Using DNA pools for genotyping trios

The genotyping of mother-father-child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies mayreducepower,sinceitrequiresthegenotypingof three individuals where only four independent hap- lotypes are involved. We describe here a method for genotypingatriousingtwoDNApools,thusreducing the cost of genotyping trios to that of genotyping two individuals. Furthermore, we present extensions to the method that exploit the linkage disequilibrium structure to compensate for missing data and geno- typing errors. We evaluated our method on trios from CEPH pedigree 66 of the Coriell Institute. We demon- strate that the error rates in the genotype calls of the proposed protocol are comparable to those of stan- dard genotyping techniques, although the cost is reduced considerably. The approach described is generic and it can be applied to any genotyping platform that achieves a reasonable precision of allele frequency estimates from pools of two indi- viduals. Using this approach, future trio-based asso- ciation studies may be able to increase the sample size by 50% for the same cost and thereby increase the power to detect associations.