Affiliation:
1. MoE Frontiers Science Center for Precision Oncology, Cancer Center and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, China
Abstract
BRCA1 and BRCA2 (BRCA) play essential roles in maintaining genome stability. BRCA germline pathogenic variants increase cancer risk. However, the evolutionary origin of human BRCA pathogenic variants remains largely elusive. We tested the 2,972 human BRCA1 and 3,652 human BRCA2 pathogenic variants from ClinVar database in 100 vertebrates across eight clades, but failed to find evidence to show cross-species evolution conservation as the origin; we searched the variants in 2,792 ancient human genome data, and identified 28 BRCA1 and 22 BRCA2 pathogenic variants in 44 cases dated from 45,000 to 300 yr ago; we analyzed the haplotype-dated human BRCA pathogenic founder variants, and observed that they were mostly arisen within the past 3,000 yr; we traced ethnic distribution of human BRCA pathogenic variants, and found that the majority were present in single or a few ethnic populations. Based on the data, we propose that human BRCA pathogenic variants were highly likely arisen in recent human history after the latest out-of-Africa migration, and the expansion of modern human population could largely increase the variation spectrum.
Funder
Macau Science and Technology Development Fund
University of Macau
Publisher
Life Science Alliance, LLC
Subject
Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology
Cited by
19 articles.
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