Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants

Area of Science:

• Genetics
• Population Genetics
• Medical Genetics

Background:

• Ashkenazi Jewish (AJ) populations exhibit increased prevalence of recessive genetic disorders due to founder effects.
• While some disease-causing mutations are known, many require further characterization within this demographic.

Purpose of the Study:

• To determine the carrier frequencies of 85 pathogenic variants responsible for 29 distinct recessive conditions in the AJ population.
• To evaluate the necessity of including additional recessive genetic conditions in AJ carrier screening.

Main Methods:

• Genotyping of up to 3000 AJ individuals using Luminex MagPlex-TAG bead array or Agena Bioscience MassARRAY assays.
• Analysis of carrier frequencies for 85 specific pathogenic variants across 29 recessive diseases.

Main Results:

• Seven conditions showed carrier frequencies exceeding 1 in 100.
• Nine conditions had frequencies between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500.
• The combined carrier frequency for 18 prevalent diseases was 1 in 6, with a 1 in 441 risk for carrier couples.

Conclusions:

• Significant carrier frequencies for multiple recessive conditions exist in the AJ population.
• Current screening panels may not encompass all relevant recessive disorders for AJ individuals.
• Expansion of carrier screening panels is recommended for comprehensive genetic risk assessment in the AJ population.