2010/06/22

The Long History of the European People

    A large proportion of diseases that affect the welfare of human populations have a genetic component. Researchers have put in a vast effort in order to correlate the incidence of a particular disease with a particular gene. Those efforts have been unsuccessful in many cases, particularly with diseases considered multi-causal, where there could be a strong environmental component or where several genes could be implicated. Under this scenario, genetically isolated populations are extremely valuable for epidemiological studies, as the cause-effect relationship is best discriminated when the genetic variability among individuals is low. For this reason, worldwide, a lot of effort is made to characterize genetically distinct human populations, in order to understand how genes contribute to disease and, very importantly, how variations in those genes affect the individual responses to medication and environmental conditions. For instance, the Human Genome Diversity Project provides DNA of 1050 different individuals from 51 different populations, including Africa, Americas, Asia, Europe and Oceania. Another well known example is the Icelandic Cancer Project, where a significant proportion of the people became voluntarily involved in one of the largest population genotyping projects.

   The Basque population shows some epidemiological peculiarities, showing high prevalence of certain diseases, such as the limb-girdle muscular dystrophy, certain type of Parkinsonism and others. The question that arises here is whether the Basque population could be considered an isolated group, which could be useful in disease association studies. Previous work done by many groups, using technology available in the past decades, indicated that this was indeed the case, as the Basques exhibit certain polymorphisms in a different proportion than other European populations, including their French and Spanish neighbors. The studies directed by Dr. A. M. Aransay from CIC bioGUNE, in a collaborative effort with the University of the Basque Country and the Basque Foundation for Health Innovation and Research, using state-of-the-art, high-throughput technology, confirm the peculiarity of the Basque populations settled on both sides of the Pyrenees. In a recent publication, Rodríguez-Ezpeleta and co-workers present the analysis of more than 60,000 single nucleotide polymorphisms in 83 individuals from the provinces of Alava, Biscay, Guipuscoa and Navarre. They compare this group with the French Basques and other European populations, and show that all Basques constitute a homogeneous group that can be differentiated from other European populations.

   Besides the use of new powerful technology, the strength of the study resides in the strict criteria followed in the process of sample classification and collection. Family history of the donors was confirmed, using parish and civil registries data, to certify that the family lived in the same province for at least four generations. Donors were hematologically and physically examined and they were certified unrelated to each other for at least three generations. All the samples are publicly available through the Basque Biobank for Research. The thorough process of sample selection, as well as some other methodological aspects, might be at the core of the discrepancies with other high-throughput results published recently.

   The genome wide analysis of the Basque population is, therefore, an important tool for the association of certain genes with certain diseases. In addition, from an epidemiological point of view, it is important to determine how the polymorphisms shown in other European populations are conserved among the Basques, which will determine the applicability of a particular treatment. From a different point of view, the high-throughput analysis of the genome will help us to understand the part of our past that is only written in our genes: how the prehistoric human migratory movements gave rise to the today's Europeans. This type of study, as performed by Rodríguez-Ezpeleta and co-workers, among others, will contribute to deciphering of the fascinating history of present human populations.