Straightforward Inference of Ancestry and AdmixtureProportions through Ancestry-Informative Insertion Deletion Multiplexing

Abstract

Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographicallydistant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual orestimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of greatinterest in clinical genetics research, particularly to detect and correct for population substructure effects in case-controlassociation studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informativeinsertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins(African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs)through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency ofthe assay in clustering populations from different continental origins and to establish reference databases. In addition, otherpopulations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The resultsrevealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides goodestimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly availableAIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotypingtechnologies.