Research Article: Haplotype Diversity and Reconstruction of Ancestral Haplotype Associated with the c.35delG Mutation in the GJB2 (Cx26) Gene among the Volgo-Ural Populations of Russia

Date Published: , 2011

Publisher: A.I. Gordeyev

Author(s): L.U. Dzhemileva, O.L. Posukh, N.A. Barashkov, S.A. Fedorova, F.M. Teryutin, 
V.L. Akhmetova, I.M. Khidiyatova, R.I. Khusainova, S.L. Lobov, E.K. Khusnutdinova.



The mutations in theGJB2(Сх26) gene make the
biggest contribution to hereditary hearing loss. The spectrum and prevalence of
theGJB2gene mutations are specific to populations of
different ethnic origins. For severalGJB2 mutations, their
origin from appropriate ancestral founder chromosome was shown, approximate
estimations of “age” obtained, and presumable regions of
their origin outlined. This work presents the results of the carrier
frequencies’ analysis of the major (for European countries) mutation
c.35delG (GJB2gene) among 2,308 healthy individuals from 18
Eurasian populations of different ethnic origins: Bashkirs, Tatars, Chuvashs,
Udmurts, Komi-Permyaks, Mordvins, and Russians (the Volga-Ural region of
Russia); Byelorussians, Ukrainians (Eastern Europe); Abkhazians, Avars,
Cherkessians, and Ingushes (Caucasus); Kazakhs, Uzbeks, Uighurs (Central Asia);
and Yakuts, and Altaians (Siberia). The prevalence of the c.35delG mutation in
the studied ethnic groups may act as additional evidence for a prospective role
of the founder effect in the origin and distribution of this mutation in various
populations worldwide. The haplotype analysis of chromosomes with the c.35delG
mutation in patients with nonsyndromic sensorineural hearing loss (N=112) and in
population samples (N =358) permitted the reconstruction of an ancestral
haplotype with this mutation, established the common origin of the majority of
the studied mutant chromosomes, and provided the estimated time of the c.35delG
mutation carriers expansion (11,800 years) on the territory of the Volga-Ural

Partial Text

Hereditary deafness is a frequent disorder in humans: it is recorded in 1/1,000
newborns. The etiology and pathogenesis of this disease are still to be clarified;
however, approximately half of the cases of hereditary deafness are a result of
genetic disorders [1].

The material taken for the haplotypic analysis and estimates of the
“age” of c.35delG of the gene GJB2 was 56 DNA
samples (112 chromosomes) obtained from patients with NSHL, residing in the
Volga-Ural regions, in which the mutation.35delG was identified in the homozygote
state (32 Russians, 10 Tatars, 1 Bashkirs, 4 Ukrainians, 2 Armenians, and 7
individuals of mixed ethnicity). The control group included 179 (358 chromosomes)
healthy individuals from three ethno-geographical groups of the Russians (
N = 86); Tatars ( N = 62); and Bashkirs (
N = 31) without this mutation.

In many populations worldwide, the main contributor to the development of
nonsyndromic sensorineural hearing loss (NSHL) is the mutations of the
GJB2 gene. In most European populations, up to 40–50%
of cases of NSHL are preconditionally caused by one of the major recessive mutations
of this gene, c.35delG, which is revealed in the homozygous or compound-heterozygous
state [41]. In connection with this, many
researchers have analyzed the carrier frequency of c.35delG in a variety of
populations in the world. A large-scale study which embraced 17 European countries
showed that the mean carrier frequency of the c.35delG mutation amounts to 1.96%
(1/51), ranging from 2.86% (1/35) in South-European countries to 1.26% (1/79) in
Northern Europe [42]. In the Mediterranean
region, the highest carrier frequency of c.35delG were observed in Greece (3.5%), in
the southern regions of Italy (4.0%), and in France (3.4%) [43]. As a result of the meta-analysis of the c.35delG carrier
frequency in over 23,000 individuals from different populations, carried out on the
basis of the data published between the years of 1998 and 2008, the average regional
frequencies of c.35delG were determined in the European (1.89%), American (1.52%),
Asian (0.64%), and African (0.64%) populations, as well as in Oceania (1%). Also,
the decreasing gradient of the carrier frequency of c.35delG (from 2.48 to 1.53%)
from south to north in European populations and from west to east (from 1.48 to
0.1%) in Asian populations [44] was

The analysis of the carrier frequency of the mutation c.35delG in the
GJB2 genein Eurasian populations has revealed a tendency
towards gradient decrease in the c.35delG frequency from West to East, starting from
the populations of Eastern Europe and the Volga-Ural region, with average
frequencies of 3.3 and 1.4%, respectively; a low frequency (0.8–0.9%) in
Central Asian populations, a minimum frequency (0.4%) in Yakuts residing in Eastern
Siberia; and the absence of с.35delG in Altaians (Southern