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From a historic and genetic point of view, the Otomi of the Mezquital Valley are a frontier people that have played an important role in the making of the population dynamics of the Mexican Central Plateau. Due to their antiquity in the area, the Otomi may be bearers of ancient genetic variability, shared mainly today with other groups belonging to the Otomanguean linguistic family and with the Nahua.

This study analyzes the HLA class II allele frequencies reported in Mexican indigenous populations, in order to provide an intra-regional level historical perspective of the genetic relationships between the Otomi of the Mezquital Valley and indigenous populations from other regions of Mexico. We examined genetic variation in HLADRB1 and -DQB1 loci in 66 non-related individuals belonging to seven indigenous communities from the Ixmiquilpan municipality in the Mezquital Valley, in the State of Hidalgo, Mexico.

The variability of the HLA-DRB1 gene among the Otomi of the Mezquital Valley is mainly concentrated in five alleles: -DRB1*08:02 (31.06%), -DRB1*04:07 (25.77%), -DRB1*14:06 (7.55%), -DRB1*14:02 (6.06%) and -DRB1*16:02 (4.55%), these alleles have been previously described in other indigenous populations. The most frequent alleles at the HLA-DQB1 locus are -DQB1*03:02 (34.09%), -DQB1*04:02 (31.03%) and -DQB1*03:01 (19.7%). Furthermore, HLA-DQB1*02:02 allele is found in the Otomi group with a frequency of 2.27%, notably this allele has not been reported in Mexican indigenous populations.

In conclusion, the genetic constitution of the Otomi population is intermediate to the northern groups and the genetic variability shared by the peoples of the central regions of Mexico. Furthermore, HLA-DRB1 and -DQB1 allelic variability among the Otomi, provides an insight into the historical processes implied in the biological 4 admixture with European, Asian and African populations as well as in the admixture with the population of Mexico City associated to long-standing migratory processes.