Displaying publications 141 - 160 of 587 in total

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  1. Genetics and polymorphism of a sex-linked gene in the grasshopper, Oxya japonica japonica (Orthoptera: Acrididae: Oxyinae)
    Chan KL, Yushayati Y, Guaneswaran P
    Biochem Genet, 1991 Apr;29(3-4):203-6.
    PMID: 1830472
    Matched MeSH terms: Phenotype
  2. alpha1-Antitrypsin polymorphism in Malaysian Macaca irus
    Kueppers F, Ganesan J
    Biochem Genet, 1977 Oct;15(9-10):817-23.
    PMID: 412492
    alpha1-Antitrypsin types were determined in 200 individual specimens of Malaysian Macaca irus. We found the pattern B in 76 samples, BC in 116, and C in 8. Assuming that these patterns are determined by codominant alleles at one locus, this distribution constitutes a significant (P less than 0.001) deviation from Hardy-Weinberg equilibrium, because of an excess of BC and low prevalence of C. We found no clear evidence for the presence of alpha1-antitrypsin deficiency comparable to the situation in man.
    Matched MeSH terms: Phenotype
  3. Genetics of glucosephosphate isomerase in Aedes togoi (Diptera: Culicidae)
    Yong HS, Cheong WH, Mak JW, Chiang GL, Chan KL, Dhaliwal SS
    Biochem Genet, 1980 Oct;18(9-10):939-45.
    PMID: 7225086
    The genetics of glucosephosphate isomerase (E.C. 5.3.1.9) in two strains (Malaysian and Taiwan) of Aedes togoi is reported. Three electrophoretic phenotypes were presented in both sexes. The zymogram patterns were identical in both strains of A. togoi. The phenotypes were governed by a pair of codominant alleles. The allele frequency of the slow-moving band was 0.63 in the Malaysian strain adn was 0,86 and 0.82 in F161 and F169 generations, respectively, of the Taiwan strain. The sample studied was in good accord with Hardy-Weinberg expectation.
    Matched MeSH terms: Phenotype
  4. Fulltext Non-tenera Contamination and the Economic Impact of SHELL Genetic Testing in the Malaysian Independent Oil Palm Industry
    Ooi LC, Low ET, Abdullah MO, Nookiah R, Ting NC, Nagappan J, et al.
    Front Plant Sci, 2016;7:771.
    PMID: 27446094 DOI: 10.3389/fpls.2016.00771
    Oil palm (Elaeis guineensis) is the most productive oil bearing crop worldwide. It has three fruit forms, namely dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), which are controlled by the SHELL gene. The fruit forms exhibit monogenic co-dominant inheritance, where tenera is a hybrid obtained by crossing maternal dura and paternal pisifera palms. Commercial palm oil production is based on planting thin-shelled tenera palms, which typically yield 30% more oil than dura palms, while pisifera palms are female-sterile and have little to no palm oil yield. It is clear that tenera hybrids produce more oil than either parent due to single gene heterosis. The unintentional planting of dura or pisifera palms reduces overall yield and impacts land utilization that would otherwise be devoted to more productive tenera palms. Here, we identify three additional novel mutant alleles of the SHELL gene, which encode a type II MADS-box transcription factor, and determine oil yield via control of shell fruit form phenotype in a manner similar to two previously identified mutant SHELL alleles. Assays encompassing all five mutations account for all dura and pisifera palms analyzed. By assaying for these variants in 10,224 mature palms or seedlings, we report the first large scale accurate genotype-based determination of the fruit forms in independent oil palm planting sites and in the nurseries that supply them throughout Malaysia. The measured non-tenera contamination rate (10.9% overall on a weighted average basis) underscores the importance of SHELL genetic testing of seedlings prior to planting in production fields. By eliminating non-tenera contamination, comprehensive SHELL genetic testing can improve sustainability by increasing yield on existing planted lands. In addition, economic modeling demonstrates that SHELL gene testing will confer substantial annual economic gains to the oil palm industry, to Malaysian gross national income and to Malaysian government tax receipts.
