Project description:Purpose: Parts of Europe and the United States have witnessed dramatic losses in commercially managed honey bees over the past decade to what is considered an unsustainable extent. The large-scale loss of honey bees has considerable implications for the agricultural economy because honey bees are one of the leading pollinators of numerous crops. Honey bee declines have been associated with several interactive factors. Poor nutrition and viral infection are two environmental stressors that pose heightened dangers to honey bee health. Methods: We used RNA-sequencing to examine how monofloral diets (Rockrose and Chestnut) and Israeli acute paralysis virus inoculation influence gene expression patterns in honey bees. Results: We found a considerable nutritional response, with almost 2,000 transcripts changing with diet quality. The majority of these genes were over-represented for nutrient signaling (insulin resistance) and immune response (Notch signaling and JaK-STAT pathways). Somewhat unexpectedly, the transcriptomic response to viral infection was fairly limited. We only found 43 transcripts to be differentially expressed, some with known immune functions (argonaute-2), transcriptional regulation, and muscle contraction. We created contrasts to determine if any protective mechanisms of good diet were due to direct effects on immune function (resistance) or indirect effects on energy availability (tolerance). A similar number of resistance and tolerance candidate differentially expressed genes were found, suggesting both processes may play significant roles in dietary buffering from pathogen infection. We also compared the virus main effect in our study (polyandrous colonies) to that obtained in a previous study (single-drone colonies) and verified significant overlap in differential expression despite visualization methods showing differences in the noisiness levels between these two datasets. Conclusions: Through transcriptional contrasts and functional enrichment analysis, we add to evidence of feedbacks between diet and disease in honey bees. We also show that comparing results derived from polyandrous colonies (which are typically more natural) and single-drone colonies (which usually yield more signal) may allow researchers to identify transcriptomic patterns in honey bees that are concurrently less artificial and less noisy. Altogether, we hope this work underlines possible merits of using data visualization techniques and multiple datasets when interpreting RNA-sequencing studies. Overall design: Two factor RNA-sequencing experiment with four treatment groups (Rockrose pollen without IAPV exposure, Chestnut pollen without IAPV exposure, Rockrose pollen with IAPV exposure, and Chestnut pollen with IAPV exposure)
Project description:Leprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. Genetic association studies indicated that leprosy risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but the full number of variants in this region has yet to be elucidated. To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. The meta-analysis of Chinese participants identified 10 HLA-type or amino acid variants with lower than the genome-wide significant susceptibility signal. Next, gene-by-gene step-wise conditional analysis was performed in the combined dataset of these cohorts. Finally, we identified four new independent susceptibility loci (HLA-DQA1, HLA-C, rs3129063, and rs58327373) and confirmed one previously reported locus (HLA-DRB1) that significantly associated with leprosy in the Chinese Han population. Thus the results of this study increase knowledge about leprosy risk variants and illustrate the value of HLA imputation for fine mapping of causal variants in the MHC. Overall design: To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region (29–34 Mb at chromosome 6) using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. This series includes the 728 cases and 1276 controls hybridized on Illumina Human610-Quad BeadChip in GWAS 1.