Comprehensive Annotation of Bidirectional Promoters Identifies Co-Regulation among Breast and Ovarian Cancer Genes

A “bidirectional gene pair” comprises two adjacent genes whose transcription start sites are neighboring and directed away from each other. The intervening regulatory region is called a “bidirectional promoter.” These promoters are often associated with genes that function in DNA repair, with the potential to participate in the development of cancer. No connection between these gene pairs and cancer has been previously investigated. Using the database of spliced-expressed sequence tags (ESTs), we identified the most complete collection of human transcripts under the control of bidirectional promoters. A rigorous screen of the spliced EST data identified new bidirectional promoters, many of which functioned as alternative promoters or regulated novel transcripts. Additionally, we show a highly significant enrichment of bidirectional promoters in genes implicated in somatic cancer, including a substantial number of genes implicated in breast and ovarian cancers. The repeated use of this promoter structure in the human genome suggests it could regulate co-expression patterns among groups of genes. Using microarray expression data from 79 human tissues, we verify regulatory networks among genes controlled by bidirectional promoters. Subsets of these promoters contain similar combinations of transcription factor binding sites, including evolutionarily conserved ETS factor binding sites in ERBB2, FANCD2, and BRCA2. Interpreting the regulation of genes involved in co-expression networks, especially those involved in cancer, will be an important step toward defining molecular events that may contribute to disease

The Many Facets of Genetic Literacy: Assessing the Scalability of Multiple Measures for Broad Use in Survey Research

Objectives To determine how three dimensions of genetic literacy (familiarity, skills, and factual knowledge) fit the hierarchy of knowledge outlined in E.M. Rogers’ Diffusion of Innovations to better conceptualize lay understandings of genomics. Methods A consumer panel representing the US adult population (N = 1016) completed an electronic survey in November 2013. Adjusting for education, we used correlations, principle components analysis, Mokken Scale tests, and linear regressions to assess how scores on the three genetic literacy sub-dimensions fit an ordered scale. Results The three scores significantly loaded onto one factor, even when adjusting for education. Analyses revealed moderate strength in scaling (0.416, p\u3c0.001) and a difficulty ordering that matched Rogers’ hierarchy (knowledge more difficult than skills, followed by familiarity). Skills scores partially mediated the association between familiarity and knowledge with a significant indirect effect (0.241, p\u3c0.001). Conclusion We established an ordering in genetic literacy sub-dimensions such that familiarity with terminology precedes skills using information, which in turn precedes factual knowledge. This ordering is important to contextualizing previous findings, guiding measurement in future research, and identifying gaps in the understanding of genomics relevant to the demands of differing applications

Addressing diversity and inclusion challenges in global neuro-psychiatric and behavioral genomics research

Advancements in neuro-psychiatric and behavioral genomics offer significant opportunities for better understanding the human brain, behavior and associated disorders. Such advancements may help us prevent, manage and/or cure complex conditions. The serious challenge confronted by these disciplines however is diversity. Both fields lack diversity in terms of genomic reference datasets needed for discovery research, engagement of diverse communities in translational research and in terms of diverse and multidisciplinary scientific teams. This is a challenge because diversity is needed on all levels in order to increase representation and inclusion of all populations across the globe as we move research activities forward. The lack of diversity can translate to an inability to use scientific innovations from these fields for the benefit of all people everywhere and signifies a missed opportunity to address pervasive global health inequities. In this commentary we identify three persistent barriers to reaching diversity targets while focusing on discovery and translational science. Additionally, we propose four suggestions on how to advance efforts and rapidly move towards achieving diversity and inclusion in neuro-psychiatric and behavioral genomics. Without systematically addressing the diversity gap within these fields, the benefits of the science may not be relevant and accessible to all people

Cultural diversity is crucial for African neuroethics

Mental health, neuroscience and neuroethics researchers must engage local African communities to enable discourses on cultural understandings of mental illness. To ensure that these engagements are both ethical and innovative, they must be facilitated with cultural competence and humility, because serious consideration of different contextual and local factors is critical

Sitting time and health outcomes among Mexican origin adults: obesity as a mediator

Background: Sitting time and sedentary behaviors have been associated with adverse health outcomes including obesity, diabetes and cardiovascular disease (CVD) within non- Hispanic White populations. Similar associations have not been described within Hispanic populations despite their high CVD risk profile. This study aimed to assess the association between sitting time and obesity, self-reported diagnosed diabetes, hypertension and high cholesterol among a large cohort (N=11,268) of Mexican origin adults and to assess whether obesity mediated these associations. Methods: Using a cross-sectional design, data collected between 2004 and 2010 were analyzed in late 2010. Regression analyses evaluated associations between self-reported daily sitting hours and disease outcomes, controlling for demographics, employment status, family disease history, and light, moderate and strenuous physical activity. Results: Participants were mostly female (81.1%) Mexican origin adults. Sitting time was associated with increased odds of being obese, having diabetes and having hypertension, but not high cholesterol. Adjusted odds ratios of participants who reported sitting > 4 hours/day compared to those sitting 1-2 hours/day were for obesity OR=1.55 (95% CI 1.39, 1.73), p<.001, for diabetes OR=1.29 (95% CI, 1.09, 1.52), p=.003, for hypertension OR=1.17 (95% CI, 1.01, 1.37), p=.041. Associations controlled for physical activity and employment status. Effects on hypertension and diabetes were mediated by obesity. Conclusions: Sitting time was significantly associated with detrimental health outcomes, independent of physical activity. Obesity mediated these relationships for diabetes and hypertension. Future research should assess whether interventions addressing sitting time are feasible and effective among Mexican origin populations

Beliefs About Cancer and Diet among Those Considering Genetic Testing for Colon Cancer

To assess beliefs about the role of diet in cancer prevention among individuals considering genetic testing for Lynch Syndrome