    Matched MeSH terms: Phenotype
  5. Genomic diversity and genome-wide association analysis related to yield and fatty acid composition of wild American oil palm
    Ithnin M, Vu WT, Shin MG, Suryawanshi V, Sherbina K, Zolkafli SH, et al.
    Plant Sci, 2021 Mar;304:110731.
    PMID: 33568284 DOI: 10.1016/j.plantsci.2020.110731
    Existing Elaeis guineensis cultivars lack sufficient genetic diversity due to extensive breeding. Harnessing variation in wild crop relatives is necessary to expand the breadth of agronomically valuable traits. Using RAD sequencing, we examine the natural diversity of wild American oil palm populations (Elaeis oleifera), a sister species of the cultivated Elaeis guineensis oil palm. We genotyped 192 wild E. oleifera palms collected from seven Latin American countries along with four cultivated E. guineensis palms. Honduras, Costa Rica, Panama and Colombia palms are panmictic and genetically similar. Genomic patterns of diversity suggest that these populations likely originated from the Amazon Basin. Despite evidence of a genetic bottleneck and high inbreeding observed in these populations, there is considerable genetic and phenotypic variation for agronomically valuable traits. Genome-wide association revealed several candidate genes associated with fatty acid composition along with vegetative and yield-related traits. These observations provide valuable insight into the geographic distribution of diversity, phenotypic variation and its genetic architecture that will guide choices of wild genotypes for crop improvement.
    Matched MeSH terms: Phenotype
  6. Fulltext Hypothetical Protein BPSL3393 of Burkholderia pseudomallei is Involved in Ethanolamine Catabolism
    Luan OG, Yam H, Samian R, Wajidi MFF, Mahadi NM, Mohamad S, et al.
    Trop Life Sci Res, 2017 Jul;28(2):57-74.
    PMID: 28890761 MyJurnal DOI: 10.21315/tlsr2017.28.2.5
    Burkholderia pseudomallei is a soil-dwelling bacterium that causes a globally emerging disease called melioidosis. Approximately one third of the in silico annotated genes in its genome are classified as hypothetical genes. This group of genes is difficult to be functionally characterised partly due to the absence of noticeable phenotypes under conventional laboratory settings. A bioinformatic survey of hypothetical genes revealed a gene designated as BPSL3393 that putatively encodes a small protein of 11 kDA with a CoA binding domain. BPSL3393 is conserved in all the B. pseudomallei genomes as well as various in other species within the genus Burkholderia. Taking into consideration that CoA plays a ubiquitous metabolic role in all life forms, characterisation of BPSL3393 may uncover a previously over-looked metabolic feature of B. pseudomallei. The gene was deleted from the genome using a double homologous recombination approach yielding a null mutant. The BPSL3393 mutant showed no difference in growth rate with the wild type under rich and minimal growth conditions. An extensive metabolic phenotyping test was performed involving 95 metabolic substrates. The deletion mutant of BPSL3393 was severely impaired in its ethanolamine metabolism. The growth rate of the mutant was attenuated when ethanolamine was used as the sole carbon source. A transcriptional analysis of the ethanolamine metabolism genes showed that they were down-regulated in the BPSL3393 mutant. This seemed to suggest that BPSL3393 functions as a positive regulator for ethanolamine metabolism.
    Matched MeSH terms: Phenotype
  7. Sexual selection predicts the persistence of populations within altered environments
    Parrett JM, Mann DJ, Chung AYC, Slade EM, Knell RJ
    Ecol Lett, 2019 Oct;22(10):1629-1637.
