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Kalmyks, the only Mongolic-speaking population in Europe, live in the southeast of the European Plain, in Russia. They adhere to Buddhism and speak a dialect of the Mongolian language. Historical and linguistic evidence, as well a shared clan names, suggests a common origin with Oirats of western Mongolia; yet, only a limited number of genetic studies have focused on this topic. Here we compare the paternal genetic relationship of Kalmyk clans with ethnographically related groups from Mongolia, Kyrgyzstan and China, within the context of their neighbouring populations. A phylogeny of 37 high-coverage Y-chromosome sequences, together with further genotyping of larger sample sets, reveals that all the Oirat-speaking populations studied here, including Kalmyks, share, as a dominant paternal lineage, Y-chromosomal haplogroup C3c1-M77, which is also present in several geographically distant native Siberian populations. We identify a subset of this clade, C3c1b-F6379, specifically enriched in Kalmyks as well as in Oirat-speaking clans in Inner Asia. This sub-clade coalesces at around 1500 years before present, before the Genghis Khan era, and significantly earlier than the split between Kalmyks and other Oirat speakers about 400 years ago. We also show that split between the dominant hg C variant among Buryats—C3-M407—and that of C3-F6379, took place in the Early Upper Palaeolithic, suggesting an extremely long duration for the dissipation of hg C3-M217 carriers across northern Eurasia, which cuts through today’s major linguistic phyla.

Cystic fibrosis (CF) is a common monogenic disease caused by pathogenic variants in the CFTR gene. The distribution and frequency of CFTR variants vary in different countries and ethnic groups. The spectrum of pathogenic variants of the CFTR gene was previously studied in more than 1,500 CF patients from different regions of the European and North Caucasian region of Russia and the spectrum of the most frequent pathogenic variants of the CFTR gene and ethnic features of their distribution were determined. To assess the population frequency of CFTR gene mutations some of the common variants were analyzed in the samples of healthy unrelated individuals from the populations of the European part of the Russian Federation: 1,324 Russians from four European regions (Pskov, Tver, Rostov, and Kirov regions), representatives of five indigenous ethnic groups of the Volga-Ural region [Mari (n = 505), Udmurts (n = 613), Chuvash (n = 780), Tatars (n = 704), Bashkirs (n = 517)], and six ethnic groups of the North Caucasus [Karachay (n = 324), Nogais (n = 118), Circassians (n = 102), Abazins (n = 128), Ossetians (n = 310), and Chechens (n = 100)]. The frequency of common CFTR mutations was established in studied ethnic groups. The frequency of F508del mutation in Russians was found to be 0.0056 on average, varying between four regions, from 0.0027 in the Pskov region to 0.0069 in the Rostov region. Three variants W1282X, 1677delTA, and F508del were identified in the samples from the North Caucasian populations: in Karachay, the frequency of W1282X mutation was 0.0092, 1677delTA mutation – 0.0032; W1282X mutation in the Nogais sample – 0.0127, the frequency of F508del mutations was 0.0098 and 1677delTA – 0.0098 in Circassians; in Abazins F508del (0.0039), W1282X (0.0039) and 1677delTA (0.0117) mutations were found. In the indigenous peoples of the Volga-Ural region, the maximum frequency of the F508del mutation was detected in the Tatar population (0.099), while this mutation was never detected in the Mari and Bashkir populations. The E92K variant was found in Chuvash and Tatar populations. Thus, interethnic differences in the spectra of CFTR gene variants were shown both in CF patients and in healthy population of the European and North Caucasian part of Russia.

Hereditary nonsyndromic sensorineural hearing loss is a disease in which hearing loss occurs due to damage to the organ of the inner ear, the auditory nerve, or the center in the brain that is responsible for the perception of sound, characterized by wide locus and allelic heterogeneity and different types of inheritance. Given the diversity of population of the Russian Federation, it seems necessary to study the ethnic characteristics of the molecular causes of the disease. The aim is to study the molecular and genetic causes of hereditary sensorineural hearing loss in Chuvash, the fifth largest ethnic group in Russia. DNA samples of 26 patients from 21 unrelated Chuvash families from the Republic of Chuvashia, in whom the diagnosis of hereditary sensorineural hearing loss had been established, were analyzed using a combination of targeted Sanger sequencing, multiplex ligase-dependent probe amplification, and whole exome sequencing. The homozygous variant NM_133261.3(GIPC3):c.245A>G (p.Asn82Ser) is the major molecular cause of hereditary sensorineural hearing loss in 23% of Chuvash patients (OMIM #601869). Its frequency was 25% in patients and 1.1% in healthy Chuvash population. Genotyping of the NM_133261.3(GIPC3):c.245A>G (p.Asn82Ser) variant in five neighboring populations from the Volga-Ural region (Russian, Udmurt, Mary, Tatar, Bushkir) found no evidence that this variant is common in those populations.

Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun.AimTo evaluate frequencies and genetic background of complex alleles carrying c.1521_1523delCTT (F508del) and c.1399C>T (L467F), c.2562T>G (T854=) or c.4389G>A (Q1463=) in cis; to determine clinical consequences of complex allele c.[1399C>T;1521_1523delCTT] ([L467;F508del]) in Russian CF patients.MethodsSequencing of coding regions of CFTR gene and analysis of polymorphic markers in CF patients carrying F508del variant. Comparing of clinical features in two groups patients having genotypes [L467F;F508del];[F508del] (group 1) and [F508del];[F508del] (group 2).ResultsFrequency of [L467F;F508del] allele linked to 2–2–21–6–17–13 haplotype was 4.42%, of [F508del;T854=;Q1463=] allele linked to haplotype 1–2–21–6–17–13 – 2.2% in F508del chromosomes. No differences in disease severity in patients carrying complex allele [L467F;F508del] and patients homozygous for F508del was found.ConclusionThe frequency of complex alleles associated with F508del was at least 6.6% in Russian CF patients, which should be taken into account for the decision on optimal treatment options with CFTR modulators.

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We analyzed the data on the variability of the Y chromosome and mitochondrial DNA (mtDNA) in populations of the Tsaatans of Mongolia and the Tozhu Tuvans of Russia. The populations studied are characterized by low genetic diver¬sity for both marker systems. The analysis of Y chromosome haplogroups in the Tsaatan and Tozhu revealed three hap¬logroups in the Tsaatan and seven haplogroups in the Tozhu. The composition of the haplogroups is coherent to literature data on the Tuvans, which is explained by common origin. According to the data on mitochondrial DNA variability, 12 haplogroups were determined in 46 Tozhus, of which C4b (30.43%) and F1b1b (23.91%) are major haplogroups. According to the HVS–1 (HyperVariable Segment) data, 15 haplotypes were found in the Tozhu Tuvans and the diversity coefficient of 0.8677 turned out to be much lower than among the Torghut of Mongolia (0.9857). In 23 Tsaatans, 14 haplogroups were determined; the most common of which are C4b (22.73%) and C5a1 (18.18%). According to HVS-1, 14 haplotypes were revealed in the Tsaatan, the diversity is 0.9486. The data obtained on uniparental marker systems in the Tozhus and Tsaatans are due to the isolated and inaccessible taiga region and the manifestation of the “founder effect”. The Tsaatans are less polymorphic in terms of the variety of Y chromosome haplogroups, while the Tozhus are less polymorphic in terms of mitochondrial DNA, which is probably a consequence of a high rate of endogamic marriages in the populations studied.

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