Exome-based search for recurrent disease-causing alleles in Russian population

Area of Science:

• Human Genetics
• Population Genetics
• Medical Genetics

Background:

• Genetic screening of diverse populations is crucial for understanding disease prevalence.
• Identifying medically relevant alleles aids in diagnosing and managing genetic disorders.
• Previous studies have not comprehensively analyzed the genetic landscape of medically relevant variants in the Russian population.

Purpose of the Study:

• To analyze exomes from Russian subjects for medically relevant alleles.
• To identify protein-truncating variants (PTVs) and pathogenic missense mutations.
• To assess the prevalence and persistence of these variants within the Russian population.

Main Methods:

• Whole exome sequencing of 27 Russian subjects.
• Identification of PTVs in known recessive disease genes and ClinVar pathogenic missense mutations.
• Analysis of 36 identified variants in 897 population controls.

Main Results:

• 36 medically relevant variants were identified, including 24 PTVs and 12 missense mutations.
• Two novel recurrent mutations were found: POLH c.490delG (xeroderma pigmentosum variant) and CATSPER1 c.859_860delCA (spermatogenic failure).
• Twenty pathogenic alleles demonstrated persistence in the Russian population, with specific examples including SERPINA1, C8B, ATP7B, and others.

Conclusions:

• The study identified significant medically relevant genetic variants in the Russian population.
• Persistence of several pathogenic alleles suggests their importance for genetic health in this population.
• These findings are valuable for future medical genetic activities and carrier screening in Russia.