RESUMO
We have developed a robust microarray genotyping chip that will help advance studies in genetic epidemiology. In population-based genetic association studies of complex disease, there could be hidden genetic substructure in the study populations, resulting in false-positive associations. Such population stratification may confound efforts to identify true associations between genotype/haplotype and phenotype. Methods relying on genotyping additional null single nucleotide polymorphism (SNP) markers have been proposed, such as genomic control (GC) and structured association (SA), to correct association tests for population stratification. If there is an association of a disease with null SNPs, this suggests that there is a population subset with different genetic background plus different disease susceptibility. Genotyping over 100 null SNPs in the large numbers of patient and control DNA samples that are required in genetic association studies can be prohibitively expensive. We have therefore developed and tested a resequencing chip based on arrayed primer extension (APEX) from over 2000 DNA probe features that facilitate multiple interrogations of each SNP, providing a powerful, accurate, and economical means to simultaneously determine the genotypes at 110 null SNP loci in any individual. Based on 1141 known genotypes from other research groups, our GC SNP chip has an accuracy of 98.5%, including non-calls.
Assuntos
Análise Mutacional de DNA/instrumentação , Testes Genéticos/métodos , Genética Populacional/instrumentação , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Polimorfismo de Nucleotídeo Único/genética , Animais , Análise Mutacional de DNA/métodos , Sondas de DNA , Desenho de Equipamento , Análise de Falha de Equipamento , Perfilação da Expressão Gênica/instrumentação , Perfilação da Expressão Gênica/métodos , Variação Genética , Genética Populacional/métodos , Genótipo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
UNLABELLED: SNP Chart is a Java application for the visualization and interpretation of microarray genotyping data primarily derived from arrayed primer extension-based chemistries. Spot intensity output files from microarray analysis tools are imported into SNP Chart, together with a multi-channel TIFF image of the original array experiment and a list of the actual single nucleotide polymorphisms (SNPs) being tested. Data from different and/or replicate probes that interrogate the same SNP, but that are scattered across the array grid, can be reassembled into a single chart format, specific for the SNP. This allows a quick and very effective 'visualization'/'quality control' of the data from multiple probes for the same SNP that can be easily interpreted and manually scored as a genotype. AVAILABILITY: http://www.snpchart.ca.