Mapping mitonuclear epistasis using a novel recombinant yeast population.

Genetic variation in mitochondrial and nuclear genomes can perturb mitonuclear interactions and lead to phenotypic differences between individuals and populations. Despite their importance to most complex traits, it has been difficult to identify the interacting mitonuclear loci. Here, we present a novel advanced intercrossed population of Saccharomyces cerevisiae yeasts, called the Mitonuclear Recombinant Collection (MNRC), designed explicitly for detecting mitonuclear loci contributing to complex traits. For validation, we focused on mapping genes that contribute to the spontaneous loss of mitochondrial DNA (mtDNA) that leads to the petite phenotype in yeast. We found that rates of petite formation in natural populations are variable and influenced by genetic variation in nuclear DNA, mtDNA and mitonuclear interactions. We mapped nuclear and mitonuclear alleles contributing to mtDNA stability using the MNRC by integrating a term for mitonuclear epistasis into a genome-wide association model. We found that the associated mitonuclear loci play roles in mitotic growth most likely responding to retrograde signals from mitochondria, while the associated nuclear loci with main effects are involved in genome replication. We observed a positive correlation between growth rates and petite frequencies, suggesting a fitness tradeoff between mitotic growth and mtDNA stability. We also found that mtDNA stability was correlated with a mobile mitochondrial GC-cluster that is present in certain populations of yeast and that selection for nuclear alleles that stabilize mtDNA may be rapidly occurring. The MNRC provides a powerful tool for identifying mitonuclear interacting loci that will help us to better understand genotype-phenotype relationships and coevolutionary trajectories.

Development and Evaluation of Patient Navigation Training for Rural and Appalachian Populations.

The Appalachian region of the USA includes 423 counties in 13 states positioned along the spine of the Appalachian Mountains stretching from New York to Mississippi. Approximately 42% of Appalachia is rural, and while the economy of Appalachia has diversified over the past two decades from reliance on agriculture and coal mining, 176 (41.6%) of the 423 counties are classified as economically distressed or at-risk. Patient navigation (PN) has been shown to be effective as an approach to address multiple barriers and enhance access to healthcare services, and yet there are no known PN programs focusing on the Appalachian population. This project was designed to develop, implement, and evaluate a curriculum and training program for PN for cancer prevention and control in Appalachia. The training program was developed through formative evaluation and offered daylong workshops that provided instruction in 60-90-min modules. Workshop topics included an introduction to PN, Appalachian culture, community needs assessment, communication, financial navigation, and navigation for screening and diagnostic follow-up for breast, cervical, and colorectal cancers. A total of 20 workshops were conducted with 334 attendees. The workshops were evaluated using a mixed-method approach using pre- and posttests and participant evaluations. The overall mean posttest scores increased by 4% from pretest (p < 0.05). Evaluation also showed that attendees valued the focus on Appalachian culture and judged the content relevant and useful. Attendees also expressed interest in additional opportunities for similar workshops that expanded upon current topics and allowed for exploration of Appalachian health-related issues.