BRCA1/2 potential founder variants in the Jordanian population: an opportunity for a customized screening panel

AbstractA founder variant is a genetic alteration, that is inherited from a common ancestor together with a surrounding chromosomal segment, and is observed at a high frequency in a defined population. This founder effect occurs as a consequence of long-standing inbreeding of isolated populations. For high-risk cancer predisposition genes, such asBRCA1/2, the identification of founder variants in a certain population could help designing customized cost-effective cancer screening panels. This advantage has been best utilized in designing a customized breast cancerBRCA screening panel for the Ashkenazi Jews (AJ) population, composed of the threeBRCA founder variants which account for approximately 90% of identifiedBRCA alterations. Indeed, the high prevalence of pathogenicBRCA1/2 variants among AJ (~  2%) has additionally contributed to make population-based screening cost-effective in comparison to family-history-based screening. In Jordan there are multiple demographic characteristics supporting the proposal of a founder effect. A high consanguinity rate of ~ 57% in the nineties of the l ast century and ~ 30% more recently is a prominent factor, in addition to inbreeding which is often practiced by different sub-populations of the country.This review explains the concept of founder effect, then applies it to analyze published JordanianBRCA variants, and concludes that nine pathogenic (P) and likely pathogenic (LP)BRCA2 variants together with one pathogenicBRCA1 var...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research