The Prophet's mother carried gene-markers whose supreme importance to the breeding program was known for… — Frank Herbert

The Prophet's mother carried gene-markers whose supreme importance to the breeding program was known for almost two thousand years. She was a Bene Gesserit bred and trained, and should have been a willing tool of the project...Instead, for reasons she confesses have never been completely clear to her, the concubine Lady Jessica defied her orders and bore a son.

This alone should have alerted the Bene Gesserit to the possibility that a wild variable had entered their scheme.

Source: Wikiquote · CC BY-SA 4.0