Herzig, A. F. | Search bioRxiv

bioRxiv2022

Can imputation in a European country be improved by local reference panels? The example of France

France has a population with extensive internal fine-structure; and while public imputation reference panels contain an abundance of European genomes, there include few French genomes. Intuitively, using a study specific panel (SSP) for France would therefore likely be beneficial. To investigate, we imputed 550 French individuals using either the University of Michigan imputation server with the Haplotype Reference Consortium panel, or in-house using an SSP of 850 whole-genome sequenced French individuals. With approximate geo-localization of both our target and SSP individuals we are able to pinpoint different scenarios where SSP-based imputation would be preferred over server-based imputation or vice-versa. We could also show to a high degree of resolution how the proximity of the reference panel to a target individual determined the accuracy of both haplotype phasing and genotype imputation. Previous comparisons of different strategies have shown the benefits of combining public reference panels with SSPs. Getting the best out of both resources simultaneously is unfortunately impractical. We put forward a pragmatic solution where server-based and SSP-based imputation outcomes can be combined based on comparing posterior genotype probabilities. Such an approach can give a level of imputation accuracy markedly in excess of what could be achieved with either strategy alone.

genetics↗

bioRxiv2022

Genetic population structure across Brittany and the downstream Loire basin provides new insights on the demographic history of Western Europe

European genetic ancestry originates from three main ancestral populations - Western hunter-gatherers, early European farmers and Yamnaya Eurasian herders - whose edges geographically met in present-day France. Despite its central role to our understanding of how the ancestral populations interacted and gave rise to modern population structure, the population history of France has remained largely understudied. Here, we analysed the high-coverage whole-genome sequences and genome-wide genotype profiles of respectively 856 and 3,234 present-day individuals from the northern half of France, and merged them with publicly available present-day and ancient Europe-wide genotype datasets. We also explored, for the first time, the whole-genome sequences of six mediaeval individuals (300-1100 CE) from Western France to gain insights into the genetic impact of what is commonly known as the Migration Period in Europe. We found extensive fine-scale population structure across Brittany and the downstream Loire basin, emphasising the need for investigating local populations to better understand the distribution of rare and putatively deleterious variants across space. Overall, we observed an increased population differentiation between the northern and southern sides of the river Loire, which are characterised by different proportions of steppe vs. Neolithic-related ancestry. Samples from Western Brittany carry the largest levels of steppe ancestry and show high levels of allele sharing with individuals associated with the Bell Beaker complex, levels that are only comparable with those found in populations lying on the northwestern edges of Europe. Together, our results imply that present-day individuals from Western Brittany retain substantial legacy of the genetic changes that occurred in Northwestern Europe following the arrival of the Bell Beaker people c. 2500 BCE. Such genetic legacy may explain the sharing of disease-related alleles with other present-day populations from Western Britain and Ireland.

genetics↗