Recent resequencing of the whole genome or the coding part of the genome (the exome) in thousands of individuals has described a large excess of low frequency variants in humans, probably arising as a consequence of recent rapid growth in human population sizes. Most rare variants are private to specific populations and are enriched for functional mutations, thus potentially having some medical relevance. In a recent study, scientists analyze whole-exome sequences from over a hundred individuals from the French-Canadian population, which was founded less than 400 years ago by about 8,500 French settlers who colonized the province between the 17th and 18th centuries. They showed that in a remarkably short period of time this population has accumulated substantial differences, including an excess of rare, functional and potentially damaging variants, when compared to the original European population. These results show the effects of population history on genetic variation that may have an impact on genetic fitness and disease, and have implications in the design of genetic studies, highlighting the importance of extending deep resequencing to worldwide human populations.