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Polymorphism Genotyping (polymorphism + genotyping)

Distribution by Scientific Domains
Medical Sciences55%
Life Sciences33%

Kinds of Polymorphism Genotyping

  • nucleotide polymorphism genotyping
    		•
  • single nucleotide polymorphism genotyping
    		•

    Selected Abstracts

    Determination of ABCB1 polymorphisms and haplotypes frequencies in a French population

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007
    Elise Jeannesson
    Abstract The ATP-binding cassette (ABC) transporter ABCB1, or P-glycoprotein, is a transmembrane efflux pump well known for its implication in drug transport and chemoresistance. ABCB1 substrates include either drugs, such as antiretrovirals and immunomodulators, or physiological molecules like phospholipids. Pharmacogenetic analysis of ABCB1 polymorphisms, in addition to other xenobiotic metabolizing enzymes, might help to personalize and optimize drug therapy. Indeed, some polymorphisms of ABCB1 have been implicated in susceptibility to diseases, changes in drug pharmacokinetics, and in variation of the biological response to drug treatment. In addition, variant and haplotype distributions differ depending on ethnicity. Thus, some ethnies may be at higher risk for adverse events, inefficacy of treatment or prevalence of pathologies. This study aimed to determine frequencies of ABCB1 polymorphisms and haplotypes in a sample of French healthy individuals. DNA was isolated from blood-EDTA. Polymerase chain reaction-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism genotyping assays were used to genotype 227 individuals for T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms. The observed frequencies of the variant allele for these eight polymorphisms are 0.04, 0.08, 0.09, 0.06, 0.42, 0.46, 0.45 and 0.46 respectively. These polymorphisms are in linkage disequilibrium and haplotype frequencies were determined, the most frequent haplotype being the one with variants at position 1236, 2677 and 3435 and wild-type alleles at the other positions. Finally, the frequencies of these eight ABCB1 polymorphisms in our French individuals supposed to be healthy population are quite similar to those described in other Caucasian populations except for the C3435T polymorphism. [source]

    Calculation of IBD probabilities with dense SNP or sequence data

    GENETIC EPIDEMIOLOGY, Issue 6 2008
    Jonathan M. Keith
    Abstract The probabilities that two individuals share 0, 1, or 2 alleles identical by descent (IBD) at a given genotyped marker locus are quantities of fundamental importance for disease gene and quantitative trait mapping and in family-based tests of association. Until recently, genotyped markers were sufficiently sparse that founder haplotypes could be modelled as having been drawn from a population in linkage equilibrium for the purpose of estimating IBD probabilities. However, with the advent of high-throughput single nucleotide polymorphism genotyping assays, this is no longer a reasonable assumption. Indeed, the imminent arrival of individual sequencing will enable high-density single nucleotide polymorphism genotyping on a scale for which current algorithms are not equipped. In this paper, we present a simple new model in which founder haplotypes are modelled as a Markov chain. Another important innovation is that genotyping errors are explicitly incorporated into the model. We compare results obtained using the new model to those obtained using the popular genetic linkage analysis package Merlin, with and without using the cluster model of linkage disequilibrium that is incorporated into that program. We find that the new model results in accuracy approaching that of Merlin with haplotype blocks, but achieves this with orders of magnitude faster run times. Moreover, the new algorithm scales linearly with number of markers, irrespective of density, whereas Merlin scales supralinearly. We also confirm a previous finding that ignoring linkage disequilibrium in founder haplotypes can cause errors in the calculation of IBD probabilities. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source]

    The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-, and ribavirin combined therapy for chronic hepatitis C patients

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2008
    P.-J. Chen
    Summary Interferon-, and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-, and ribavirin combined therapy in patients with chronic hepatitis C. [source]

    Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan

    JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2008
    Ching-Yu Yen
    Background:, Many single nucleotide polymorphisms (SNPs) have been found to be associated with oral cancer but the biological interactions through SNPs are seldom addressed. In this study, we focused on the joint effect for SNP combinations of four DNA repair genes, X-ray repair cross-complementing groups (XRCCs) 1,4, involved in major cancer-related pathways. Methods:, Single nucleotide polymorphism genotyping was determined using by polymerase chain reaction-restriction fragment length polymorphism in this study (case = 103, control = 98). Different numbers of combinational SNPs with genotypes called the pseudo-haplotypes from these chromosome-wide genes were used to evaluate their joint effect on oral cancer risk. Results:, Except for XRCC2 rs2040639-AG, none of these SNPs was found to individually contribute to oral cancer risk. However, for two combined SNPs, the proportion of subjects with oral cancer was significantly higher in the pseudo-haplotype with AG-CC genotypes in rs2040639-rs861539 (XRCC2,XRCC3) compared with those with non-AG-CC genotypes. Similarly, the pseudo-haplotype of rs2040639,rs861539,rs2075685 (XRCC2,XRCC3,XRCC4) and rs2040639,rs861539,rs2075685,rs1799782 (XRCCs 1,4) with specific genotype pattern (AG-CC-TG and CT-AG-CC-TG) among three and four combinational SNPs were significantly associated with oral cancer. After controlling for age, gender, smoking, drinking, and betel nut chewing, the estimated odds ratio of oral cancer were 2.45, 5.03, and 10.10 for two, three and four specific SNP combinations, respectively, comparing these specific pseudo-haplotypes to their corresponding non-pseudo-haplotypes. Conclusion:, We have identified the potential combined XRCCs 1,4 SNPs with genotypes that were associated with oral cancer risk and may have an impact on identification of a high-risk population. [source]

    Combined effect of IL-10 and TGF-,1 promoter polymorphisms as a risk factor for aspirin-intolerant asthma and rhinosinusitis