    PMID: 31353816 DOI: 10.1111/ele.13358
    The effect of sexual selection on species persistence remains unclear. The cost of bearing ornaments or armaments might increase extinction risk, but sexual selection can also enhance the spread of beneficial alleles and increase the removal of deleterious alleles, potentially reducing extinction risk. Here we investigate the effect of sexual selection on species persistence in a community of 34 species of dung beetles across a gradient of environmental disturbance ranging from old growth forest to oil palm plantation. Horns are sexually selected traits used in contests between males, and we find that both horn presence and relative size are strongly positively associated with species persistence and abundance in altered habitats. Testes mass, an indicator of post-copulatory selection, is, however, negatively linked with the abundance of species within the most disturbed habitats. This study represents the first evidence from a field system of a population-level benefit from pre-copulatory sexual selection.
    Matched MeSH terms: Phenotype
  8. Fulltext Relative proteome quantification of alpha, beta, gamma and delta globin chains in early eluting peaks of Bio-Rad variant II® CE-HPLC of hemoglobin from healthy and beta-thalassemia subjects in Malaysia
    Abdullah UYH, Ibrahim HM, Jassim HM, Salleh MZ, Kek TL, Fakhruzzaman Bin Noorizhab MN, et al.
    Biochem Biophys Rep, 2019 Jul;18:100635.
    PMID: 31061897 DOI: 10.1016/j.bbrep.2019.100635
    This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome.
    Matched MeSH terms: Phenotype
  9. Characterization of resistance to pirimiphos-methyl (an organophosphate insecticide) in Culex pipiens pipiens (Diptera: Culicidae) from Northern and Southern Tunisia
    Tabbabi A, Daaboub J, Ben-Cheikh R, Laamari A, Feriani M, Boubaker C, et al.
    Trop Biomed, 2018 Dec 01;35(4):872-879.
    PMID: 33601837
    Despite the public health importance of Culex pipiens pipiens, their resistance to pirimiphos-methyl insecticides has not been explored enough. Late third and early fourth larvae of Culex pipiens pipiens were collected from three localities between 2003 and 2005 in Northern and Southern Tunisia. All bioassays were carried out using pirimiphosmethyl and propoxur insecticides. Populations of Culex pipiens pipiens were susceptible, moderate and resistant to pirimiphos-methyl insecticide. Resistance to this compound ranged from 2.62 in sample # 2 to 19.9 in sample # 1. The moderate resistance (5.25) was recorded in sample # 3. Synergist's tests showed that the resistance to pirimiphos-methyl was not affected by detoxification enzymes. However, biochemical assays showed the involvement of both metabolic (esterases) and target site (insensitive acetylcholinesterase) resistance mechanisms. The highest frequencies of the resistant phenotypes ([RS] and [RR]) (<0.74) were detected in the most resistant samples (#1). Four esterases enzymes including C1 encoded by the Est-1 locus and three esterases encoded by the Ester super locus: A2-B2, A4-B4 (or A5-B5, which has the same electrophoretic mobility) and B12 were detected. The highest (0.61) and the lowest (0.22) frequencies of these esterases were recorded in samples # 1 (Sidi Hcine) and # 2 (El Fahs) which recorded the highest and the lowest level of resistance, respectively. Monitoring of insecticide resistance should be evaluated regularly for management of vector control.
    Matched MeSH terms: Phenotype
  10. Multiple resistance mechanisms associated with low pirimifos-methyl resistance in Culex pipiens pipiens in three populations of Tunisia
    Tabbabi A, Daaboub J, Laamari A, Ben-Cheikh R, Feriani M, Boubaker C, et al.
    Trop Biomed, 2018 Dec 01;35(4):1107-1114.
    PMID: 33601857
    The aim of this study was to evaluate the resistance status of Culex pipiens pipiens to pirimiphos-methyl insecticide. Three field populations of mosquitoes were collected from Tunisia and analyzed in laboratory. The samples studied showed low level of resistance not exceeding 5-folds. The low resistance recorded is particularly interesting, because it leaves a range of tools useable by vector control services. Both metabolic and target-site resistance mechanisms were identified. Different esterases of high activity including A2-B2, A4-B4 (and/or A5-B5) and B12 were observed in studied field samples using starch electrophoresis although opposite results were found using synergists tests on samples # 1 and 3. The polymorphism of AChE1 (Acetylcholinesterase) was analyzed and three phenotypes were detected: susceptible (ACHE1S, phenotype [SS]), resistant (ACHE1R, phenotype [RR]), and heterozygous (phenotype [RS]) of ACHE1. The resistance of Culex pipiens pipiens to pirimiphos-methyl remains low although the occurrences of multiple resistance mechanisms are able to confer high resistance levels to organophosphate insecticides. Therefore, continuous monitoring of resistance is fundamental for rational use of insecticides and mosquito control programs.
