Social interactions and the overall psychosocial environment have a demonstrated impact on health, particularly for people living in disadvantaged urban areas. Here we investigated the effect of psychosocial experiences on gene expression in peripheral blood immune cells of children with asthma in Metro Detroit. Using RNA-sequencing and a new machine learning approach, we identified transcriptional signatures of 19 variables including psychosocial factors, blood cell composition and asthma symptoms. Importantly, we found 169 genes associated with asthma or allergic disease that are regulated by psychosocial factors, and 344 significant gene-environment interactions for gene expression levels. These results demonstrate that immune gene expression mediates the link between negative psychosocial experiences and asthma risk.
The data are available on dbGAP. Accession number: phs002182.v1.p1.
- Samuele Zilioli
- Richard B Slatcher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Participants were included from an ongoing longitudinal study, Asthma in the Lives of Families Today (ALOFT; recruited from November 2010-July 2018, Wayne State University Institutional Review Board approval #0412110B3F).
- Patricia W Finn, University of Illinois at Chicago, United States
© 2021, Resztak et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic ΔG-Rabies has been widely used in neuroscience research. A recently developed engineered version of the ΔG-Rabies, the non-toxic self-inactivating (SiR) virus, allows the long term genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical ΔG-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiR in vitro and in vivo. We found that “revertant” mutations are rare and accumulate only when SiR is extensively amplified in vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical ΔG-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emerge in vivo during long-term experiments.
Quantitative traits are often complex because of the contribution of many loci, with further complexity added by environmental factors. In medical research, systems genetics is a powerful approach for the study of complex traits, as it integrates intermediate phenotypes, such as RNA, protein, and metabolite levels, to understand molecular and physiological phenotypes linking discrete DNA sequence variation to complex clinical and physiological traits. The primary purpose of this review is to describe some of the resources and tools of systems genetics in humans and rodent models, so that researchers in many areas of biology and medicine can make use of the data.