The analysis of the nucleotide sequences of exons and adjacent non-coding regions of the GC gene in 108 representatives of various ethnic groups of aboriginal population of Siberia was carried out. Polymorphism was found in four nucleotide positions: non-synonymous substitutions at the rs4588 and rs7041 loci, a synonymous substitution at the rs4752 locus, and a replacement in the non-coding region at the rs3733359 locus. Seven haplotypes of the GC gene were identified. Of these, 4 haplotypes encode the Gc1F isoform, 2 haplotypes encode the Gc1S isoform, and 1 haplotype encodes the Gc2 isoform. Between-regional differences were found in the distribution of variants of the GC gene: in the northeast and in the central part of Siberia, the highest prevalence of the Gc1F and Gc1F / Gc1F variants is observed, and in the south and west of Siberia, the Gc2, Gc1S / Gc2 and Gc2 / Gc2 variants are most common. In the case of the GC gene, gene-environment interactions are apparently aimed at creating a balance between the activity of vitamin D-binding protein and the level of 25-hydroxyvitamin D in the blood serum.

A review of features of polymorphism of lipid and carbohydrate metabolism genes in aboriginal populations of Siberia is presented. The most significant genetic changes in aboriginal populations of Northeast Asia (Eskimos, Chukchi and Koryaks) are described, related to long-term adaptation to extreme conditions of the natural environment and dietary characteristics. Part of the genetic variability of aboriginal populations of this region is represented by polymorphisms associated with metabolic disorders (deficiency of carnitine palmitoyltransferase 1A, pancreatic amylase, sucrase-isomaltase, trehalase) caused by the change of the traditional protein-lipid diet to “European” carbohydrate one. In modern conditions, it is extremely important to perform large-scale genetic testing of aboriginal populations of the Far North.

Background. Exome polymorphism is a rich source of information on the structure and function of proteins and metabolic pathways. The traditional diet of native populations of Northeast Asia (Eskimos, Chukchi and Koryaks) is enriched with fatty acids, which presupposes the existence of adaptive rearrangements of the lipid metabolism system among northern aborigines. Carnitine acyltransferases are the most important group of enzymes that metabolize fatty acids. Materials and methods. To study adaptive changes in the genes encoding for the carnitine acyltransferases, we performed a screening of polymorphisms in the exons of CPT1A, CPT1B, CPT1C, CPT2, CRAT, and CROT genes in various populations of native inhabitants of Siberia. Results. In exons of five genes (with the exception of CROT), 16 non-synonymous substitutions were identified. Of these, three substitutions were detected at high frequencies in populations of Northeast Asia (in Eskimos, Chukchi and Koryaks): at the loci rs80356779 of the CPT1A gene (replacement of P479L) and rs763273578 of the CPT1C gene (T740A), as well as a new polymorphism at position 131866581 of chromosome 9 at the CRAT gene (S99F). Exome analysis showed that among native populations of Northeast Asia, new non-synonymous substitutions with high pathogenicity indices appeared in the genes of energy metabolism and lipid exchange (genes GK2, ABHD6, NCOA2, OSPL3, LRP10, TTN, and PTTG2). Conclusion. It is assumed that new variants of non-synonymous polymorphism arose as a result of genetic adaptation of native peoples to the extremely cold climate and a specific “Arctic” diet of aborigines of the Far North.

Background. In polymorphism rs1815739, a C → T transition converts arginine to a premature stop-codon at residue 577 of the alpha-actinin-3 (ACTN3) protein (R577X polymorphism). This polymorphism may affect muscle performance, and the derived 577X allele has been found to be under-represented in sprint/power athletes. In addition, loss of alpha-actinin-3 results in a shift in muscle metabolism toward the more efficient aerobic pathway, thus pointing that this polymorphism may have been involved in enhancing the capability for hunting and for cold adaptation. Here, we study rs1815739 polymorphism in native populations (Chukchi, Koryaks and Evens) and newcomers (Russians) of North-Eastern Asia. Materials and methods. Genomic DNA was isolated from peripheral blood. ACTN3 genotypes for rs1815739 locus were established by enzymatic digestion of amplicons with DdeI. Heterozygotes TT were confirmed by DNA sequencing. In addition, data on exome variation in Siberian populations were analyzed. Results. Lowered frequencies (less than 40%) of “mutant” allele rs1815739-T were found in studied populations of North-Eastern Asia. Analysis of exome data has shown that haplotype comprising the rs1815739-T allele reaches the highest frequencies in populations of Southern and Central Siberia, while it is rather rare in the north-east of Siberia. Conclusion. The results obtained contradict the hypothesis that the rs1815739 polymorphism may have been involved in cold adaptation of North-East Siberians.