Displaying publications 1 - 20 of 631 in total

Abstract:
Sort:
  1. Fulltext Brain-Derived Neurotrophic Factor Polymorphism and Aphasia after Stroke
    Lee NT, Ahmedy F, Mohamad Hashim N, Yin KN, Chin KL
    Behav Neurol, 2021;2021:8887012.
    PMID: 34367374 DOI: 10.1155/2021/8887012
    Stroke is one of the most deliberating causes of mortality and disability worldwide. Studies have implicated Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene as a genetic factor influencing stroke recovery. Still, the role of BDNF polymorphism in poststroke aphasia is relatively unclear. This review assesses the recent evidence on the association between the BDNF polymorphism and aphasia recovery in poststroke patients. The article highlights BNDF polymorphism characteristics, speech and language interventions delivered, and the influence of BNDF polymorphism on poststroke aphasia recovery. We conducted a literature search through PubMed and Google Scholar with the following terms: "brain derived-neurotrophic factor" and "aphasia" for original articles from January 2000 until June 2020. Out of 69 search results, a detailed selection process produced a total of 3 articles that met the eligibility criteria. All three studies included Val66Met polymorphism as the studied human BDNF gene. One of the studies demonstrated insufficient evidence to conclude that BDNF polymorphism plays a role in poststroke aphasia recovery. The remaining two studies have shown that Met allele genotype (either single or double nucleotides) was associated with poor aphasia recovery, in either acute or chronic stroke. Carriers of the Val66Met polymorphism of BDNF gave a poorer response to aphasia intervention and presented with more severe aphasia.
    Matched MeSH terms: Polymorphism, Single Nucleotide
  2. Fulltext Evaluating the possibility of detecting evidence of positive selection across Asia with sparse genotype data from the HUGO Pan-Asian SNP Consortium
    Liu X, Saw WY, Ali M, Ong RT, Teo YY
    BMC Genomics, 2014;15:332.
    PMID: 24885517 DOI: 10.1186/1471-2164-15-332
    The HUGO Pan-Asian SNP Consortium (PASNP) has generated a genetic resource of almost 55,000 autosomal single nucleotide polymorphisms (SNPs) across more than 1,800 individuals from 73 urban and indigenous populations in Asia. This has offered valuable insights into the correlation between the genetic ancestry of these populations with major linguistic systems and geography. Here, we attempt to understand whether adaptation to local climate, diet and environment partly explains the genetic variation present in these populations by investigating the genomic signatures of positive selection.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  3. Maximum likelihood parentage assignment using quantitative genotypes
    Hamilton MG
    Heredity (Edinb), 2021 06;126(6):884-895.
    PMID: 33692533 DOI: 10.1038/s41437-021-00421-0
    The cost of parentage assignment precludes its application in many selective breeding programmes and molecular ecology studies, and/or limits the circumstances or number of individuals to which it is applied. Pooling samples from more than one individual, and using appropriate genetic markers and algorithms to determine parental contributions to pools, is one means of reducing the cost of parentage assignment. This paper describes and validates a novel maximum likelihood (ML) parentage-assignment method, that can be used to accurately assign parentage to pooled samples of multiple individuals-previously published ML methods are applicable to samples of single individuals only-using low-density single nucleotide polymorphism (SNP) 'quantitative' (also referred to as 'continuous') genotype data. It is demonstrated with simulated data that, when applied to pools, this 'quantitative maximum likelihood' method assigns parentage with greater accuracy than established maximum likelihood parentage-assignment approaches, which rely on accurate discrete genotype calls; exclusion methods; and estimating parental contributions to pools by solving the weighted least squares problem. Quantitative maximum likelihood can be applied to pools generated using either a 'pooling-for-individual-parentage-assignment' approach, whereby each individual in a pool is tagged or traceable and from a known and mutually exclusive set of possible parents; or a 'pooling-by-phenotype' approach, whereby individuals of the same, or similar, phenotype/s are pooled. Although computationally intensive when applied to large pools, quantitative maximum likelihood has the potential to substantially reduce the cost of parentage assignment, even if applied to pools comprised of few individuals.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  4. Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations
    Cha PC, Yamada R, Sekine A, Nakamura Y, Koh CL
    J Hum Genet, 2004;49(10):558-572.
    PMID: 15372322 DOI: 10.1007/s10038-004-0190-z
