Ethnicity-specific distribution of TRPM8 gene variants in Eurasian populations: signs of selection.

The TRPM8 gene encodes the ion channel, which is a cold receptor in afferent neurons of the mammalian somatosensory system. We studied the frequency of haplotype distribution from six SNPs in the TRPM8 gene in Eurasian human populations, including Russians, Kazakhs and Chukchi. Four of the six SNPs are located in exon 7 (rs13004520, rs28901637, rs11562975, rs17868387), rs7593557 is in exon 11. These exons encode parts of the N-terminus, which is necessary for channel functioning in the plasma membrane of neurons. The rs11563071 is in exon 23 encoding part of the C-terminus. The primary difference in population distribution of haplotypes determines the SNP from exon 11 which leads to Ser419Asn substitution in protein. The most pronounced differences in the patterns of diversity and frequencies of haplotypes were observed between Chukchi and Russians. The frequency of major H1 haplotype encompassing the 419Ser gene variant differs in examined populations; 0.738 (Russians), 0.507 (Kazakhs) and 0.337 (Chukchi), p < 0.001. The TRPM8 gene variants encoding 419Asn and carrying the minor alleles of rs28901637 (P249P) and rs11562975 (L250L) in exon 7 are characteristic of Asian populations. The frequency of all 419Asn variants in Chukchi is comparable to that in Africans, however, the minor allele frequencies of rs28901637, rs11562975 in Africans is low. Apparently in the process of human colonization of Eurasia, minor alleles of these SNPs diverged depending on rs7593557 structure in exon 11. We analyzed sequences of five TRPM8 mRNA isoforms extracted by researchers from different tissues. Sequence analysis demonstrates that they are transcribed from major H1 variant of the TRPM8 gene but contain different translation start codons, which are generated by alternative splicing from pro-mRNA.

[Respiratory system response to cooling in subjects with single nucleotide polymorphism rs11562975 in gene of thermosensitive TRPM8 ion channel].

On the basis of genomic studies in subjects belonged to Russian ethnic group it was identified individuals with heterozygous genotype, containing the C-allele in single nucleotide polymorphism rs11562975, located in 6 exon of the gene encoding the temperature-sensitive ion channel TRPM8. Subjects with heterozygous genotype GC were characterized by not only increased sensation to cold but also hypometabolic response to local skin cooling and non-temperature activation of TRPM8 ion channel by menthol--decrease in total metabolism, pulmonary ventilation and coefficient of oxygen extraction. The subjects with homozygous genotype GG had a lower cold sensation and adequate response to local skin cooling in respect to thermoregulation--decrease in respiratory heat loss and increase in the lipid metabolism.

Associations of cold receptor TRPM8 gene single nucleotide polymorphism with blood lipids and anthropometric parameters in Russian population.

We analyzed associations of single nucleotide polymorphisms rsl13004520 (R247T), rs11562975 (L250L), rs7593557 (S419N), rs11563208 (I1016I), and rs11563071 (V1058V) of the cold receptor TRPM8 (2q37.1) gene with blood plasma lipids and anthropometric parameters in Russian population (randomly chosen residents of Novosibirsk: 507 women and 459 men, mean age 57 years). The studied polymorphisms are localized in regions encoding NH2-terminal (R247T, L250L, S419N) and COOH-terminal (I1016I, V1058V) cytoplasmic domains of the channel. We showed association of single nucleotide polymorphism V1058V with the levels of total cholesterol and LDL and HDL cholesterol, and association of I1016I polymorphism with triglyceride content. Polymorphisms L250L and S419N correlated with anthropometric parameters (body mass index and waist and hip circumferences).

[Relationship of single-nucleotide polymorphism rs11562975 in thermo-sensitive ion channel TRPM8 gene with human sensitivity to cold and menthol].

