Quantitative trait loci mapping with microarray marker intensities.

ABSTRACTMany methods have been developed for mapping quantitative trait loci (QTLs) using microarrays. Traditional methods for QTL mapping rely on the assumption that biallelic genotype calls represent the complete genetic variation at a marker. In reality, the process of converting microarray intensities to discrete genotype calls results in the loss of marker information on other variations involving the marker sequence, such as nearby SNPs, deletions, or copy numbers. We have developed a novel approach to QTL mapping that directly uses microarray marker intensities. Our method scans for marker windows where the intensity distances between sample pairs are correlated with the quantitative phenotype differences. The presence of such markers indicates that samples which are genetically close together in the region also share similar phenotype values, suggesting the presence of a QTL. The significance of putative QTLs is then assessed through permutation testing. By directly incorporating genotype intensities, our method eliminates intermediate processes such as genotype calling or ancestry inference that may introduce uncertainty or data loss. We tested our method on synthetic phenotype data of mice genotyped with the 78K-marker MegaMUGA array, and our results compared favorably to those of R/qtl, a well-establishe QTL mapping package. In addition, we used our method to map the binary albino trait in inbred and backcrossed mice to the tyrosinase (Tyr) gene on chromosome 7, and we also verified several QTLs found to affect colitis-related traits from a previous mouse study.