    The extensive nucleotide diversity in drug-related genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  5. The details are in the genome-wide SNPs: Fine scale evolution of the Malaysian weedy rice
    Sudo MPS, Yesudasan R, Neik TX, Masilamany D, Jayaraj J, Teo SS, et al.
    Plant Sci, 2021 Sep;310:110985.
    PMID: 34315600 DOI: 10.1016/j.plantsci.2021.110985
    Weedy rice (Oryza spp.) is a major nuisance to rice farmers from all over the world. Although the emergence of weedy rice in East Malaysia on the island of Borneo is very recent, the threat to rice yield has reached an alarming stage. Using 47,027 genotyping-by-sequencing (GBS)-derived SNPs and candidate gene analysis of the plant architecture domestication gene TAC1, we assessed the genetic variations and evolutionary origin of weedy rice in East Malaysia. Our findings revealed two major evolutionary paths for genetically distinct weedy rice types. Whilst the cultivar-like weedy rice are very likely to be the weedy descendant of local coexisting cultivars, the wild-like weedy rice appeared to have arisen through two possible routes: (i) accidental introduction from Peninsular Malaysia weedy rice populations, and (ii) weedy descendants of coexisting cultivars. The outcome of our genetic analyses supports the notion that Sabah cultivars and Peninsular Malaysia weedy rice are the potential progenitors of Sabah weedy rice. Similar TAC1 haplotypes were shared between Malaysian cultivated and weedy rice populations, which further supported the findings of our GBS-SNP analyses. These different strains of weedy rice have convergently evolved shared traits, such as seeds shattering and open tillers. A comparison with our previous simple-sequence repeat-based population genetic analyses highlights the strength of genome-wide SNPs, including detection of admixtures and low-level introgression events. These findings could inform better strategic management for controlling the spread of weedy rice in the region.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  6. Understanding the genetic relationships between Indonesian bambara groundnut landraces and investigating their origins
    Redjeki ES, Ho WK, Shah N, Molosiwa OO, Ardiarini NR, Kuswanto, et al.
    Genome, 2020 Jun;63(6):319-327.
    PMID: 32097026 DOI: 10.1139/gen-2019-0137
    A total of 170 bambara groundnut (Vigna subterranea) accessions were evaluated using both simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers generated using genotyping-by-sequencing (GbS), of which 56 accessions were collected from West and East Java. Principal coordinate analysis (PCoA), population structure, and cluster analysis suggest that the East Java accessions could be a result of the introduction of selected West Java accessions. In addition, the current Indonesian accessions were likely introduced from Southern Africa, which would have produced a very marked founding effect such that these accessions present only a fraction of the genetic variability that exists within this species.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  7. Bayesian multivariant fine mapping using the Laplace prior
    Walters K, Yaacob H
    Genet Epidemiol, 2023 Apr;47(3):249-260.
    PMID: 36739616 DOI: 10.1002/gepi.22517
    Currently, the only effect size prior that is routinely implemented in a Bayesian fine-mapping multi-single-nucleotide polymorphism (SNP) analysis is the Gaussian prior. Here, we show how the Laplace prior can be deployed in Bayesian multi-SNP fine mapping studies. We compare the ranking performance of the posterior inclusion probability (PIP) using a Laplace prior with the ranking performance of the corresponding Gaussian prior and FINEMAP. Our results indicate that, for the simulation scenarios we consider here, the Laplace prior can lead to higher PIPs than either the Gaussian prior or FINEMAP, particularly for moderately sized fine-mapping studies. The Laplace prior also appears to have better worst-case scenario properties. We reanalyse the iCOGS case-control data from the CASP8 region on Chromosome 2. Even though this study has a total sample size of nearly 90,000 individuals, there are still some differences in the top few ranked SNPs if the Laplace prior is used rather than the Gaussian prior. R code to implement the Laplace (and Gaussian) prior is available at https://github.com/Kevin-walters/lapmapr.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  8. Aluminum Microcomb Electrodes on Silicon Wafer for Detecting Val66Met Polymorphism in Brain-Derived Neurotrophic Factor
    Li Z, Cui L, Zhao H, Du J, Gopinath SCB, Lakshmipriya T, et al.
    Dev Neurosci, 2021;43(1):53-62.
    PMID: 33849012 DOI: 10.1159/000515197
    OBJECTIVE: Brain-derived neurotrophic factor (BDNF) dysregulation is widely related with various psychiatric and neurological disorders, including schizophrenia, depression, Rett syndrome, and addiction, and the available evidence suggests that BDNF is also highly correlated with Parkinson's and Alzheimer's diseases.

