GENETIC LOAD IN HUMAN POPULATIONS THROUGH THE PRISM OF LOCAL INBREEDING

Abstract

Вackground. Assessing genetic load is relevant in connection with active migration and population decline, especially in combat zones. This study aimed to analyse the dynamics of genetic disorder prevalence depending on demographic characteristics in Eastern Ukraine.
Materials and Methods. A cross-sectional population-based impersonal study was performed in four districts of the Kharkiv region as a typical area of Eastern Ukraine. The mean age, mean migration distance, and marital distance of women aged up to 45 years and men aged up to 55 years were assessed from district marriage records of the year 2015. The prevalence of genetic disorders among children aged 0–17 years was estimated based on district medical registries. The genetic structure of the population was estimated through the local inbreeding coefficient F_ST.
Results and Discussion. Data for 1427 marriages and 187 children with genetic disor­ders were analysed. The mean age at marriage, mean migration distance, and marital distance were 27.8 ± 0.1 years, 179.0 ± 15.0 km, and 320.4 ± 28.4 km. F_st accounted for 0.000074–0.012949 and was up to 17.2 times greater (p = 0.0012) in rural areas than in urban ones. The overall F_st across four districts was 0.001292, representing a 1.8-fold increase (p = 0.001477) over seven years. The prevalence of 39 single-gene and 4 chromosome disorders was 0.36 % and 0.08 %, with a positive trend over time. The most common disorders were sensorineural hearing loss (1 : 859), isolated growth hormone deficiency (1 : 3438), ichthyosis vulgaris (1 : 3750), cystic fibrosis (1 : 6875), and Down syndrome (1 : 1331). The prevalence of single-gene disorders in rural populations was 4.3 times greater than in urban ones – 1.29 % and 0.30 % (р = 0.007). F_st was positively correlated with the prevalence of autosomal recessive disorders (r = 0.82, p < 0.001) and chromosomal abnormalities (ρ = 0.90, p < 0.001).
Conclusion. In the region of study, an upward trend was observed in the inbree­ding coefficient (F_st), which has doubled across both urban and rural settlements over a seven-year period, reaching a value of 0.001292. This rise in local inbreeding is associated with an increased genetic load within the population, particularly concerning not only single-gene, but also chromosomal pathologies abnormalities. Both urban and rural populations exhibited a wide spectrum of genetic disorders, comprising 39 single-gene nosological entities and 4 chromosomal ones. When forecasting healthcare and social support needs, it is advisable to take into account the higher prevalence rates of genetic disorders in rural areas.