ALMAZY YAKUTIA RUSSIA UPDATE

Specific c.35delG prevalence and discovery of common STR- and SNP-haplotypes bearing the c.35delG mutation in Mediterranean, Middle Eastern, North-European populations, and in individuals of European origin in the USA support this hypothesis. According to a generally accepted hypothesis, c.35delG originated from a common ancestor in the Middle East or the Mediterranean approximately 10,000–14,000 years ago and spread throughout Europe with Neolithic migrations. Nevertheless, convincing evidence emerged that the founder effect plays an important role in the prevalence and accumulation of c.35delG in populations of Caucasian origin since lower rates or absence of c.35delG are observed in other populations. The occurrence of c.35delG as a possible “hot spot” caused by DNA polymerase “slippage” was previously assumed to be an explanation of the high prevalence of this pathogenic variant in the GJB2 gene. The c.35delG is a deletion of one guanine (G) from a string of six (GGGGGG) in the GJB2 coding sequence resulting in a frameshift and termination of the Cx26 protein sequence at amino acid 13 (p.Gly12Valfs*2). In meta-analysis of the data published up to 2008, mean carrier frequencies of c.35delG were found to be 1.89, 1.52, 0.64, 1, and 0.64% for European, American, Asian, Oceanic, and African populations, respectively. Previous studies have revealed the c.35delG carrier frequency to be around 1 in 50 overall in Europe, reaching 1 in 31 in Southern Europe. The recessive pathogenic GJB2 variant c.35delG (p.Gly12Valfs*2) (NM_004004.5) is known to be prevalent in deaf patients of Caucasian origin. Many of them have high ethno-geographic specificity in prevalence, which for certain ethnic groups is being attributed to a founder effect. Over 300 pathogenic variations in GJB2 have been reported in the Human Gene Mutation Database. Pathogenic variants in the GJB2 gene (MIM 121011, chromosome 13q11q12) are the most common causes of autosomal recessive non-syndromic hearing loss in various populations.

A rough estimation of the c.35delG age in Siberia (about 4800 to 8100 years ago) probably reflects the early formation stages of the modern European population (including the European part of the contemporary territory of Russia) since the settlement of Siberia by Russians started only at the end of sixteenth century. Comparative analysis of the c.35delG haplotypes supports a common origin of c.35delG in some regions of Russia (Volga-Ural region and Siberia) and in Eastern Europe (Belarus). Conclusionsĭistribution of the c.35delG carrier frequency in Russia is characterized by pronounced ethno-geographic specificity with a downward trend from west to east. Moreover, identical allelic composition of the two most frequent c.35delG haplotypes restricted by D13S141 and D13S175 was established in geographically remote regions: Siberia and Volga-Ural region (Russia) and Belarus (Eastern Europe). We present updated carrier rates for c.35delG in Russia complemented by new data on c.35delG carrier frequency in Russians living in Western Siberia (4.1%). For reconstruction of haplotypes bearing c.35delG, polymorphic D13S141, D13S175, D13S1853 flanking the GJB2 gene, and intragenic rs3751385 were genotyped in deaf patients homozygous for c.35delG ( n = 24) and in unrelated healthy individuals negative for c.35delG ( n = 67) living in Siberia. The carrier frequency of c.35delG was estimated in 122 unrelated hearing individuals living in Western Siberia. To test the c.35delG common origin hypothesis, we have reconstructed haplotypes bearing c.35delG and evaluated the approximate age of c.35delG in Siberia. According to a generally accepted hypothesis, c.35delG originated from a common ancestor in the Middle East or the Mediterranean ~ 10,000–14,000 years ago and spread throughout Europe with Neolithic migrations.

ALMAZY YAKUTIA RUSSIA UPDATE

We aimed to estimate the carrier frequency of c.35delG in Western Siberia and thereby update current data on the c.35delG prevalence in Russia. Data on the c.35delG prevalence in Russia are mainly restricted to the European part of this country. The well-known mutation c.35delG is more frequent in populations of Caucasian origin. Mutations in GJB2 gene are a major causes of deafness and their spectrum and prevalence are specific for various populations.

Almazy yakutia russia