Assessment of variability in the genetic load of orphan hereditary diseases in the populations of the Republic of North Ossetia – Alania

Background. Data on the genetic load of orphan hereditary diseases (OHDs) in human populations are few, variable across populations and ethnic groups, and on average account for 0.5-2% of the population. The results of a comprehensive genetic epidemiologic study of the population of the Republic of North Ossetia  Alania (RNOA) are presented.

Methods. The study was conducted in eight rural districts and the city of Vladikavkaz, with a total population of 543,817 people. The population was examined in accordance with the protocol of genetic epidemiologic studies developed in RCMG. 11199 patients with congenital and presumptive OHDs were examined. The diagnosis of OHDs was made in 2115 patients from 1489 families. The genetic load (per 1000 people) of AD, AR, and X-linked diseases in urban and rural populations was estimated. Rates of genetic load values between populations were compared using the χ2 method. Pearson correlation analysis between genetic load values and measures of genetic structure was performed in Statistica v. 23.

Results. The genetic load of AD, AR, and X-linked pathology in rural populations (3.21; 2.45; 0.99, respectively) was almost twice as high as in urban populations (1.42; 1.52; 0.81). Variability in the magnitude of genetic load between populations was revealed. The maximum genetic load values were registered in Irafsky district (4.94 in the district center, 11.72 in the rural population), and the minimum in Vladikavkaz (2.69/1000). To explain the heterogeneity of the OHDs load, a correlation between the OHDs load and the genetic structure of 17 populations was carried out, which showed the leading role of genetic drift in the revealed differentiation. Significant coefficients >0.80 were obtained in all cases.

Conclusions. The obtained values of AD, AR and X-linked disease genetic load in RNOA populations are characterized by variability with a large range of values (2.96-11.72/1000). Such variability is characteristic of populations of small ethnic groups: in Karachay-Cherkessia (4.76-11.82/1000), in Tatarstan (5.20-11.70/1000), in Bashkortostan (3.83-9.08/1000) and others. In the regions with Russian population there is also a variation of the OHDs genetic load, but the absolute values are lower.

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