Детальная информация

The work is devoted to identifying rare coding variants that may underlie hereditary diseases in an isolated Dagestan population, where endogamy, limited gene flow, and founder effects increase the likelihood of recurrent recessive alleles. The study used exome sequencing of 31 unrelated, phenotypically healthy Avars as a discovery cohort, followed by genotyping in 192 healthy Avar controls to estimate allele frequencies.  Variants were filtered for rarity and predicted functional impact, then prioritized using clinical databases, literature data, inheritance pattern, phenotype plausibility, and Sanger validation. As a result, 66 candidate variants were initially identified, recurrent loci were highlighted as potential founder signals, and several variants were excluded because they were not confirmed or required technical optimization.    The results clarify the genetic architecture of rare Avar pathologies and can be applied in genetic counseling, ethnospecific screening, and the search for phenotype-matched patient cohorts. The study shows that exome sequencing is an effective first-stage approach for founder populations, while final causal interpretation requires additional clinical confirmation.