    METHODS: The BDNF target sequence was detected on a capture probe attached on aluminum microcomb electrodes on the silicon wafer surface. A capture-target-reporter sandwich-type assay was performed to enhance the detection of the BDNF target.

    RESULTS: The limit of detection was noticed to be 100 aM. Input of a reporter sequence at concentrations >10 aM improved the detection of the target sequence by enhancing changes in the generated currents. Control experiments with noncomplementary and single- and triple-mismatches of target and reporter sequences did not elicit changes in current levels, indicating the selective detection of the BDNF gene sequence.

    CONCLUSION: The above detection strategy will be useful for the detection and quantification of BDNF, thereby aiding in the provision of suitable treatments for BDNF-related disorders.

    Matched MeSH terms: Polymorphism, Single Nucleotide
  9. Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations
    Teh LK, Subramaniam V, Tuan Abdu Aziz TA, Lee LS, Ismail MI, Yu CY, et al.
    Drug Metab. Pharmacokinet., 2016 Aug;31(4):304-13.
    PMID: 27325019 DOI: 10.1016/j.dmpk.2016.04.004
    We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  10. Fulltext Association between the C34T polymorphism of the AMPD1 gene and essential hypertension in Malaysian patients
    Nemati R, Lu J, Ramachandran V, Etemad A, Heidari M, Yahya MJ, et al.
    Genet. Mol. Res., 2016 Jun 20;15(2).
    PMID: 27323204 DOI: 10.4238/gmr.15026241
    The aim of this study was to determine whether C34T, a common polymorphism of the adenosine monophosphate deaminase 1 gene (AMPD1), is associated with essential hypertension (EH). We hypothesize that C34T is associated with the development of EH. A case-control design was used for this study. The DNA was extracted using a commercial kit from the whole blood of 200 patients with hypertension and 200 subjects without hypertension from selected Malaysian ethnicities (Malays, Chinese, and Indians). Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used for genotyping. The C34T gene polymorphism of AMPD1 was significantly associated with EH in the Malaysian subjects (P < 0.0001). The genotype frequencies of CC, CT, and TT were 6%, 79%, and 15%, respectively, among hypertensive subjects, while no TT genotypes were observed in the normotensive subjects. Further, the frequency of hypertension was higher among T allele carriers than C carriers (OD = 9.94; 95%CI = 6.851-14.434). There were significant differences in the systolic blood pressure, diastolic blood pressure, and pulse pressure (P ˂ 0.05) between the normotensive and hypertensive Malaysian subjects; we believe those difference were caused by the C34T polymorphism. For the first time in Malaysia, the current study provides evidence that a common polymorphism of the AMPD1 gene (C34T) is strongly associated with EH.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  11. Fulltext Design and characterization of a 52K SNP chip for goats
    Tosser-Klopp G, Bardou P, Bouchez O, Cabau C, Crooijmans R, Dong Y, et al.
    PLoS One, 2014;9(1):e86227.
    PMID: 24465974 DOI: 10.1371/journal.pone.0086227
    The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  12. Association between inflammatory bowel disease gene 5 (IBD5) and interleukin-23 receptor (IL23R) genetic polymorphisms in Malaysian patients with Crohn's disease
    Chua KH, Hilmi I, Lian LH, Patmanathan SN, Hoe SZ, Lee WS, et al.
    J Dig Dis, 2012 Sep;13(9):459-65.
    PMID: 22908971 DOI: 10.1111/j.1751-2980.2012.00617.x
    This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  13. A novel single nucleotide polymorphism, IVS2 -97A>T, in the prostaglandin F2alpha receptor gene was identified among the Malaysian patients with glaucoma
    Peng HB, Zahary MN, Tajudin LS, Lin CL, Teck CM, Sidek MR, et al.
    Kobe J Med Sci, 2007;53(1-2):49-52.
    PMID: 17582204
    The Prostaglandin F2alpha (PGF2alpha) receptor gene has been found to play an important role in reducing the intraocular pressure of the glaucomatous patients. Variations of the PGF2alpha receptor gene may be responsible for the differences in the response to an antiglaucoma drug, Latanoprost. A combined method of denaturing High Performance Liquid Chromatography (dHPLC) and sequencing was applied to detection of the PGF2alpha receptor gene variant among the 76 Malaysian patients with glaucoma, and a novel single nucleotide polymorphism (SNP), IVS -97A>T, was identified. According to the genotyping analysis, 36.8% of the subjects were heterozygous for the variant allele T, while 9.2% homozygous. The frequency of variant allele T was 0.28. Although with a limited number of samples, our data suggested that this polymorphism is common in the Malaysian patients with glaucoma.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  14. Letter regarding "CD95 rs1800682 polymorphism and cervical cancer risk: evidence from a meta-analysis" by Zhang et al
    Tan SC
    Tumour Biol., 2015 Nov;36(11):8275-6.
    PMID: 26515334 DOI: 10.1007/s13277-015-4330-1
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  15. Fulltext Genome-wide association study of prostate cancer-specific survival
    Szulkin R, Karlsson R, Whitington T, Aly M, Gronberg H, Eeles RA, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Nov;24(11):1796-800.
    PMID: 26307654 DOI: 10.1158/1055-9965.EPI-15-0543
    BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.

    METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).

    RESULTS: We observed no significant association between genetic variants and prostate cancer survival.

    CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study.

    IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics
  16. Fulltext Fine-scale population structure and ecotypes of anadromous Hilsa shad (Tenualosa ilisha) across complex aquatic ecosystems revealed by NextRAD genotyping
    Asaduzzaman M, Wahab MA, Rahman MJ, Nahiduzzzaman M, Dickson MW, Igarashi Y, et al.
    Sci Rep, 2019 11 05;9(1):16050.
    PMID: 31690767 DOI: 10.1038/s41598-019-52465-2
    The anadromous Hilsa shad (Tenualosa ilisha) live in the Bay of Bengal and migrate to the estuaries and freshwater rivers for spawning and nursing of the juveniles. This has led to two pertinent questions: (i) do all Hilsa shad that migrate from marine to freshwater rivers come from the same population? and (ii) is there any relationship between adults and juveniles of a particular habitat? To address these questions, NextRAD sequencing was applied to genotype 31,276 single nucleotide polymorphism (SNP) loci for 180 individuals collected from six strategic locations of riverine, estuarine and marine habitats. FST OutFLANK approach identified 14,815 SNP loci as putatively neutral and 79 SNP loci as putatively adaptive. We observed that divergent local adaptations in differing environmental habitats have divided Hilsa shad into three genetically structured ecotypes: turbid freshwater (Western Riverine), clear freshwater (Eastern Riverine) and brackish-saline (Southern Estuarine-Marine). Our results also revealed that genes involved in neuronal activity may have facilitated the juveniles' Hilsa shad in returning to their respective natal rivers for spawning. This study emphasized the application of fundamental population genomics information in strategizing conservation and management of anadromous fish such as Hilsa shad that intersect diverse ecotypes during their life-history stages.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  17. Fulltext Sexual reproduction and genetic polymorphism within the cosmopolitan marine diatom Pseudo-nitzschia pungens
    Kim JH, Ajani P, Murray SA, Kim JH, Lim HC, Teng ST, et al.
    Sci Rep, 2020 06 30;10(1):10653.
    PMID: 32606343 DOI: 10.1038/s41598-020-67547-9
    Different clades belonging to the cosmopolitan marine diatom Pseudo-nitzschia pungens appear to be present in different oceanic environments, however, a 'hybrid zone', where populations of different clades interbreed, has also been reported. Many studies have investigated the sexual reproduction of P. pungens, focused on morphology and life cycle, rather than the role of sexual reproduction in mixing the genomes of their parents. We carried out crossing experiments to determine the sexual compatibility/incompatibility between different clades of P. pungens, and examined the genetic polymorphism in the ITS2 region. Sexual reproduction did not occur only between clades II and III under any of experimental temperature conditions. Four offspring strains were established between clade I and III successfully. Strains established from offspring were found interbreed with other offspring strains as well as viable with their parental strains. We confirmed the hybrid sequence patterns between clades I and III and found novel sequence types including polymorphic single nucleotide polymorphisms (SNPs) in the offspring strains. Our results implicate that gene exchange and mixing between different clades are still possible, and that sexual reproduction is a significant ecological strategy to maintain the genetic diversity within this diatom species.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  18. Fulltext Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations
    Arciero E, Kraaijenbrink T, Asan, Haber M, Mezzavilla M, Ayub Q, et al.
    Mol Biol Evol, 2018 08 01;35(8):1916-1933.
    PMID: 29796643 DOI: 10.1093/molbev/msy094
    We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 and Egl-9 Family Hypoxia Inducible Factor 1 loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments.
    Matched MeSH terms: Polymorphism, Single Nucleotide*
  19. In silico analysis of nonsynonymous single nucleotide polymorphisms of the human adiponectin receptor 2 (ADIPOR2) gene
    Solayman M, Saleh MA, Paul S, Khalil MI, Gan SH
    Comput Biol Chem, 2017 Jun;68:175-185.
    PMID: 28359874 DOI: 10.1016/j.compbiolchem.2017.03.005
