What is the founder effect in BRCA testing among Ashkenazi Jews?

• A. BRCA mutations are distributed evenly; full sequencing required.
• B. A small number of ancestors contributed a large portion of BRCA variants; targeted screening for the three common Ashkenazi BRCA mutations is efficient.
• C. Founder effect means mutations only appear in Ashkenazi populations.
• D. The three common mutations are irrelevant to screening.

Answer: (B)

A founder effect happens when a population originates from a small number of ancestors, causing certain genetic variants to be more common in that group than in the general population. In Ashkenazi Jews, historical population bottlenecks led to a concentration of three BRCA mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. Because these specific mutations occur much more frequently in this population, testing for just these three variants detects most BRCA carriers efficiently and cost-effectively, making targeted screening a preferred first step. If someone tests negative but has a strong family history or other risk factors, a full BRCA1/BRCA2 sequencing can be considered. The other options aren’t correct because the mutations aren’t evenly distributed across all populations, they aren’t exclusive to Ashkenazi Jews, and these mutations are relevant to screening in this group.