    Matched MeSH terms: Phenotype
  11. 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: Phenotype
  12. Fulltext Fatal Delayed Haemolytic Transfusion Reaction and Hyperhaemolysis Syndrome in a Pregnant Woman with Sickle Cell Anaemia
    Asnawi AW, Sathar J, Mohamed R, Deraman R, Kumaran S, Hamid SS, et al.
    Indian J Hematol Blood Transfus, 2016 Jun;32(Suppl 1):251-3.
    PMID: 27408406 DOI: 10.1007/s12288-014-0495-9
    Clinical manifestations of sickle cell disease (SCD) arise from the tendency of the sickle haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape. Sickle cell crisis is a devastating complication that may occur in patients with SCD. If not managed properly permanent organ damage and even death may be the final outcome. A case of a 32-year-old Nigerian lady, Gravida 1 Para 0 in her first trimester, with SCD who developed signs and symptoms of delayed haemolytic transfusion reaction after receiving packed red cell transfusion is demonstrated. Multiple red cell alloantibodies were detected in the patient's plasma; anti-Fy a, anti-Jk b and anti-E. The patient miscarriaged and succumbed to complications of hyperhaemolysis with delayed haemolytic transfusion reaction, acute chest syndrome and renal failure. There is an urgent need for mandatory red cell antibody screen and identification especially in high-risk cases. Prevention of alloimmunization by supplying phenotype-specific red cells is also required.
    Matched MeSH terms: Phenotype
  13. Fulltext Phenotypic MicroArray (PM) profiles (carbon sources and sensitivity to osmolytes and pH) of Campylobacter jejuni ATCC 33560 in response to temperature
    Tang, J.Y.H., Carlson, J., Mohamad Ghazali, F., Saleha, A.A., Nishibuchi, M., Nakaguchi, Y., et al.
    International Food Research Journal, 2010;17(4):837-844.
    MyJurnal
    The present study aimed to provide an insight of C. jejuni ATCC 33560 phenotype profiles (carbon sources and sensitivity to osmolytes and pH) using Phenotypic MicroArray (PM) system in response to optimal and suboptimal temperature. C. jejuni ATCC 33560 showed utilization carbon sources from amino acids and carboxylates but not from sugars. C. jejuni ATCC 33560 is sensitive to NaCl at 2% and above but showed survival in a wide range of food preservatives (sodium lactate, sodium phosphate, sodium benzoate, ammonium sulphate and sodium nitrate). When incubated at suboptimal temperature, no phenotype loss was observed in carbon source plates. Phenotype loss of C. jejuni ATCC 33560 was observed in sodium chloride (1%), sodium sulphate (2-3%), sodium formate (1%), sodium lactate (7-12%), sodium phosphate pH7 (100mM and 200mM), ammonium sulphate pH8 (50mM), sodium nitrate (60mM, 80mM and 100mM), sodium nitrite (10mM), and growth in pH5. The phenotypic profile from present study will provide a better insight related to survival of C. jejuni ATCC 33560.
    Matched MeSH terms: Phenotype
  14. Fulltext Elevated expression of CD151 gene in estrogen receptor and progesterone receptor positive breast carcinoma
    Ivyna Bong, P.N., Zubaidah, Z., Rohaizak, M., Naqiyah, I., Noor Hisham, A., Sharifah, N.A., et al.
    Medicine & Health, 2011;6(1):33-40.
