Biology subjects

Bailey, J. A.

Publications and source records attributed to Bailey, J. A..

21 records · Page 2Linked to original sources

bioRxiv2019

Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71, P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.\n\nKey PointsO_LIEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.\nC_LIO_LIGenome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.\nC_LIO_LIAnalysis of population structure reveals that EBV type 2 exists as two genomic sub groups.\nC_LI

genomics↗

bioRxiv2019

The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

genomics↗

bioRxiv2018

Loss of cytoplasmic incompatibility and minimal fecundity effects explain relatively low Wolbachia frequencies in Drosophila mauritiana

Maternally transmitted Wolbachia bacteria infect about half of all insect species. Many Wolbachia cause cytoplasmic incompatibility (CI), reduced egg hatch when uninfected females mate with infected males. CI produces a frequency-dependent fitness advantage that leads to high equilibrium Wolbachia frequencies but does not aid Wolbachia spread from low frequencies. The fitness advantages that produce initial Wolbachia spread and maintain non-CI Wolbachia remain elusive. Wolbachia variant wMau that infects Drosophila mauritiana does not cause CI, despite being very closely related to the CI-causing Wolbachia wNo in D. simulans (0.068% sequence divergence over 682,494 bp), suggesting that CI was recently lost. Using draft Wolbachia genomes, we identify a deletion in a WO phage gene that may disrupt CI. We find no evidence that wMau increases host fecundity. We report intermediate and apparently stable wMau infection frequencies on the Indian Ocean island of Mauritius, consistent with no CI and no appreciable positive effect on fecundity. Our data indicate that wMau frequencies reflect a balance between unknown, weak positive effects on fitness and imperfect maternal transmission. Phylogenomic analyses suggest that Supergroup B Wolbachia, including wMau, diverged from Supergroup A Wolbachia, including wMel from D. melanogaster, 6-46 million years ago, later than previously estimated.

evolutionary biology↗