Displaying publications 1 - 20 of 92 in total

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  1. Fulltext Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
    Abdul Wahab SA, Yakob Y, Abdul Azize NA, Md Yunus Z, Huey Yin L, Mohd Khalid MK, et al.
    Biomed Res Int, 2016;2016:4074365.
    PMID: 27672653
    Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.
    Matched MeSH terms: Codon, Nonsense
  2. On fuzzy semantic similarity measure for DNA coding
    Ahmad M, Jung LT, Bhuiyan MA
    Comput Biol Med, 2016 Feb 1;69:144-51.
    PMID: 26773936 DOI: 10.1016/j.compbiomed.2015.12.017
    A coding measure scheme numerically translates the DNA sequence to a time domain signal for protein coding regions identification. A number of coding measure schemes based on numerology, geometry, fixed mapping, statistical characteristics and chemical attributes of nucleotides have been proposed in recent decades. Such coding measure schemes lack the biologically meaningful aspects of nucleotide data and hence do not significantly discriminate coding regions from non-coding regions. This paper presents a novel fuzzy semantic similarity measure (FSSM) coding scheme centering on FSSM codons׳ clustering and genetic code context of nucleotides. Certain natural characteristics of nucleotides i.e. appearance as a unique combination of triplets, preserving special structure and occurrence, and ability to own and share density distributions in codons have been exploited in FSSM. The nucleotides׳ fuzzy behaviors, semantic similarities and defuzzification based on the center of gravity of nucleotides revealed a strong correlation between nucleotides in codons. The proposed FSSM coding scheme attains a significant enhancement in coding regions identification i.e. 36-133% as compared to other existing coding measure schemes tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms.
    Matched MeSH terms: Codon/genetics*
  3. Application of Spiroplasma melliferum proteogenomic profiling for the discovery of virulence factors and pathogenicity mechanisms in host-associated spiroplasmas
    Alexeev D, Kostrjukova E, Aliper A, Popenko A, Bazaleev N, Tyakht A, et al.
    J Proteome Res, 2012 Jan 1;11(1):224-36.
    PMID: 22129229 DOI: 10.1021/pr2008626
    To date, no genome of any of the species from the genus Spiroplasma has been completely sequenced. Long repetitive sequences similar to mobile units present a major obstacle for current genome sequencing technologies. Here, we report the assembly of the Spiroplasma melliferum KC3 genome into 4 contigs, followed by proteogenomic annotation and metabolic reconstruction based on the discovery of 521 expressed proteins and comprehensive metabolomic profiling. A systems approach allowed us to elucidate putative pathogenicity mechanisms and to discover major virulence factors, such as Chitinase utilization enzymes and toxins never before reported for insect pathogenic spiroplasmas.
    Matched MeSH terms: Codon
  4. Fulltext Characterisation of full-length cDNA sequences provides insights into the Eimeria tenella transcriptome
    Amiruddin N, Lee XW, Blake DP, Suzuki Y, Tay YL, Lim LS, et al.
    BMC Genomics, 2012 Jan 13;13:21.
    PMID: 22244352 DOI: 10.1186/1471-2164-13-21
    BACKGROUND: Eimeria tenella is an apicomplexan parasite that causes coccidiosis in the domestic fowl. Infection with this parasite is diagnosed frequently in intensively reared poultry and its control is usually accorded a high priority, especially in chickens raised for meat. Prophylactic chemotherapy has been the primary method used for the control of coccidiosis. However, drug efficacy can be compromised by drug-resistant parasites and the lack of new drugs highlights demands for alternative control strategies including vaccination. In the long term, sustainable control of coccidiosis will most likely be achieved through integrated drug and vaccination programmes. Characterisation of the E. tenella transcriptome may provide a better understanding of the biology of the parasite and aid in the development of a more effective control for coccidiosis.