    MyJurnal
    The tetraspanin gene, CD151 is involved in various tumour cell progression and metastasis. Its expression is increased in high grade, estrogen receptor negative and c-erbB-2 positive breast cancer. However, the biological function and expression phenotype among different tumour status, estrogen receptor (ER) status, progesterone receptor (PR) status and c-erbB-2 expression in multi-ethnic Malaysian breast cancer patients has not been well investigated. We used quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to measure the CD151 gene expression in 45 breast cancers. Our preliminary results revealed that CD151 expression is significantly higher in ER positive and PR positive breast cancers at 95% and 99% confidence intervals, respectively. In contrast, there is no significant correlation between CD151 expression and tumour grades or c-erbB-2 status at 95% confidence interval level. Our preliminary findings suggested that CD151 may be involved in the estrogen responsive pathways. CD151 could be a potential prognostic marker and therapeutic target in the treatment of estrogen dependent breast cancer patients.
    Matched MeSH terms: Phenotype
  15. Femoral-facial syndrome
    Samuel, K.F., Rasat, R.
    Malaysian Journal of Paediatrics and Child Health, 1998;10(2):59-61.
    MyJurnal
    A Malay baby boy with the femoral-facial syndrome is presented. The phenotype included bilateral femoral hypoplasia, short nose with a broad nasal tip, long philtrum with a thin upper lip, micrognathia, bilateral cryptorchidism and hypoplastic penis.
    Matched MeSH terms: Phenotype
  16. Fulltext Optimization of cell density and LPS concentration for the evaluation of nitric oxide production on BV-2 cells in a griess assay
    Nasim Karim Hosseini, Jose, Shinsmon, Vidyadaran, S., Syafinaz Amin Nordin
    Malaysian Journal of Medicine and Health Sciences, 2014;10(2):1-8.
    MyJurnal
    Introduction: Production of nitric oxide (NO) is one of the main responses elicited by a variety of
    immune cells such as macrophages (e.g. microglia, resident macrophages of brain), during inflammation. Evaluation of NO levels in the inflammatory milieu is considered important to the understanding of the intensity of an immune response; and has been performed using different methods including the Griess assay. To assay NO in culture, an appropriate number of cells are stimulated into an inflammatory phenotype. Common stimuli include lipopolysaccharide (LPS), IFN-γ and TNF-α. However, overt stimulation could cause cell cytotoxicity therefore an ideal concentration of LPS should be used. Objective: To set-up a model of BV-2 cell activation that allows the assay of detectable levels of NO. Optimization of BV-2 microglia cell density and LPS concentrations after stimulation by bacterial lipopolysaccharide (LPS) for the Griess assay is demonstrated in this study. Methods: BV-2 microglia were cultured at different cell densities, and treated with LPS at three concentrations (1, 5, 10 μg/ml). NO production in culture supernatants were then measured at 18, 24, 48 and 72 hours. Moreover, methyl tetrazolium assay (MTT) was also performed to ensure that NO measurement is performed at no-cytotoxic concentrations of LPS. Results and Conclusions: NO production follows a temporal pattern. The density of 25000 cells/ well was the ideal seeding density for NO evaluation in BV-2 cells. BV-2 stimulation by LPS is dose dependent, and NO levels are increased proportional to the LPS concentration up to 1.0μg/ml, whereas the higher LPS concentrations are associated with decreased cell viability may be caused by the high toxic levels of LPS or NO. Although Griess assay has been commonly used by the scientists, however, optimization of its parameters on BV-2 cells will be useful for the experiments which will be performed on this particular cell line. The optimized pattern of Griess assay on BV-2 cells was achieved in this study, hence easier and more practical for the future scientists to perform Griess assay on BV-2 cells.
    Matched MeSH terms: Phenotype
  17. Fulltext Iatrogenic (‘clinician-induced’) damage incurred by human sperm during infertility treatment: postgraduate research and collaborative developments between the universities of Malaya and Oxford
    Yelumalai, S., Jones, C., Coward, K.
    JUMMEC, 2013;16(2):1-6.
