We propose the "most diverse reference panel", defined as the subset with the maximal "phylogenetic diversity", thereby incorporating individuals that span a diverse range of genotypes within the sample.
We propose the use of the most diverse reference panel for genotype imputation, adapting the greedy algorithm for maximizing phylogenetic diversity in our selection of an internal reference panel.
Our results indicate the following sequencing study design guidelines which take advantage of the recent advances in genotype imputation methodology: Select the largest and most diverse reference panel for sequencing and genotype as many "anchor" markers as possible.
Based on results from this study, we recommend a few guidelines in designing sequencing studies to take advantage of the recent advances in genotype imputation methodology: Select the largest and most diverse reference panel for sequencing, with respect to both haplotypes and phenotype.
For all sequence lengths considered, the most diverse reference panels provide lower discordance rates than the randomly selected reference panels.
We analyze simulated data sets to evaluate the performance of the "most diverse reference panel" in genotype imputation.
Based on the genotyped markers, we select the most diverse reference panel to impute the genotypes of the masked sites.
The lower discordance rates from the most diverse reference panels are observed across all frequency bins for heterozygote sites.
Sites imputed with the most diverse reference panels have a mean r ^ 2 of 0.749 across sites.
We select the most diverse reference panel using our method and 50 reference panels randomly without replacement.
A program to select the most diverse reference panel using the greedy algorithm is available in C++ upon request.