    RESULTS: More than 15,000 partial sequences were generated from the 5' and 3' ends of clones randomly selected from an E. tenella second generation merozoite full-length cDNA library. Clustering of these sequences produced 1,529 unique transcripts (UTs). Based on the transcript assembly and subsequently primer walking, 433 full-length cDNA sequences were successfully generated. These sequences varied in length, ranging from 441 bp to 3,083 bp, with an average size of 1,647 bp. Simple sequence repeat (SSR) analysis identified CAG as the most abundant trinucleotide motif, while codon usage analysis revealed that the ten most infrequently used codons in E. tenella are UAU, UGU, GUA, CAU, AUA, CGA, UUA, CUA, CGU and AGU. Subsequent analysis of the E. tenella complete coding sequences identified 25 putative secretory and 60 putative surface proteins, all of which are now rational candidates for development as recombinant vaccines or drug targets in the effort to control avian coccidiosis.

    CONCLUSIONS: This paper describes the generation and characterisation of full-length cDNA sequences from E. tenella second generation merozoites and provides new insights into the E. tenella transcriptome. The data generated will be useful for the development and validation of diagnostic and control strategies for coccidiosis and will be of value in annotation of the E. tenella genome sequence.

    Matched MeSH terms: Codon
  5. Fulltext Griscelli syndrome
    Ariffin H, Geikowski A, Chin TF, Chau D, Arshad A, Abu Bakar K, et al.
    Med J Malaysia, 2014 Aug;69(4):193-4.
    PMID: 25500851 MyJurnal
    We report a case of Griscelli Syndrome (GS). Our patient initially presented with a diagnosis of haemophagocytic lymphistiocytosis (HLH). Subsequent microscopic analysis of the patient's hair follicle revealed abnormal distribution of melanosomes in the shaft, which is a hallmark for GS. Analysis of RAB27A gene in this patient revealed a homozygous mutation in exon 6, c.550C>T, p.R184X . This nonsense mutation causes premature truncation of the protein resulting in a dysfunctional RAB27A. Recognition of GS allows appropriate institution of therapy namely chemotherapy for HLH and curative haemotopoeitic stem cell transplantation.
    Matched MeSH terms: Codon, Nonsense
  6. Therapeutic Suppression of Nonsense Mutation: An Emerging Target in Multiple Diseases and Thrombotic Disorders
    Asiful Islam M, Alam F, Kamal MA, Gan SH, Wong KK, Sasongko TH
    Curr Pharm Des, 2017;23(11):1598-1609.
    PMID: 27875971 DOI: 10.2174/1381612823666161122142950
    Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i.e. translational readthrough) regimens. In this review, we highlighted different treatment strategies of PTC targeting readthrough therapeutics including the use of aminoglycosides, ataluren (formerly known as PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic disorders are a group of disease with major burdens worldwide, 19 potential genes containing a total of 705 PTCs that cause 21 thrombotic disorders have been listed based on the data reanalysis from the 'GeneCards® - Human Gene Database' and 'Human Gene Mutation Database' (HGMD®). These PTC-containing genes can be potential targets amenable for different readthrough therapeutic strategies in the future.
    Matched MeSH terms: Codon, Nonsense/drug effects*; Codon, Nonsense/genetics*
  7. Fulltext Preliminary study on association of beta2-adrenergic receptor polymorphism with hypertension in hypertensive subjects attending Balok Health Centre, Kuantan
    Atia AE, Norsidah K, Nor Zamzila A, Rafidah Hanim M, Samsul D, Aznan MA, et al.
    Med J Malaysia, 2012 Feb;67(1):25-30.
    PMID: 22582545
    Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.
    Matched MeSH terms: Codon
  8. Fulltext Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome
    Baharin MF, Kader Ibrahim SB, Yap SH, Abdul Manaf AM, Mat Ripen A, Dhaliwal JS
    Malays J Pathol, 2015 Aug;37(2):153-8.
    PMID: 26277674 MyJurnal
    The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.
    Matched MeSH terms: Codon, Nonsense
  9. Episodic positive selection in the Cam734 haplotype and low prevalence of the A144F mutation in Plasmodium falciparum chloroquine resistance transporter gene among Thai isolates
    Buppan P, Seethamchai S, Kuamsab N, Jongwutiwes S, Putaporntip C
    Trop Biomed, 2018 Dec 01;35(4):861-871.
