BACKGROUND Previously, family-based designs and high-risk pedigrees have illustrated value for the discovery of high- and intermediate-risk germline breast cancer susceptibility genes. However, genetic heterogeneity is a major obstacle hindering progress. New strategies and analytic approaches will be necessary to make further advances. One opportunity with the potential to address heterogeneity via improved characterization of disease is the growing availability of multi-source databases. Specific to advances involving family-based designs are resources that include family structure, such as the Utah Population Database (UPDB). To illustrate the broad utility and potential power of multi-source databases, we describe two novel family-based approaches to reduce heterogeneity in the UPDB. METHODS Our first approach focuses on using pedigree-informed breast tumor phenotypes in gene mapping. Our second approach focuses on the identification of families with similar pleiotropies. We use a novel network-inspired clustering technique to explore multi-cancer signatures for high-risk breast cancer families. RESULTS Our first approach identifies a genomewide significant breast cancer locus at 2q13 (p=1.6x10-8, LOD equivalent 6.64). In the region, IL1A and IL1B are of particular interest, key cytokine genes involved in inflammation. Our second approach identifies five multi-cancer risk patterns. These clusters include expected co-aggregations (such as, breast with both prostate, ovarian, and melanoma), and also identify novel patterns, including uterine, thyroid, and bladder cancers. CONCLUSIONS Our results suggest pedigree-informed tumor phenotypes can map genes for breast cancer, and that various different cancer pleiotropies exist for high-risk breast cancer pedigrees. IMPACT Both methods illustrate the potential for decreasing etiological heterogeneity that large, population-based multi-source databases can provide. Copyright ©2020, American Association for Cancer Research.BACKGROUND Relatives of bladder cancer (BCa) patients have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multi-cancer configurations (multiple different cancer types that cluster in relatives) surrounding familial BCa patients. METHODS This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using Standardized Incidence Risk (SIR) ratios account for sex, age, birth-cohort, and person-years of the pedigree members. RESULTS We identify 1,023 families with a significantly higher BCa rates than population controls (fBCa). Familial SIRs are then calculated across twenty-five cancer-types and a weighted Gower distance with K-medoids clustering is used to identify Familial Multi-Cancer Configurations (FMC). We find five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial BCa clusters. Laryngeal, lung, stomach, acute-lymphocytic leukemia, Hodgkin's disease, soft tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial BCa families. CONCLUSIONS This study identified five familial BCa FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial BCa. IMPACT FMC configurations could permit better definitions of cancer phenotypes (subtypes or multi-cancer) for gene discovery and environmental risk factor studies. Copyright ©2020, American Association for Cancer Research.Eisenia fetida, the common vermicomposting earthworm, shows robust regeneration of posterior segments removed by amputation. During the period of regeneration, the newly formed tissue initially contains only undifferentiated cells but subsequently differentiates into a variety of cell types including muscle, nerve and vasculature. Transcriptomics analysis, reported previously, provided a number of candidate non-coding RNAs that were induced during regeneration. We found that one such long non-coding RNA (lncRNA) is expressed in the skin, only at the base of newly formed chaetae. The spatial organization and precise arrangement of the regenerating chaetae and the cells expressing the lncRNA on the ventral side clearly support a model wherein the regenerating tissue contains a zone of growth and cell division at the tip and a zone of differentiation at the site of amputation. The temporal expression pattern of the lncRNA, christened Neev, closely resembled the pattern of chitin synthase genes, implicated in chaetae formation. We found that the lncRNA harbours 49 sites for binding a set of four miRNAs while the Chitin Synthase 8 mRNA comprises 478 sites. The over-representation of shared miRNA sites suggests that lncRNA Neev may act as a miRNA sponge to transiently de-repress chitin synthase 8 during formation of new chaetae in the regenerating segments of Eisenia fetida. © 2020. Published by The Company of Biologists Ltd.Predicting the sensitivity of reef-building corals to disturbance, including bleaching, requires an understanding of physiological responses to stressors, which may be limited by destructive sampling and the capacity of common methodologies to characterize early life history stages. https://www.selleckchem.com/products/e7449.html We developed a new methodology using laser scanning confocal microscopy (LSCM) to measure and track the physiological condition of corals. In a thermal stress experiment, we used LSCM to track coral condition during bleaching in adults and juveniles of two species, Montipora capitata and Pocillopora acuta Depth of fluorescence in coral tissues provides a proxy measure of tissue thickness, whereas Symbiodiniaceae population fluorescence relates to both population density and chlorophyll a content. In response to thermal stress, there were significant shifts in tissue thickness and Symbiodiniaceae fluorescence with differences between life stages. This method is particularly well suited for detecting shifts in physiological condition of living corals in laboratory studies, especially in small juvenile colonies.