Epidemiology of Hereditary Diseases in the Karachay-Cherkess Republic.

Rena A Zinchenko,Lyudmila K Mikhailova,Polina Gundorova,Andrey V Marakhonov,Elena L Dadali,Amin Kh Makaov,Eugeny K Ginter,Nika V Petrova,Sergey I Kutsev,Tatyana A Vasilyeva,Nina E Petrina,Varvara A Galkina,Vitaly V Kadyshev,Alexander V Polyakov,Oksana Y Alexandrova,Galina I El’Chinova

doi:10.3390/ijms21010325

Rena A Zinchenko, Lyudmila K Mikhailova + Show 14 more

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https://doi.org/10.3390/ijms21010325

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Abstract

Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in different modern open populations is important. The study presents the results of a genetic epidemiological study of hereditary diseases (HDs) in the population of the Karachay-Cherkess Republic (KChR). Clinical screening of a population of 410,367 people for the identification of HDs was conducted. The population surveyed is represented by five major ethnic groups—Karachays, Russians, Circassians, Abazins, Nogais. The study of the populations was carried out in accordance with the proprietary protocol of genetic epidemiological examination designed to identify >3500 HDs easily diagnosed during clinical examination by qualified specialists specializing in the HDs. The protocol consists of the population genetic and medical genetic sections and is intended for comprehensive population analysis based on the data on different genetic systems, including the genes of HDs, DNA polymorphisms, demographic data collected during hospital-based survey. 8950 families (with 10,125 patients) with presumably the HDs were initially identified as a result of the survey and data collection through various sources of registration (from 1156 medical workers from 163 medical institutions). A diagnosis of hereditary pathology was established in 1849 patients (from 1295 families). Two hundred and thirty nosological forms were revealed (in 1857 patients from 1295 families). The total prevalence of HDs was 1:221. Differences between populations and ethnic groups were identified: 1:350 in Russians, 1:195 in Karachays, 1:199 in Circassians, 1:218 in Abazins, 1:135 in Nogais. Frequent diseases were determined, the presence of marked genetic heterogeneity was identified during the confirmatory DNA diagnosis. To explain the reasons for the differentiation of populations by load of HD, a correlation analysis was carried out between the FST (random inbreeding) in populations and HDs load values. This analysis showed genetic drift is probably one of the leading factors determining the differentiation of KChR populations by HDs load. For the first time, the size of the load and spectrum of HDs in the populations of the KChR are determined. We have demonstrated genetic drift to be one of the main factors of the population dynamics in studied population. A significant genetic heterogeneity of HDs, both allelic and locus, was revealed in KChR.

Highlights

Genetic differentiation of human populations and its mechanisms remain the key problem of ethno-genetics and population genetics and became a clue for the understanding the intensity and direction of microevolution process in different ethnic groups
The analysis of our work has shown that the card questionnaire works best in rural populations, identifying more than 80% of all patients with the NB, as the medical staff is well informed about all patients at their site
The carried out studies have made it possible for the first time to determine the size of the load and spectrum of hereditary diseases characteristic of the populations of the Karachay-Cherkess Republic and for the main ethnic groups living in the territory

Summary

Introduction

Genetic differentiation of human populations and its mechanisms remain the key problem of ethno-genetics and population genetics and became a clue for the understanding the intensity and direction of microevolution process in different ethnic groups. Information about the load and diversity of HDs obtained in particular ethnic groups could not be used for general considerations as well as for extrapolation to other populations. Load of accumulated specific and frequent HDs were identified in populations of Finns [6], Ashkenazi Jews [7], Amish from the USA [8], French Canadians [9,10] and some others. These studies demonstrated the role of the genetic structure and the influence of factors of population dynamics on the formation of the load and diseases specific to these populations. The global, predominantly European, prevalence of some nosological forms is currently covered in the annual report of the Orphanet Reports Series and in OMIM (Online Mendelian Inheritance in Man) [11]

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