EARLIER AGE OF ONSET IN BRCA CARRIERS

carriers—anticipation or cohort effect? A Countercurrents Seriesa with S.A. Narod md because each generation contains a mix of first-gener-ation carriers, second-generation carriers, and so on. It is believed that, eventually, the age of onset becomes young enough that reproductive fitness is impaired, and the most harmful alleles are thereby lost in the population (and are replenished by de novo mutations). In a cohort effect, penetrance of the gene depends on the year of birth of the carriers. When a cohort effect is present, a decline in age at diagnosis with subsequent generations within a pedigree is also observed, but the average age at diagnosis in the underlying populatio