    PMID: 33601836
    Chloroquine resistance transporter of Plasmodium falciparum (PfCRT) is a food vacuolar transmembrane protein that mediates susceptibility of the parasite to chloroquine. A mutation at K76T of the Pfcrt gene is a key determinant for chloroquine resistance phenotype. In the absence of drug pressure, in vitro growth rate of chloroquine-resistance parasites was outcompeted by wild-type parasites unless intragenic compensatory mutations occurred. Chloroquine-resistant P. falciparum bearing the Cam734 haplotype known to circulate in endemic areas of Cambodia bordering Thailand contains 9 mutations in Pfcrt and exhibits both chloroquine resistance and comparable growth rate to the chloroquine-sensitive 3D7 strain. To analyze the evolution of the Cam734 haplotype, codon-based analysis was performed by using the mixed effects model of evolution (MEME), branch-site random effects likelihood (BR-REL) and other related methods. Results revealed that the Cam734 haplotype has evolved distinctively from other known mutant haplotypes including the most common Dd2 haplotype in Southeast Asia. Evidence of episodic positive selection was detected at codon 144, characterized by c.[430G>T; 431C>T] (p.A144F), known to be indispensable for both chloroquine resistance and restoration of growth rate of the parasites. To survey the prevalence of mutations at codons 76 and 144 in Pfcrt among Thai isolates, restriction fragment analysis of 548 P. falciparum isolates collected from six endemic provinces of Thailand during 1991 and 2016 was performed. The 144F Pfcrt mutant was detected in 7 (1.28%) isolates. All Thai isolates analyzed herein harbored a mutation at codon 76 whilst the wild-type parasite was not found. The low prevalence of isolates bearing the mutation 144F in PfCRT could imply little or lack of survival advantage of this mutant in endemic areas of Thailand where the wild-type parasites seem to be absent or extremely rare.
    Matched MeSH terms: Codon
  10. Fulltext Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family
    Ch'ng GS, An SS, Bae SO, Bagyinszky E, Kim S
    Neuropsychiatr Dis Treat, 2015;11:2315-22.
    PMID: 26396515 DOI: 10.2147/NDT.S86334
    Alzheimer's disease (AD) is the most common form of dementia, which can be categorized into two main forms: early onset AD and late onset AD. The genetic background of early onset AD is well understood, and three genes, the APP, PSEN1, and PSEN2 have been identified as causative genes. In the current study, we tested three siblings from Malaysia who were diagnosed with early onset dementia, as well as their available family members. The family history was positive as their deceased father was similarly affected. Patients were tested for mutations in APP, PSEN1, PSEN2, and PRNP. A novel variant, E280K, was discovered in exon 8 of PSEN1 in the three siblings. In silico analyses with SIFT, SNAP, and PolyPhen2 prediction tools and three-dimensional modeling were performed, and the results suggested that the mutation is probably a pathogenic variant. Two additional pathogenic mutations were previously been described for codon 280, E280A, and E280G, which could support the importance of the E280 residue in the PS1 protein contributing to the pathogenic nature of E280K. Additional ten family members were screened for the E280K mutation, and all of them were negative. Six of them presented with a variety of neuropsychiatric symptoms, including learning disabilities, epilepsy, and schizophrenia, while four family members were asymptomatic. A novel PRNP G127S mutation was found in a step-niece of the three siblings harboring the PSEN1 E280K mutation. In silico predictions for PRNP G127S mutation suggested that this might be possibly a damaging variant. Additional studies to characterize PRNP G127S would be necessary to further understand the effects of this mutation.
    Matched MeSH terms: Codon
  11. Fulltext Analysis of codon usage patterns and influencing factors in Nipah virus
    Chakraborty S, Deb B, Barbhuiya PA, Uddin A
    Virus Res, 2019 04 02;263:129-138.
    PMID: 30664908 DOI: 10.1016/j.virusres.2019.01.011
    Codon usage bias (CUB) is the unequal usage of synonymous codons of an amino acid in which some codons are used more often than others and is widely used in understanding molecular biology, genetics, and functional regulation of gene expression. Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes fatal disease in both humans and animals. NiV was first identified during an outbreak of a disease in Malaysia in 1998 and then occurred periodically since 2001 in India, Bangladesh, and the Philippines. We used bioinformatics tools to analyze the codon usage patterns in a genome-wide manner among 11 genomes of NiV as no work was reported yet. The compositional properties revealed that the overall GC and AT contents were 41.96 and 58.04%, respectively i.e. Nipah virus genes were AT-rich. Correlation analysis between overall nucleotide composition and its 3rd codon position suggested that both mutation pressure and natural selection might influence the CUB across Nipah genomes. Neutrality plot revealed natural selection might have played a major role while mutation pressure had a minor role in shaping the codon usage bias in NiV genomes.
