BRCA1 c.68_69del as a founder variant in the Spanish Roma: prevalence and screening implications

Area of Science:

• Genetics
• Population Genetics
• Medical Genetics

Background:

• The BRCA1 c.68_69del variant is prevalent in Ashkenazi Jewish populations, where genetic screening is cost-effective.
• Understanding the prevalence and origin of this variant in other populations, like the Roma, is crucial for genetic screening strategies.

Purpose of the Study:

• To investigate the prevalence of the BRCA1 c.68_69del variant in Spanish Roma individuals.
• To determine the origin of the BRCA1 c.68_69del variant in the Roma population through haplotype analysis.

Main Methods:

• Conducted two cross-sectional prevalence studies in self-reported Roma adults.
• Reconstructed haplotypes in carriers with Roma, Indian, Ashkenazi Jewish, and European ancestry.
• Compared haplotype sharing and mutation-age estimates to assess variant origin.

Main Results:

• The BRCA1 c.68_69del variant was detected in 3.6% of a community-based Roma sample and 0.8% of a nationwide Roma sample.
• Roma carriers shared extended haplotypes with European and Ashkenazi Jewish carriers, suggesting a common founder.
• Mutation-age estimates indicated an Iberian founder origin, later enriched in the Roma population.

Conclusions:

• The BRCA1 c.68_69del variant has a high prevalence in Spanish Roma due to an Iberian founder effect.
• These findings support the implementation of targeted genetic screening for the BRCA1 c.68_69del variant within the Spanish Roma community.