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PLOS Papers on Pharmacogenes in Hong Kong, Defective Viral Genomes, Brazilian Breast Cancer

In PLOS Genetics, a team led by investigators at the University of Hong Kong takes a look at the range of actionable pharmacogenetic variants found in exome-sequenced individuals from a Chinese population in Hong Kong. Starting with exome sequences for more than 1,100 individuals with Southern Chinese ancestry from Hong Kong, the researchers searched for 133 actionable pharmacogenetic variants or rare deleterious alterations affecting 108 genes previously annotated as 'high-confidence pharmacogenes,' uncovering just over two dozen actionable pharmacogenetic variants in 15 genes, along with four drug response-related human leukocyte antigen alleles. "The findings demonstrated the potential of pharmacogenetic testing in improving patient care and resource allocation in Chinese," the authors write, adding that the available data "supports clinical implementation of pharmacogenetics in the Chinese population."

Researchers from France, the Czech Republic, and the US report on an apparent role for altered viral genomes that arise during replication — dubbed defective viral genomes (DVGs) — in stunting Chikungunya virus (CHIKV) spread by Aedes aegypti mosquitoes for a paper in PLOS Pathogens. Using experimental evolution experiments and computational analyses, the team saw signs that truncated or rearranged DVGs interfere with normal CHIKV replication in in vitro-infected mammalian cells or in vivo experiments in Ae. aegypti, suggesting that it may be possible to deter some infectious disease spread by treating susceptible mosquitoes with DVGs. "We confirm [DVG] antiviral activity in both mammalian and mosquito host environments and show that some can broadly interfere with other strains or related alphaviruses," the authors write, adding that the DVGs also appear to inhibit virus dissemination in mosquitoes."

For a paper in PLOS One, investigators in Brazil outline hereditary breast cancer findings found through a retrospective analysis of gene panel sequencing, single gene, or family variant test data for more than 200 Brazilian breast cancer patients referred for genetic counseling and testing over two years at a tertiary oncology center in Brazil's capital Brasília. Of the 224 women included in the study, nearly 69 percent were premenopausal, the team notes, and some 85 percent met available criteria for hereditary breast cancer testing. The authors report that more than one in five patients profiled carried a germline pathogenic variant (PV), with hereditary cancer risk variants turning up in 13 genes, including high-penetrance genes such as BRCA1, BRCA2, and PALB2. "In our study," the authors conclude, "[breast cancer] prior to 45 years, multiple primary cancers, high-grade tumors, bilateral [breast cancer], and a family history of pancreatic cancer were features associated with a higher probability of PV detection."