    Matched MeSH terms: Codon*
  12. Induction of a putative metallothionein gene in the blood cockle, Anadara granosa, exposed to cadmium
    Chan MK, Othman R, Zubir D, Salmijah S
    Comp Biochem Physiol C Toxicol Pharmacol, 2002 Feb;131(2):123-32.
    PMID: 11879780
    The relationship between a putative metallothionein gene (MT) and exposure to cadmium (Cd) in blood cockles (Anadara granosa) is reported. In a 96-h dose-response experiment, mortality of cockles was found to proportionately increase in the range of 0.2-5.0 mg/l Cd with a calculated LC(50) of 2.94 mg/l. Exposure to 0.25 mg/l Cd for 16 days caused significant increases (P<0.05) in Cd concentrations in whole tissues, gills and hepatopancreas, and the accumulation of Cd in these tissues increased with the duration of exposure. Two cDNA libraries constructed using the hepatopancreas from control and Cd-treated cockles gave titres of 5.62 x 10(5) and 1.94 x 10(5) pfu/microg vector, respectively. A putative MT gene, AnaMT, of 510 nucleotides in length, was isolated from the treated cDNA library using a heterologous probe MT20 from the blue mussel, Mytilus edulis. Northern analyses using AnaMT as a probe indicated low expression of the MT mRNA in control animals. In cockles treated with 0.25 mg/l Cd for 4 days, MT mRNA level increased to approximately 168%, but declined to 108% at day 8. After 12 and 16 days of Cd treatment, expression of the MT gene was 138% and 187%, respectively, compared to the controls. These observations suggest that induction of the MT gene by a sublethal dose of Cd is rapid, occurring within 4 days of treatment.
    Matched MeSH terms: Codon
  13. Complete nucleotide sequences of Nipah virus isolates from Malaysia
    Chan YP, Chua KB, Koh CL, Lim ME, Lam SK
    J Gen Virol, 2001 Sep;82(Pt 9):2151-5.
    PMID: 11514724
    We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.
    Matched MeSH terms: Codon
  14. Fulltext Hepatitis B Virus Genotypes and Mutations Affecting HBeAg Production: A Malaysian Perspective
    Cheek, Ken Lim, So, Har Ton
    Medicine & Health, 2007;2(1):1-25.
    MyJurnal
    Infection by hepatitis B virus (HBV) is a major global health-care problem. HBV is an accepted factor in the elevated risks for liver disease such as cirrhosis and development of hepatocellular carcinoma. This problem is particularly prevalent in the Asia-Pacific region which includes Malaysia. During infection, the hepatitis B e antigen (HBeAg) is produced in the hosts. This antigen is an important serological marker for diagnosing chronic hepatitis B. Seroconversion to anti-body (anti-HBe) corresponds to the improvement of disease prognosis. However, certain mutations such as the core promoter dual mutations (A1762G1764→T1762A1764), the codon 15 variants (C1858/ T1858) and the precore stop codon mutations (TGG→TAG) can affect the HBeAg expression. This has diagnostic and clinical implications. Besides that, the HBV can be grouped into eight genotypes (A to H). Moreover, genotypic subtypes and recombinants have been observed as well. Studies have observed that these can differ in their affiliations with the mutations above as well as with disease prognosis.
    Matched MeSH terms: Codon, Terminator
  15. Fulltext Mutations causing streptomycin resistance in Mycobacterium tuberculosis isolates of Sabah
    Cheronie Shely Stanis, Myo Thura Zaw, Zainal Arifin Mustapha, Nor Amalina Emran, Richard Avoi, Jiloris Frederick Dony, et al.
    Malaysian Journal of Medicine and Health Sciences, 2019;15(106):22-22.
