Optimization of candidate-gene SNP-genotyping by flexible oligonucleotide microarrays; analyzing variations in immune regulator genes of hay-fever samples

While the in silico process eliminated 9% of the initial probe set, which had been picked purely on the basis of potential association with disease, the subsequent experimental validation excluded more than twice as many. The performance of the optimized microarray was demonstrated in a pilot study. The genotypes of 19 hay-fever patients (aged 40–44) with high IgE levels against inhalant antigens were compared to the results obtained with 19 age- and sex-matched controls. For several variants, allele-frequency differences of more than 10% were identified.Based on the ability to improve empirically a chip design, the application of candidate-SNP typing represents a viable approach in the context of molecular epidemiological studies.Array-based technologies are revolutionizing genomics, especially the analysis of DNA variation. Array technologies are not without limitations, however, and one major drawback is the poor flexibility of typical array formats. It is cumbersome to create one's own tailored arrays by spotting DNA. Commercially available microarrays, on the other hand, either contain a fixed and usually broadly applicable content or are expensive to purchase with customized features. The fixed-content arrays are useful for taking advantage of the high resolution genetic map of the human genome that is based on single nucleotide polymorphisms [1,1], which define DNA blocks (haplotypes) [1]. Since SNPs are the most common type of genetic variation between individuals, it makes sense to utilize them for the localization of disease genes by identifying haplotypes that are associated with phenotypic traits, especially in the case of multifactorial diseases [1-5]. As a consequence of such a study, however, further analysis is required for improving the resolution of the mapping process or trying to identify the polymorphisms that are actually responsible for the phenotypic variation. Alternatively to the process described above, one can immediately focus on the ana