    Polymorphisms of the ADIPOR2 gene are frequently linked to a higher risk of developing diseases including obesity, type 2 diabetes and cardiovascular diseases. Though mutations of the ADIPOR2 gene are detrimental, there is a lack of comprehensive in silico analyses of the functional and structural impacts at the protein level. Considering the involvement of ADIPOR2 in glucose uptake and fatty acid oxidation, an in silico functional analysis was conducted to explore the possible association between genetic mutations and phenotypic variations. A genomic analysis of 82 nonsynonymous SNPs in ADIPOR2 was initiated using SIFT followed by the SNAP2, nsSNPAnalyzer, PolyPhen-2, SNPs&GO, FATHMM and PROVEAN servers. A total of 10 mutations (R126W, L160Q, L195P, F201S, L235R, L235P, L256R, Y328H, E334K and Q349H) were predicted to have deleterious effects on the ADIPOR2 protein and were therefore selected for further analysis. Theoretical models of the variants were generated by comparative modeling via MODELLER 9.16. A protein structural analysis of these amino acid variants was performed using SNPeffect, I-Mutant, ConSurf, Swiss-PDB Viewer and NetSurfP to explore their solvent accessibility, molecular dynamics and energy minimization calculations. In addition, FTSite was used to predict the ligand binding sites, while NetGlycate, NetPhos2.0, UbPerd and SUMOplot were used to predict post-translational modification sites. All of the variants showed increased free energy, though F201S exhibited the highest energy increase. The root mean square deviation values of the modeled mutants strongly indicated likely pathogenicity. Remarkably, three binding sites were detected on ADIPOR2, and two mutations at positions 328 and 201 were found in the first and second binding pockets, respectively. Interestingly, no mutations were found at the post-translational modification sites. These genetic variants can provide a better understanding of the wide range of disease susceptibility associated with ADIPOR2 and aid the development of new molecular diagnostic markers for these diseases. The findings may also facilitate the development of novel therapeutic elements for associated diseases.
    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics*
  20. Fulltext The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications
    Say YH
    J Physiol Anthropol, 2017 Jun 14;36(1):25.
    PMID: 28615046 DOI: 10.1186/s40101-017-0142-x
    BACKGROUND: Despite the fact that insertions/deletions (INDELs) are the second most common type of genetic variations and variable number tandem repeats (VNTRs) represent a large portion of the human genome, they have received far less attention than single nucleotide polymorphisms (SNPs) and larger forms of structural variation like copy number variations (CNVs), especially in genome-wide association studies (GWAS) of complex diseases like polygenic obesity. This is exemplified by the vast amount of review papers on the role of SNPs and CNVs in obesity, its related traits (like anthropometric measurements, biochemical variables, and eating behavior), and its related complications (like hypertension, hypertriglyceridemia, hypercholesterolemia, and insulin resistance-collectively known as metabolic syndrome). Hence, this paper reviews the types of INDELs and VNTRs that have been studied for association with obesity and its related traits and complications. These INDELs and VNTRs could be found in the obesity loci or genes from the earliest GWAS and candidate gene association studies, like FTO, genes in the leptin-proopiomelanocortin pathway, and UCP2/3. Given the important role of the brain serotonergic and dopaminergic reward system in obesity susceptibility, the association of INDELs and VNTRs in these neurotransmitters' metabolism and transport genes with obesity is also reviewed. Next, the role of INS VNTR in obesity and its related traits is questionable, since recent large-scale studies failed to replicate the earlier positive associations. As obesity results in chronic low-grade inflammation of the adipose tissue, the proinflammatory cytokine gene IL1RA and anti-inflammatory cytokine gene IL4 have VNTRs that are implicated in obesity. A systemic proinflammatory state in combination with activation of the renin-angiotensin system and decreased nitric oxide bioavailability as found in obesity leads to endothelial dysfunction. This explains why VNTR and INDEL in eNOS and ACE, respectively, could be predisposing factors of obesity. Finally, two novel genes, DOCK5 and PER3, which are involved in the regulation of the Akt/MAPK pathway and circadian rhythm, respectively, have VNTRs and INDEL that might be associated with obesity.

    SHORT CONCLUSION: In conclusion, INDELs and VNTRs could have important functional consequences in the pathophysiology of obesity, and research on them should be continued to facilitate obesity prediction, prevention, and treatment.

    Matched MeSH terms: Polymorphism, Single Nucleotide/genetics
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links