    ALLERGY, Issue 8 2009
    S.-H. Kim
    Background:, It has been known that interleukin (IL)-10 promoter polymorphisms at ,1082A/G, ,819T/C and ,592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-,. The goal of this study was to investigate a gene,gene interaction between IL-10 and TGF-,1 polymorphisms in Korean asthmatics with aspirin hypersensitivity. Methods:, Single-nucleotide polymorphism genotyping of IL-10 and TGF-,1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay. Results:, Among the patients with asthma, polymorphism at ,1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF-,1,509C/T and IL-10,1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-,1,509C/T and AG or GG genotype of IL-10,1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504,11.235). In an in vitro functional assay, the ,1082G reporter plasmid exhibited significantly greater promoter activity when compared with the ,1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the ,1082G allele. Conclusion:, Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-,1. [source]

    Characterization of single nucleotide polymorphism markers for the green sea turtle (Chelonia mydas)

    MOLECULAR ECOLOGY RESOURCES, Issue 3 2009
    SUZANNE E. RODEN
    Abstract We present data on 29 new single nucleotide polymorphism assays for the green sea turtle, Chelonia mydas. DNA extracts from 39 green turtles were used for two methods of single nucleotide polymorphism discovery. The first approach employed an amplified fragment length polymorphism technique. The second technique screened a microsatellite library. Allele-specific amplification assays were developed for high-throughput single nucleotide polymorphism genotyping and tested on two Pacific C. mydas nesting populations. Observed heterozygosities ranged from 0 to 0.95 for a Hawaiian population and from 0 to 0.85 for a Galapagos population. Each of the populations had one locus out of Hardy,Weinberg equilibrium, SSCM2b and SSCM5 for Hawaii and Galapagos, respectively. No loci showed significant genotypic linkage disequilibrium across an expanded set of four Pacific nesting populations. However, two loci, SSCM4 and SSCM10b showed linkage disequilibrium across three populations indicating possible association. [source]

    Single nucleotide polymorphism genotyping of the barley waxy gene by polymerase chain reaction with confronting two-pair primers

    PLANT BREEDING, Issue 3 2004
    E. Domon
    Abstract A high-throughput single nucleotide polymorphism (SNP) genotyping procedure was developed to select amylose-free barley mutants whose waxy genes had a C- to T-base substitution in exon 5, which converted Gln-89 of the wild-type gene into a termination codon. An F2 population carrying an amylose-free waxy gene was checked for segregation. Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) produced allele-specific PCR products that have different sizes and are inherited in a co-dominant manner. Two alleles of the barley waxy gene with SNP were correctly identified in parental strains using the PCR-CTPP procedure. Segregation of the SNP as detected by PCR-CTPP in an F2 population fitted the expected 1:2:1 ratio. The PCR-CTPP procedure can provide a time saving and cost-effective alternative to derived cleaved amplified polymorphic sequence in marker-assisted selection. [source]

    A Single Molecular Beacon Probe Is Sufficient for the Analysis of Multiple Nucleic Acid Sequences

    CHEMBIOCHEM, Issue 12 2010
    Yulia V. Gerasimova Dr.
    Abstract Molecular beacon (MB) probes are dual-labeled hairpin-shaped oligodeoxyribonucleotides that are extensively used for real-time detection of specific RNA/DNA analytes. In the MB probe, the loop fragment is complementary to the analyte: therefore, a unique probe is required for the analysis of each new analyte sequence. The conjugation of an oligonucleotide with two dyes and subsequent purification procedures add to the cost of MB probes, thus reducing their application in multiplex formats. Here we demonstrate how one MB probe can be used for the analysis of an arbitrary nucleic acid. The approach takes advantage of two oligonucleotide adaptor strands, each of which contains a fragment complementary to the analyte and a fragment complementary to an MB probe. The presence of the analyte leads to association of MB probe and the two DNA strands in quadripartite complex. The MB probe fluorescently reports the formation of this complex. In this design, the MB does not bind the analyte directly; therefore, the MB sequence is independent of the analyte. In this study one universal MB probe was used to genotype three human polymorphic sites. This approach promises to reduce the cost of multiplex real-time assays and improve the accuracy of single-nucleotide polymorphism genotyping. [source]

    Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease in German children

    ACTA PAEDIATRICA, Issue 11 2009
    Martin Lacher
    Abstract Aim:, Genome-wide association studies have described an association of the ATG16L1 (autophagy 16-like 1) gene rs2241880 variant with Crohn's disease (CD). Therefore, we evaluated this polymorphism in early-onset CD in 152 children and 253 controls and for the first time determined ATG16L1 colonic expression in German CD children. Methods:, Investigation of rs2241880 allele frequencies using a predesigned single nucleotide polymorphism genotyping assay. Analysis of digenic epistasis between rs2241880 and the three common nucleotide-binding oligomerization domain containing two (NOD2/CARD15) mutations. Determination of ATG16L1 gene expression in large-bowel biopsies of selected patients and controls using real-time polymerase chain reaction. Results:, The rs2241880G risk allele frequency was higher in CD compared with controls (63.0% vs. 47.4%; p = 0.0002). No epistasis between NOD2/CARD15 mutations and rs2241880 was observed; however, carriers of both variants had significantly increased disease risk. Transcriptional analysis did not reveal over- or underexpression of ATG16L1 in CD patients compared with controls. Conclusion:, We confirmed the association of CD with ATG16L1 rs2241880 variant in early-onset CD. As no epistatic interaction with three common NOD2/CARD15 mutations was observed, the p.Thr300Ala substitution is an independent risk factor for paediatric CD and supports the role for autophagy in disease pathogenesis. [source]