Soutenance de thèse Joanna GIEMZA

Fine-scale genetic structure in human populations is interesting for two main reasons: 1), it reflects historical and demographic events, 2) it informs research on disease association studies. This thesis aims to perform a thorough analysis of the genetic structure of the population from continental France, in particular Northwestern France, and shed light on the historical, demographic and cultural events that have shaped it, by taking advantage of three genome-wide datasets (SU.VI.MAX/3C and PREGO) At the country level we report the correlation between genetic data and birthplaces of individuals in two independent French cohorts (1,414 and 770 individuals in SU.VI.MAX and 3C, respectively) and identify six clusters, concordant between datasets,
and may correspond to ancient political, cultural and geographical borders. The second study takes advantage of the PREGO cohort including 3,234 individuals with three generations of ancestry linked to specific regions of Northwestern France and reveals fine-scale structure at an unprecedented level (154 subpopulations). The resulting genetic clusters and the characterisation of their effective population size and ancestry proportions compared to other European groups provide important and novel insights into the
historical peopling of France and potential explanations for different disease prevalence within
this northwestern region. Overall, my thesis work indicate substantial levels of
population stratification within a geographically limited region likely caused by different demographic histories across the region.