The examination of people belonging to the Russian ethnic group revealed that 20.3% of subjects had heterozygous genotype, containing the C-allele in single nucleotide polymorphism rs11562975, located in exon 7 of the gene encoding the temperature-sensitive ion channel TRPM8. Functional differences, associated with sensitivity to cold and menthol were identified between subjects with different genotypes of the polymorphism rs11562975 (GG and GC). Subjects with heterozygous genotype GC were characterized by increased sensitivity to cold and reduced sensitivity to menthol, agonist of the ion channel TRPM8, compared with subjects with homozygous genotype GG.

Association of cold receptor TRPM8 gene polymorphism with blood lipid indices and anthropometric parameters in Shorians.

We analyzed single nucleotide polymorphisms of the cold receptor TRPM8 gene as genetic markers of blood serum lipid indices in Shorians. Associations were found between rs11562975 (L250L) TRPM8 gene mononucleotide polymorphism with total cholesterol and LDL cholesterol and between rs28901637 (P249P) and HDL cholesterol. No associations of P249P and L250L with triglyceride level were found. L250L polymorphism was associated with anthropometric parameters characterizing lipid metabolism (hip and waist circumferences). The TRPM8 gene is likely to be involved in the regulation of lipid metabolism.

Different patterns in molecular evolution of the Triticeae.

A huge part of the genomes of most Triticeae species is formed by different families of repetitive DNA sequences. In this paper the phylogenetic distribution of two major classes of the repeats, retrotransposons and tandemly organized DNA sequences, are considered and compared with the evolution of gene-rich regions and generally accepted Triticeae phylogenetic relationships. In Hordeum, LTR-containing retrotransposons are dispersed along the chromosomes and are consistent with the existing picture of the phylogeny of Hordeum. Another retrotransposon class, LINEs, have evolved independently from LTR-retrotransposons. Different retrotransposon classes appear to have competed for genome space during the evolution of Hordeum. Another class of repeats, tandemly organized DNA sequences, tends to cluster at the functionally important regions of chromosomes, centromeres and telomeres. The distribution of a number of tandem DNA families in Triticeae is not congruent with generally accepted phylogenetic relationships. While natural selection is the dominant factor determining the structure of genic regions we suggest that the contribution of random events is important in the evolution of repetitive DNA sequences. The interplay of stochastic processes, molecular drive, and selection determines the structure of chromosomal regions, notably at centromeres and telomeres, stabilizing and differentiating species-specific karyotypes. Thus, the evolution of these regions may occur largely independently of the evolution of gene-rich regions.

Distribution of CCR5-delta 32 gene deletion across the Russian part of Eurasia.

32-bp inactivating deletion in the beta-chemokine receptor 5 (CCR5) gene, common in Nothern European populations, is associated with reduced HIV-1 transmission risk and delayed disease progression. We have studied the deletion distribution in many populations in Eurasia by polymerase chain reaction analysis of 531 DNA samples representing West and East Siberian, Central Asian, and Far Eastern parts of Russia. An unusually high frequency (11.1%) of the deleted variant in natives of West Siberia, of Finno-Ugrian descent, was observed. Furthermore, the deletion was infrequent in indigenous populations of Central Asia, East Siberia, the Russian Far East, and Canada. We conclude that the delta(ccr5) distribution is limited primarily to Europeans and related western Siberian Finno-Ugrian populations, with a sharp negative gradient toward the east along the territory of Russian Asia.

Karyotype stabilization in intergeneric hybrids of the subtribe Triticinae : 1. The effects of genome structure.

The C-banded data obtained from Triticinae hybrids are studied with reference to the stabilization of their karyotypes. The types of hybrids distinguished according to genome structure are type I with minimally one diploid genome and type II with a haploid set only. Comparative analysis demonstrates that type I differs from II in karyotype stabilization. The chromosomes from various haploid genomes are combined into new genomes in type I; type II is represented only by amphiploids with the complete set of the chromosomes from all the genomes. The meiotic behaviour of the haploid genome chromosomes were found to have a modifying effect on karyotype stabilization: type II becomes I when homoeologous pairing level is high and when it is associated with the reductional division of univalents.