    MyJurnal
    Introduction: Tuberculosis (TB) still remains a public health problem worldwide and the emergence of drug resistant TB (DR-TB) has worsened the situation as it is difficult and expensive to treat. The characterization of the genetic mutations underlying streptomycin resistance may be helpful in developing rapid detection methods which may guide clinicians in making therapeutic decisions. The aim of this study is to detect mutations causing streptomycin (STR) resistance in Mycobacterium tuberculosis isolates from Sabah. Methods: Susceptibility testing was carried out in MGIT system for 42 Mycobacterium tuberculosis clinical isolates. The drug resistant isolates were subject to whole genome sequencing and in-silico analysis was performed to detect the mutations in the sequence of the rpsL gene known to confer resistance to anti-tuberculous drugs. Results: Of the 42 positive isolates, 27 (64.3%) are shown to be susceptible towards first line drugs (FLDs) while 15 (35.7%) isolates were mono- and multiple resistant to the FLDs. Our findings reveal that the isolate 145 possess mutations at codon 43 within rpsL gene with amino acid change A to G (K43R). Conclusion: Findings from this study enable us to expand our knowledge of mutations causing drug resistance in Mycobacterium tuberculosis and the point mutations, which can be used as the potential marker for detection of drug resistant isolates.
    Matched MeSH terms: Codon
  16. Fulltext Denaturing gradient-gel electrophoresis screening of familial defective apolipoprotein B-100 in a mixed Asian cohort: two cases of arginine3500-->tryptophan mutation associated with a unique haplotype
    Choong ML, Koay ES, Khoo KL, Khaw MC, Sethi SK
    Clin Chem, 1997 Jun;43(6 Pt 1):916-23.
    PMID: 9191540
    The Arg-to-Trp substitution at codon 3500 in the apolipoprotein (apo) B-100 gene is established as a cause of familial defective apo B-100 (FDB), a functional mutation, resulting in reduced LDL receptor binding and manifest hypercholesterolemia. In a search for similar mutations in 163 Malaysians, we screened the putative receptor-binding region (codons 3456-3553) of the apo B-100 gene by PCR amplification and denaturing gradient-gel electrophoresis. Four single-base mutations were detected and confirmed by DNA sequencing. Two females, a Chinese and a Malay, had the same CGG3500-->TGG mutation, resulting in an Arg3500-to-Trp substitution. This is the second published report of such an independent mutation involving the same codon as the established Arg3500-to-Gln mutation. The two other mutations detected, CTT3517-->CTG and GCC3527-->GCT, resulted in degenerate codons with no amino acid substitutions. All four mutations were associated with a unique apo B haplotype, different from those found in Caucasian FDB patients but concurring with that previously reported for two other Asians with FDB.
    Matched MeSH terms: Codon
  17. Fulltext Mutant Allele-Specific CRISPR Disruption in DYT1 Dystonia Fibroblasts Restores Cell Function
    Cruz L, György B, Cheah PS, Kleinstiver BP, Eimer WA, Garcia SP, et al.
    Mol Ther Nucleic Acids, 2020 Sep 04;21:1-12.
    PMID: 32502938 DOI: 10.1016/j.omtn.2020.05.009
    Most individuals affected with DYT1 dystonia have a heterozygous 3-bp deletion in the TOR1A gene (c.907_909delGAG). The mutation appears to act through a dominant-negative mechanism compromising normal torsinA function, and it is proposed that reducing mutant torsinA may normalize torsinA activity. In this study, we used an engineered Cas9 variant from Streptococcus pyogenes (SpCas9-VRQR) to target the mutation in the TOR1A gene in order to disrupt mutant torsinA in DYT1 patient fibroblasts. Selective targeting of the DYT1 allele was highly efficient with most common non-homologous end joining (NHEJ) edits, leading to a predicted premature stop codon with loss of the torsinA C terminus (delta 302-332 aa). Structural analysis predicted a functionally inactive status of this truncated torsinA due to the loss of residues associated with ATPase activity and binding to LULL1. Immunoblotting showed a reduction of the torsinA protein level in Cas9-edited DYT1 fibroblasts, and a functional assay using HSV infection indicated a phenotypic recovery toward that observed in control fibroblasts. These findings suggest that the selective disruption of the mutant TOR1A allele using CRISPR-Cas9 inactivates mutant torsinA, allowing the remaining wild-type torsinA to exert normal function.
