TaqMan assays for genotyping of single nucleotide polymorphisms present at a disease susceptibility locus on chromosome 6
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Werner Koch
Abstract
Multiple single-nucleotide polymorphisms in the BAT1-NFKBIL1-LTA region on the short arm of chromosome 6 have been found to be associated with susceptibility to myocardial infarction in a recent case-control study including individuals from Japan. Specifically, the association relates to homozygosity for the minor alleles of five individual polymorphisms (one each in BAT1 and NFKBIL1 and three in LTA) and a haplotype defined by a particular allele combination of 10 polymorphisms (three each in BAT1 and NFKBIL1 and four in LTA). In the Japanese study, genotype determinations were carried out using a multiplex PCR-Invader assay or DNA sequencing. As an alternative to these methods, we have established TaqMan assays for genotyping of nine of the 10 polymorphisms. Accuracy of the genotyping results obtained with the TaqMan reactions was demonstrated in experiments involving restriction enzyme analysis or DNA sequencing. Using the new TaqMan assays, we have genotyped the polymorphisms in a group of 1211 Caucasians who presented without symptoms or signs of acute or previous myocardial infarction. Genotype distributions of each of the five myocardial infarction-associated polymorphisms were significantly different between the present study group and two Japanese control groups (p≤0.01). High linkage disequilibrium measures between polymorphisms suggested that the nine polymorphisms reside in a single haplotype block. Based on the nine polymorphisms, eight different haplotypes with allele frequencies above 1% were identified, which together represented 98.4% of the total number of chromosome 6 in the 1211 individuals. This Caucasian study group and the Japanese sample showed strong linkage disequilibrium in the myocardial infarction-associated BAT1-NFKBIL1-LTA genomic region and related haplotype content, but significantly different genotype frequencies. The new TaqMan systems provide relatively simple and fast assays to test the clinical relevance of these polymorphisms.
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©2005 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Quality control for SELDI analysis
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- Optimization and evaluation of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) with reversed-phase protein arrays for protein profiling
- Simultaneous determination of HIV antibodies, hepatitis C antibodies, and hepatitis B antigens in dried blood spots –a feasibility study using a multi-analyte immunoassay
- Hematopoietic cytokines in the sera of patients with pancreatic cancer
- Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells
- Whole genome amplification of buccal cell DNA: genotyping concordance before and after multiple displacement amplification
- Y-Chromosome short tandem repeat (STR) haplotypes in a Campania population sample
- TaqMan assays for genotyping of single nucleotide polymorphisms present at a disease susceptibility locus on chromosome 6
- The secretion of ibuprofen metabolites interferes with the capillary chromatography of urinary homovanillic acid and 4-hydroxy-3-methoxymandelic acid in neuroblastoma diagnosis
- Selective measurement of HCHO in urine using direct liquid-phase fluorimetric analysis
- A spectrophotometric micromethod for determining erythrocyte protoporphyrin-IX in whole blood or erythrocytes
- Simultaneous analysis of MDR1 C3435T, G2677T/A, and C1236T genotypes by multiplexed mutagenically separated PCR
- Measurement of reticulocyte and red blood cell indices in patients with iron deficiency anemia and β-thalassemia minor
- Chitotriosidase activity in colostrum from African and Caucasian women
- Integration between point-of-care cardiac markers in an emergency/cardiology department and the central laboratory: methodological and preliminary clinical evaluation
- Controlled storage conditions prolong stability of biochemical components in whole blood
- Poor knowledge and faulty thinking regarding hemolysis and potassium elevation
- Delayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant proteohormones in healthy male volunteers
- Evaluation of a novel semi-automated HPLC procedure for whole blood cyclosporin A confirms equivalence to adjusted monoclonal values from Abbott TDx
- Evaluation of the Bio-Rad VARIANT™ II HbA 2/HbA 1C Dual Program for measurement of hemoglobin concentrations and detection of variants
- Interferences in coagulation tests – evaluation of the 570-nm method on the Dade Behring BCS analyser
- No evidence for involvement of the human inducible nitric oxide synthase gene in susceptibility to coronary artery disease
- National survey on the use of measurement of cholinesterase activity in serum
