Genotyping, the Usefulness of Imputation to Increase SNP Density, and Imputation Methods and Tools

Abstract

Imputation has become a standard practice in modern genetic research to increase genome coverage and improve accuracy of genomic selection and genome-wide association study as a large number of samples can be genotyped at lower density (and lower cost) and, imputed up to denser marker panels or to sequence level, using information from a limited reference population. Most genotype imputation algorithms use information from relatives and population linkage disequilibrium. A number of software for imputation have been developed originally for human genetics and, more recently, for animal and plant genetics considering pedigree information and very sparse SNP arrays or genotyping-by-sequencing data. In comparison to human populations, the population structures in farmed species and their limited effective sizes allow to accurately impute high-density genotypes or sequences from very low-density SNP panels and a limited set of reference individuals. Whatever the imputation method, the imputation accuracy, measured by the correct imputation rate or the correlation between true and imputed genotypes, increased with the increasing relatedness of the individual to be imputed with its denser genotyped ancestors and as its own genotype density increased. Increasing the imputation accuracy pushes up the genomic selection accuracy whatever the genomic evaluation method. Given the marker densities, the most important factors affecting imputation accuracy are clearly the size of the reference population and the relationship between individuals in the reference and target populations.