Abstract We present results of Short tandem repeat polymorphisms (STRPs) analysis and epidemiology study of indigenous ethnic highlanders of Daghestan and of the migrants from highlands to the lowland area in 1944, in comparison with native lowlanders. Results obtained show that demographically ancient highland ethnics have achieved a relatively stable equilibrium in their native environment and are characterized by optimal level of the main viability parameters (fertility, mortality, lifespan and morbidity). Migrants from highlands to the lowlands experienced dramatically increased morbidity and mortality in 1944–1947: up to 65–70% of total migrants had suffered malaria, typhus and other new infections and about 35–37% of total migrants had died. Genetic-epidemiological study support that non-survived migrants were characterized by a higher inbreeding rate, lower heterozygosity and higher physiological sensitivity to the environmental stress. This inter-connected complex had advantage for adaptation of the highlanders to the native environment but diminished their adaptability in the new and/or changing environment. A detailed study using STRP we performed in 1995–1999 in one highland isolate of ethnic Avars of whom about 50% were moved to the lowland area. We found significant differences in genetic and demographical structures between these highland and migrant parts of the isolate: the genetic bottleneck among migrants had a great qualitative and quantitative impact on their gene pool, i.e., lost of rare native population alleles, as well as of about 1/3 of total migrants with certain genotypes. Survived migrants demonstrate shorter lifespan and higher morbidity rate that support their still ongoing genetic adaptation to the lowland environment.