    Matched MeSH terms: Codon, Nonsense
  18. Existence of two emm-like "mrp" and "emm" genes in the mga regulon of the Streptococcus pyogenes strain ST4547
    Eshaghi M, Ali AM, Jamal F, Yusoff K
    J. Biochem. Mol. Biol. Biophys., 2002 Feb;6(1):23-8.
    PMID: 12186779
    Streptococcus pyogenes ST4547 is an opacity factor negative strain, which has been recently reported as a new emm type from Malaysia. Nucleotide sequencing of the mga regulon of this strain showed the existence of two emm-like genes. The emm gene located upstream of the scpA gene comprises 1305 nucleotides encoding the putative precursor M protein of 435 amino acids in length with an M(r) of 49 kDa. or a predicted mature protein of 394 amino acids with an M(r) of 44.8 kDa. Another gene mrpST4547 was located upstream of the emm gene and downstream of the mga gene. The sequence of this mrp gene comprises 1167 nucleotides encoding a predicted protein of 388 amino acids in length with an M(r) of 42.2 kDa. or a predicted mature protein of 347 amino acids with an M(r) of 37.9 kDa. The mga regulon of strain ST4547 has a mosaic structure comprising segments, which originated from different OF positive and OF negative strains. The sequences flanking the hyper-variable and C repeats of the emmST4547 gene showed high similarity to corresponding regions in the mga regulon of OF positive strains notably M15, M4, M22 and M50. In contrast, the sequence within the hyper-variable and C repeat regions of the emmST4547 gene revealed high similarity to equivalent regions in the OF negative strains. These data indicates that horizontal transfer of emm-like gene could have occurred between OF positive and OF negative strains resulting in architectural divergence in the mga regulon.
    Matched MeSH terms: Codon
  19. Fulltext Cytosolic DNA sensing through cGAS and STING is inactivated by gene mutations in pangolins
    Fischer H, Tschachler E, Eckhart L
    Apoptosis, 2020 08;25(7-8):474-480.
    PMID: 32533513 DOI: 10.1007/s10495-020-01614-4
    The release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a "natural knockout" model of cGAS. Comparative genomics of phylogenetically diverse mammalian species showed that cGAS and its interaction partner Stimulator of Interferon Genes (STING) have been inactivated by mutations in the Malayan pangolin whereas other mammals retained intact copies of these genes. The coding sequences of CGAS and STING1 are also disrupted by premature stop codons and frame-shift mutations in Chinese and tree pangolins, suggesting that expression of these genes was lost in a common ancestor of all pangolins that lived more than 20 million years ago. AIM2 is retained in a functional form in pangolins whereas it is inactivated by mutations in carnivorans, the phylogenetic sister group of pangolins. The deficiency of cGAS and STING points to the existence of alternative mechanisms of controlling cytoplasmic DNA-associated cell damage and viral infections in pangolins.
    Matched MeSH terms: Codon, Terminator
  20. Molecular basis of beta-thalassemia in the Maldives
    Furuumi H, Firdous N, Inoue T, Ohta H, Winichagoon P, Fucharoen S, et al.
    Hemoglobin, 1998 Mar;22(2):141-51.
    PMID: 9576331
    We have systematically analyzed beta-thalassemia genes using polymerase chain reaction-related techniques, dot-blot hybridization with oligonucleotide probes, allele specific-polymerase chain reaction, and sequencing of amplified DNA fragments from 41 unrelated patients, including 37 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four different beta-thalassemia mutations were detected in 78 alleles. These are the IVS-I-5 (G-->C), codon 30 (AGG-->ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G-->A), and codons 41/42 (-TTCT) mutations. The distribution of the beta-thalassemia mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G-->C) mutation, 12 (15.4%) with the codon 30 (AGG-->ACG) mutation, seven (9%) with the IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mutation. The first three mutations account for 98.7% of the total number of beta-thalassemia chromosomes studied. These mutations are clustered in the region spanning 6 bp around the junction of exon 1 and the first intervening sequence of the beta-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and frameworks of chromosomes bearing each beta-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.
    Matched MeSH terms: Codon/genetics
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