The global colonization by Europeans in recent hundreds of years resulted in the most widespread admixture in human history. The Portuguese global exploration provides a typical example of human admixture. Initiated in the 15th century, the Portuguese established its colonies across Africa, Asia and America including the countries of Angola, Mozambique, India, Sri Lanka, Malaya, China, Japan, East Timor and Brazil etc. In many of the places colonized by the Portuguese, admixture formed between Portuguese and locals. Up to now, there are over 20 million Portuguese-heritage population worldwide in comparing to the 10.3 million native Portuguese in Portugal. In Brazil alone, there are around five-million individuals with Portugal heritage, constituting 2.3% of Brazil population. Biomedically, human admixture may enhance genetic diversity, but may also transfer disease risk between populations. The population with Portuguese heritage provides a valuable model to study the impact of admixture on human health.
Genomic DNA in the genome is constantly damaged by external and internal factors. The damaged DNA must be repaired in order to prevent genome instability, which causes disease risk. This function is achieved by the DNA damage repair (DDR) system, consisting of multiple pathways and hundreds of different genes, BRCA1 and BRCA2 are two important genes for repairing double-strand DNA breaks through the homology recombination pathway. However, DDR genes are prone to genetic variation. These with pathogenic effects can damage the function of the affected genes, leading to disease risk. For example, women carrying pathogenic variants in BRCA1 have a 55%–72% lifetime risk of developing breast cancer and 39%–44% lifetime risk of developing ovarian cancer, and these carrying pathogenic variants in BRCA2 have a 45%–69% risk of developing breast cancer and 11%–17% lifetime risk of developing ovarian cancer. Identification of BRCA pathogenic variant carriers without cancer can prevent cancer development by taking preventive measures of early cancer surveillance, chemoprevention and preventive surgery, and Identification of BRCA pathogenic variant carriers with cancer can benefit the use of targeted treatment such as PARP inhibitors to treat the cancer.
BRCA variation has been comprehensively characterized in the Portuguese population and the Brazilian population. In this study, we used the pathogenic variation of BRCA in Portuguese and Brazilian populations as a model to study the impact of admixture on human health. We performed a comprehensive collection, standardization and classification of the BRCA variation data originated from Portuguese and Brazilian populations, and constructed the centralized Portuguese and Brazilian BRCA databases. By tracing the Portuguese-originated BRCA variation in Brazilian population, we observed the half of the Portuguese-originated BRCA pathogenic variation are present in Brazilian population, as represented by the Portuguese founder variants BRCA1 c.3331_3334del, BRCA1 c.2037delinsCC, and BRCA2 c.156_157insAlu.
Data from our study show that admixture can impact on human health by introducing pathogenic variation from donor to recipient population.