    MyJurnal
    Assisted Reproductive Technology (ART) is a suite of laboratory techniques designed to rescue infertile phenotypes. While ART has led to the birth of 5 million ART babies worldwide, success rates rarely exceed 40%. One potential factor for this could be iatrogenic (‘clinician-induced’) damage to critical sperm proteins, such as phospholipase C zeta (PLCζ) and protamine, which are fundamental for oocyte activation and sperm DNA integrity, respectively. This report describes how we have begun to investigate the adverse effects of ART techniques upon these key sperm proteins. We also describe the pathway taken by Miss Suseela Yelumalai to acquire a scholarship from the Malaysian Government and her postgraduate experience at the University of Oxford. We introduce the facilities and learning opportunities available at the Institute of Reproductive Sciences (IRS) which houses Dr Kevin Coward’s research laboratory, and finally, highlight the potential for collaborative development between the Universities of Oxford and Malaya.
    Matched MeSH terms: Phenotype
  18. Fulltext Prevalence of frailty syndrome and its associated factors among community-dwelling elderly in East Coast of Peninsular Malaysia
    Mohd Hamidin FA, Adznam SN, Ibrahim Z, Chan YM, Abdul Aziz NH
    SAGE Open Med, 2018;6:2050312118775581.
    PMID: 29872529 DOI: 10.1177/2050312118775581
    Objective: Frailty is a clinical syndrome with increased risk of poor health outcomes and particularly prevalent in older adults and community population. The study's aim was therefore to determine the prevalence of frailty and its association with sociodemographic and socioeconomic characteristics, health-related status, and anthropometric measurements among community-dwelling older adults.

    Methods: A total of 279 older adults aged 60 years and above were randomly selected. Respondents were classified as non-frail (<2 criteria) or frail (≥3 criteria) based on the 'phenotype of frailty'. A binary logistic regression was used to determine predictors of frailty.

    Results: The prevalence of frailty was 18.3%. The frail older adults were positively associated with advanced age, being unmarried, hospitalisation in the previous year, poor self-rated health, and lower body mass index.

    Discussion: These results give an overview on underlying effects and guiding actions for prevention programmes functioning to reverse and minimise the adverse effects of frailty syndrome.

    Matched MeSH terms: Phenotype
  19. 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: Phenotype
  20. Fulltext FGFR3 mutation increases bladder tumourigenesis by suppressing acute inflammation
    Foth M, Ismail NFB, Kung JSC, Tomlinson D, Knowles MA, Eriksson P, et al.
    J Pathol, 2018 Nov;246(3):331-343.
    PMID: 30043421 DOI: 10.1002/path.5143
    Recent studies of muscle-invasive bladder cancer show that FGFR3 mutations are generally found in a luminal papillary tumour subtype that is characterised by better survival than other molecular subtypes. To better understand the role of FGFR3 in invasive bladder cancer, we examined the process of tumour development induced by the tobacco carcinogen OH-BBN in genetically engineered models that express mutationally activated FGFR3 S249C or FGFR3 K644E in the urothelium. Both occurrence and progression of OH-BBN-driven tumours were increased in the presence of an S249C mutation compared to wild-type control mice. Interestingly, at an early tumour initiation stage, the acute inflammatory response in OH-BBN-treated bladders was suppressed in the presence of an S249C mutation. However, at later stages of tumour progression, increased inflammation was observed in S249C tumours, long after the carcinogen administration had ceased. Early-phase neutrophil depletion using an anti-Ly6G monoclonal antibody resulted in an increased neutrophil-to-lymphocyte ratio at later stages of pathogenesis, indicative of enhanced tumour pathogenesis, which supports the hypothesis that suppression of acute inflammation could play a causative role. Statistical analyses of correlation showed that while initial bladder phenotypes in morphology and inflammation were FGFR3-dependent, increased levels of inflammation were associated with tumour progression at the later stage. This study provides a novel insight into the tumour-promoting effect of FGFR3 mutations via regulation of inflammation at the pre-tumour stage in the bladder. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Phenotype
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