High-throughput microarray-based genotyping

A high throughput genotyping platform that scores over 10,000 single-nucleotide polymorphisms (SNPs) per individual on a single GeneChip® high-density oligonucleotide microarray has been developed to conduct studies to elucidate the genetic basis for complex diseases. Currently, the genotyping of individual SNPs relies on the summary statistics (based on the observed intensities of probes on the microarray) for the entirety of the sample set. A classification scheme of those statistics across hundreds of individual DNA samples is obtained to make individual genotyping calls. In contrast to the current approach, the method in this work makes individual genotyping call by finding the minimum residual, i.e. highest likelihood, among four possible states corresponding to three genotypes and no-call. Initially, the residual is calculated based on a given set of probe affinities for that individual sample. Auspiciously, the multitude of samples was utilized to iterate to refine the probe affinities, sample concentration, and background intensities. These refined parameters entail an improved call rate while maintaining high accuracy.