Although they are genetically distinctive in some ways, the Basques are still very typically west European in terms of their Mt-DNA and Y-DNA sequences, and in terms of many genetic loci. These same sequences are wide spread throughout the western half of Europe, especially along the western fringe of the continent. The Saami people of northern Scandinavea show an especially high abundance of an Mt-DNA type common in Basques.

It is thought that the general region of the Basque Country served as a refuge for paleolithic humans during the last major glaciation when environments further north were too cold and dry for continuous habitation. When climate warmed into the present interglacial, populations would have rapidly spread north along the west European coast. Genetically, in terms of Y-chromosomes and Mt-DNA, inhabitants of the British Isles (especially the Irish and Welsh, but also to a considerable extent the English) are closely related to the Basques [10] reflecting their common origin in this refugial area. Basques, along with Irish, show the highest frequency of the Y-chromosome DNA haplogroup R1b in Western Europe; some 90-95% of Basque men have this haplogroup. The rest is basically I and a minimal presence of E3b [11]. The genetic relationship between Basques and people of Ireland and Wales is even stronger than to neighboring areas of Southern Spain, where ethnically Spanish-speaking people now live in close proximity to the Basques. Within the R1b haplogroup are modal haplotypes. One of the best-characterized of these haplotypes is the Atlantic Modal Haplotype (AMH). In human genetics, the Atlantic Modal Haplotype (AMH) is a Y-chromosome haplotype of Y-STR microsatellite variations, associated with the R1b haplogroup. The AMH is the most frequently occurring haplotype amongst human males in Atlantic Europe.

Before the developement of modern Genetics based on DNA sequencing, Basques were noted as having the highest global apportion of Rh- blood type (35% phenetically, 60% genetically). Additionally Basques also have virtually no B blood type (nor the related AB group). These differences are though to reflect their long history of isolation, along with times when the population size of the Basques was small, allowing gene frequencies to drift over time. The history of isolation reflected in gene frequencies has presumably been key to the Basque people retaining their distinctive language, while more recently arrived Indo-European languages swamped out other indigenous languages that were previously spoken in western Europe.

I. Dupanloup et al., Estimating the Impact of Prehistoric Admixture on the Genome of Europeans

M. Pericic et al., High-Resolution Phylogenetic Analysis of Southeastern Europe Traces Major Episodes of Paternal Gene Flow Among Slavic Populations