Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment

Background: Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants.

Results: First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements.

Conclusions: The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease.

Contemporary and 'messy' rural in-migration processes: Comparing counterurban and lateral rural migration.

This paper questions the ongoing dominant coverage given to counterurbanisation in the rural population literature. It is argued that this provides only a partial account of the true diversity of contemporary migration processes operating in rural areas and has the potential to fuse together different in-migration processes. Specifically, lateral rural migration has been under-researched to date. Using empirical data from a survey of 260 migrant households to 3 UK case study areas (in Scotland, Wales, and Northern Ireland), the significance of lateral rural migration is revealed and compared with counterurban migration and migrants. The last change of address shows that 59% relocated from an urban area (participating in a counterurban flow) whilst 41% moved from another rural location (lateral rural flow). The boundary between migration processes can, however, be blurred: Some moves are an example of both counterurbanisation and lateral rural flows. Incorporating lifetime migration histories data demonstrates the contemporary complexity and messiness of rural in-migration processes. For example, 26% of these migrant households only ever undertook a lateral rural move during their lifetime. For others, the direction of migration has changed numerous times and intertwined with each move are aspects of life course, return, and inter-regional migration. Comparing the survey characteristics and motivations of counterurban and lateral rural migrants, alongside interview material, highlights important similarities and differences. The paper concludes by calling on rural population geographers to more fully engage with the complexity, totality, and indeed messiness of contemporary rural in-migration processes.