Genomic analysis reveals hidden heterogeneity within human population isolates

Studying groups subject to barriers to gene flow provides a unique opportunity to understand how inbreeding, genetic drift and selection have shaped the structure of human genetic diversity. Currently, the consequences of genetic isolation may be better studied using genome wide approaches (GWA), such as those based on SNP microarrays which enable the simultaneous analysis of very large numbers of loci distributed across chromosomes. Despite the considerable body of knowledge on human genetic isolates, variation occurring among individuals within isolated populations has not been yet thoroughly investigated. This issue is worth exploring since events of recent admixture and presence of sub-structure could potentially disrupt the genetic homogeneity which is expected when isolation is prolonged and constant over time. In a previous study, we have compared intra and inter- population variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Here, we expand our dataset to a total of 27 groups and move our focus to the variation among individual genomes within populations. Using four measures of within population diversity (homozygosity, identity-by-state and length and number of runs of homozygosity), we observed a significantly higher level of variation among the German-speakers of the linguistic islands of Sappada, Sauris and Timau and North Sardinians. These same populations show a noticeable among individual variation for ancestry components. Caveats, significance and implications of our results are discussed in relation to both microevolutionary aspects and bio-medical applications.