When using an external reference panel as a template for imputation, the most important challenge for successfully imputing genotypes in genome scan samples is ensuring that alleles are labeled consistently (that is, on the same strand) in the reference sample being used and in the samples where missing genotypes will be imputed. MACH checks that allele frequencies are similar in the reference panel and in the samples being imputed, but it cannot catch all errors. In practice, we have found it extremely useful to genotype a small number of HapMap samples as part of each genomewide scan – this helps evaluate genotyping error rates but also ensures that consistency of allele labels can be easily checked.
