcrt) is an important, albeit imperfect, determinant of chloroquine susceptibility status of the parasite. Other mutations in Pfcrt can modulate susceptibility of P. falciparum to other antimalarials capable of interfering with heme detoxification process, and may exert compensatory effect on parasite growth rate. To address whether nationwide implementation of artemisinin combination therapy (ACT) in Thailand could affect sequence variation in exon 2 and introns of Pfcrt, we analyzed 136 P. falciparum isolates collected during 1997 and 2016 from endemic areas bordering Myanmar, Cambodia and Malaysia. Results revealed 6 haplotypes in exon 2 of Pfcrt with 2 novel substitutions at c.243A > G (p.R81) and c.251A > T (p.N84I). Positive selection was observed at amino acid residues 75, 76 and 97. Four, 3, and 2 alleles of microsatellite (AT/TA) repeats occurred in introns 1, 2 and 4, respectively, resulting in 7 different 3-locus haplotypes. The number of haplotypes and haplotype diversity of exon 2, and introns 1, 2 and 4 were significantly greater among isolates collected during 2009 and 2016 than those collected during 1997 and 2008 when 3-day ACT and 2-day ACT regimens were implemented nationwide, respectively (p 
    Matched MeSH terms: Introns*
  19. Fulltext The Phosphofructokinase and Pyruvate Kinase Genes in Apis andreniformis and Apis cerana indica: Exon Intron Organisation and Evolution
    Shullia NI, Raffiudin R, Juliandi B
    Trop Life Sci Res, 2019 Jan;30(1):89-107.
    PMID: 30847035 DOI: 10.21315/tlsr2019.30.1.6
    Genes related to carbohydrate metabolism have evolved rapidly in eusocial bees, including honey bees. However, the characterisation of carbohydrate metabolism genes has not been reported in Apis andreniformis or Apis cerana indica. This study aimed to characterise phosphofructokinase (PFK) and pyruvate kinase (PK) genes in these honey bee species and to analyse the evolution of the genus Apis using these genes. This study found the first data regarding A. andreniformis PFK and PK-like nucleotide sequences. A BLAST-n algorithm-based search showed that A. andreniformis and A. c. indica PFK and PK genes were homologous with those of Apis florea and Apis cerana cerana from Korea, respectively. Multiple alignments of PFKs from five Apis species showed many exon gains and losses, but only one among the PKs. Thus, the exon-intron organisation of the PK genes may be more conserved compare with that of the PFKs. Another evolutionary pattern indicated that more nucleotide substitutions occurred in Apis' PK than PFK genes. Deduced PFK amino acid sequences revealed a PFK consensus pattern of 19 amino acids, while the deduced PK amino acid sequences were predicted to have barrel and alpha/beta domains. Based on these two metabolism-related genes, The Neighbour-joining and Maximum likelihood phylogenetic trees are congruent and revealed that the A. andreniformis and A. florea group were in the basal position. Apis mellifera, A. cerana, and Apis dorsata formed a monophyletic clade, although the positions of A. mellifera and A. dorsata were different in the nucleotide- and amino acid-based phylogenetic trees.
    Matched MeSH terms: Introns
  20. Fulltext Relevance of BRCA1 and BRCA2 variants in treating triple negative breast cancer patients
    Engku Fatimah Syairah Engku Safruddin, Wan Zainira Wan Zain, Bhavaraju, Venkata Murali Krishna, Kannan, Thirumulu Ponnuraj
    Archives of Orofacial Sciences, 2017;12(2):69-76.
    MyJurnal
    Given that the germline mutations of BRCA1 and BRCA2 confer genetic susceptibility to cancer, the
    genetic variations, polymorphisms or mutations are widely analyzed in Western countries. However, in Asian
    population, the prevalence of BRCA1 and BRCA2 polymorphisms is very limited. In Asia, breast cancer occurs in
    women early with an age of onset under 50 years. This review comprises the incidence of BRCA1 and BRCA2
    polymorphisms in the Japanese, Korean and Malaysian population. Founder mutations of BRCA1 and BRCA2
    were also compared to mark the genetic difference in these populations. The mutational analysis performed to
    analyze the entire coding region of BRCA1 and BRCA2 include the next generation sequencing and full
    sequencing of all exons and intron-exon junctions. From the diagnosis of triple negative breast cancer (TNBC)
    patients, TNBC is associated with the lack of tailored therapies and the treatment option available for TNBC
    patients is mainly chemotherapy. The poor prognosis of TNBC leads to determine the predictive biomarkers in
    order to develop treatment efficacy. This review will address the current clinical therapies available to treat TNBC
    patients.
    Matched MeSH terms: Introns
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