Content and performance of the MiniMUGA genotyping array: A new tool to improve rigor and reproducibility in mouse research

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research

Sixteen-year follow-up of childhood avalanche survivors

Background: Every year a substantial number of children are affected by natural disasters worldwide. However, data are scarce on long-term psychological impact of natural disasters on children's health. Identifying risk factors and outcomes associated with the long-term sequelae of posttraumatic stress disorder (PTSD) can provide a gateway to recovery as well as enhancement of preventive measures. Objective: Among childhood avalanche survivors, we aimed to investigate risk factors for PTSD symptoms and the relationship between socioeconomic status (SES) and PTSD symptoms in adulthood. Methods: Childhood survivors (aged 2–19 at the time of exposure) of two avalanches were identified through nationwide registers 16 years later. The Posttraumatic Diagnostic Scale was used to assess current PTSD symptoms. One-way ANOVA was used to explore PTSD symptoms by background and trauma-specific factors, as well as associations with current SES. Predictors of PTSD symptoms were examined by multivariable regression analysis. Results: Response rate was 66% (108/163). Results from univariate ANOVA analysis revealed that female sex was associated with PTSD symptoms (F=5.96, p<0.05). When adjusted for age and sex, PTSD symptoms were associated with lower education (F=7.62, p<0.001), poor financial status (F=12.21, p<0.001), and unemployment and/or disability (F=3.04, p<0.05). In a multivariable regression model, when adjusting for age and sex, lack of social support (t=4.22, p<0.001) and traumatic reactions of caregivers (t=2.49, p<0.05) in the aftermath of the disaster independently predicted PTSD 16 years post-trauma. Conclusions: Lingering PTSD symptoms after childhood exposure to a disaster may negatively influence socioeconomic development in adulthood. Strengthening children's support systems post-disaster may prevent the long-term sequelae of symptoms. Highlights of the article PTSD symptoms following avalanche exposure during childhood were associated with poorer socioeconomic status in adulthood. Lack of social support and traumatic reactions of caregivers in the aftermath of avalanches predicted PTSD symptoms among childhood survivors 16 years later. Findings underscore the importance of strengthening children's support systems in the aftermath of disasters