Extremely High Carrier Frequency of the GJB2 Splice Site IVS1+1G&gt;A Mutation in Eastern Siberia is Comparable to the Carrier Frequency of the Sickle Cell Anemia in Africa

Barashkov, Nikolay A.; Solovyev, Alexey V.; Teryutin, Fedor M.; Pshennikova, Vera G.; Klarov, Leonid A.; Romanov, Georgii P.; Nakhodkin, S.S.; Savvinova, Kyunney E.; Gotovtsev, Nyurgun N.; Solovyeva, Natalya; Kozhevnikov, Andrei A.; Fedotova, Elvira E.; Pak, Maria V.; Lekhanova, S.N.; Rafailov, A. M.; Luginov, Nikolay V.; Alexeev, Anatoliy N.; Dzhemileva, Lilya U.; Khusnutdinova, Elza; Fedorova, Sardana A.; Federation, Russian; North-Eastern, Ammosov; Republic, Sakha

doi:10.23937/2378-3648/1410001

Cited by 2 publications

(4 citation statements)

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“… Note: n—number of individuals; CF—carrier frequency; CR—95% credible region. *—Data on the carrier frequency of pathogenic variants c.-23+1G>A and c.35delG in the Yakut population were compiled from previous studies [ 85 , 86 ]. …”

Section: Resultsmentioning

confidence: 99%

“… *—Data on the carrier frequency of pathogenic variants c.-23+1G>A and c.35delG in the Yakut population were compiled from previous studies [ 85 , 86 ]. …”

Section: Resultsmentioning

confidence: 99%

“…In contrast, an extremely high prevalence of the c.-23+1G>A pathogenic variant in the indigenous people living in the subarctic region of Russia (up to 13.3% in some sub-populations of the Yakuts) is comparable with the carrier frequency of the HbS allele associated with sickle cell anemia in Africa (a frequency of 10% and higher of the HbS allele was registered only in certain areas of sub-Saharan Africa) [ 86 , 90 ]. The worldwide carriers’ frequency for different GJB2 pathogenic variants is very high [ 3 , 85 ], suggesting a common selective advantage for heterozygous GJB2 variants on a global scale.…”

Section: Discussionmentioning

confidence: 99%

“…Blood samples were collected after written informed consent. The carrier frequency of the major GJB2 pathogenic variants c.-23+1G>A and c.35delG in Yakuts was calculated by a compilation of corresponding data from previous studies [ 85 , 86 ]. Differences in the c.-23+1G>A pathogenic variant frequencies between the study groups (95% credible interval) were computed with the ‘Sampling’ software kindly provided by V. Macaulay and adapted by M. Metspalu (Estonian Biocentre, Tartu, Estonia).…”

Section: Methodsmentioning

confidence: 99%

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Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic)

et al. 2016

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Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide. Until now, the spectrum and frequency of the pathogenic variants in exon 1, exon 2 and the flanking intronic regions of the GJB2 gene have not been described thoroughly in the Sakha Republic (Yakutia), which is located in a subarctic region in Russia. The complete sequencing of the non-coding and coding regions of the GJB2 gene was performed in 393 patients with HI (Yakuts—296, Russians—51, mixed and other ethnicities—46) and in 187 normal hearing individuals of Yakut (n = 107) and Russian (n = 80) populations. In the total sample (n = 580), we revealed 12 allelic variants of the GJB2 gene, 8 of which were recessive pathogenic variants. Ten genotypes with biallelic recessive pathogenic variants in the GJB2 gene (in a homozygous or a compound heterozygous state) were found in 192 out of 393 patients (48.85%). We found that the most frequent GJB2 pathogenic variant in the Yakut patients was c.-23+1G>A (51.82%) and that the second most frequent was c.109G>A (2.37%), followed by c.35delG (1.64%). Pathogenic variants с.35delG (22.34%), c.-23+1G>A (5.31%), and c.313_326del14 (2.12%) were found to be the most frequent among the Russian patients. The carrier frequencies of the c.-23+1G>A and с.109G>A pathogenic variants in the Yakut control group were 10.20% and 2.80%, respectively. The carrier frequencies of с.35delG and c.101T>C were identical (2.5%) in the Russian control group. We found that the contribution of the GJB2 gene pathogenic variants in HI in the population of the Sakha Republic (48.85%) was the highest among all of the previously studied regions of Asia. We suggest that extensive accumulation of the c.-23+1G>A pathogenic variant in the indigenous Yakut population (92.20% of all mutant chromosomes in patients) and an extremely high (10.20%) carrier frequency in the control group may indicate a possible selective advantage for the c.-23+1G>A carriers living in subarctic climate.

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Section: Resultsmentioning

confidence: 99%

“… *—Data on the carrier frequency of pathogenic variants c.-23+1G>A and c.35delG in the Yakut population were compiled from previous studies [ 85 , 86 ]. …”

Section: Resultsmentioning

confidence: 99%