Structuring the Genetic Heterogeneity of the Basque Population: A View from Classical Polymorphisms

In this study we analyze 18 classical polymorphisms (ABO, Rh, MNSs, Lewis, P, Duffy, Kell, ADA, ESD, PGM1, PGD, AK1, ACP1, GLO1, HP, GC, TF, and PI) in over 2000 autochthonous individuals from 14 natural districts in three provinces of the Basque Country (Alava, Guipuzcoa, and Biscay). Heterogeneity analysis via the χ 2 test and a calculation of FST in- dicate that there is significant genetic heterogeneity between the Basque dis- tricts. The R matrix informs us that this heterogeneity is not significantly con- centrated in a single district or in the districts of a single province, but is rather distributed among several districts belonging to the three provinces an- alyzed. We undertake to assess the influence of various historical, geographi- cal, and cultural factors on the genetic structure of the Basque population. Analysis suggests that allele distribution is geographically patterned in the Basque Country. The gradient distributions observed in the case of some al- leles (ABO*O, RH*cDE, RH*cde, MNS*MS, and ACP1*C) on the basis of Moran's autocorrelation coefficient I, along with the influence of the two main travel routes through the Basque Country (western route through Bil- bao and eastern route through Vitoria), suggest that the gene flow tends to- ward the coast. As regards other factors considered (administrative division, repopulation processes, linguistic heterogeneity, and north vs. south cultural heterogeneity), we detected only a certain influence exerted by an old tribal differentiation (2000 b.p.), which would diminish with the passage of time. The Basque population is of great interest in the field of population genetics be- cause of its singular genetic characteristics, which clearly distinguish it from oth- er Western European populations. The Basques live at the western end of the Pyrenees in a region divided administratively into three small provinces in France (Labourd, Basse-Navarre, and Soule) and two "Autonomous Communities" in Spain (the Basque Autonomous Community or BAC, which comprises the provinces of Biscay, Alava, and Guipuzcoa, and the Chartered Community of Navarre; see Figure 1). Because most of the genetic studies carried out to date