Publications

This study explored the experiences of young Jamaican men who have sex with men who engaged in transactional sex as a result of homelessness, family neglect or limited financial resources. It further examined the circumstances that affect their immediate or delayed decisions around sexual risk and increased vulnerability for HIV infection. Barriers experienced when accessing condoms, healthcare, HIV testing and other prevention services are also described. Twenty in-depth interviews and one focus group with 10 participants in various parishes in Jamaica were conducted. Findings from this study reveal how stigma and discrimination in the form of pervasive homophobia-influenced participation in the street economy via transactional sex. Socio-structural factors at family and commity level led to diminished social/economic prospects, which extended into adulthood. Sexual decision making was based on immediate needs for protection, food or shelter; concerns about acquiring HIV were considered only after meeting those immediate needs. Future HIV prevention strategies must take seriously the socio-structural factors that influence HIV risk behaviours among young men who have sex with men in Jamaica.

While genetic variants are known to be associated with overall gene abundance in stimulated immune cells, less is known about their effects on alternative isoform usage. By analyzing RNA-seq profiles of monocyte-derived dendritic cells from 243 individuals, we uncovered thousands of unannotated isoforms synthesized in response to influenza infection and type 1 interferon stimulation. We identified more than a thousand quantitative trait loci (QTLs) associated with alternate isoform usage (isoQTLs), many of which are independent of expression QTLs (eQTLs) for the same gene. Compared with eQTLs, isoQTLs are enriched for splice sites and untranslated regions, but depleted of sequences upstream of annotated transcription start sites. Both eQTLs and isoQTLs explain a significant proportion of the disease heritability attributed to common genetic variants. At the locus, we shed light on the function of the gene and how two frequent, highly differentiated haplotypes with intermediate frequencies could be maintained by balancing selection. At baseline and following type 1 interferon stimulation, the major haplotype is associated with low expression caused by nonsense-mediated decay, while the minor haplotype, known to increase Crohn's disease risk, is associated with high expression. In response to influenza infection, we found two uncharacterized isoforms expressed from the major haplotype, likely the result of multiple perfectly linked variants affecting the transcription and splicing at the locus. Thus, genetic variants at a single locus could modulate independent gene regulatory processes in innate immune responses and, in the case of , may confer a historical fitness advantage in response to virus.