What is the main rationale for targeted testing of founder mutations in certain populations?

• A. It guarantees detecting all pathogenic variants.
• B. It has no clinical utility.
• C. It replaces full sequencing globally.
• D. It reduces testing costs by focusing on common variant regions in the target population, potentially missing rare variants.

Answer: (D)

Targeted testing leverages founder mutations in populations with shared ancestry. In these groups, a substantial portion of hereditary cancer risk comes from a small set of recurrent variants that arose in a common ancestor and became relatively common over generations. By focusing testing on these known, high-frequency variants, laboratories can test more efficiently—reducing cost, turnaround time, and the need for broader resources—while still capturing the majority of clinically meaningful mutations in that specific population. This approach maximizes yield where prior data show these recurrent mutations drive risk, making screening practical and affordable in resource-limited or high-demand settings. The trade-off is that rare or novel variants outside the targeted panel may be missed, so targeted testing does not replace comprehensive sequencing when a full assessment is warranted.