This R24 proposal outlines both resource (Aims 1 and 2) and research (Aim 3) components designed to enhance the Xiphophorus Genetic Stock Center (XGSC) that has operated within the United States since the 1930's; making it one of the oldest live animal resource centers worldwide and a national scientific treasure. The XGSC currently houses 58 pedigreed genetic lines representing 24 Xiphophorus species of live-bearing fishes in over 1,400 aquaria. The XGSC has provided pedigreed fish and materials to researchers in over 30 laboratories representing 11 countries. The traditional strength of the Xiphophorus experimental model involves the non-biased assessment of genetic inheritance patterns associated with complex phenotypes. The high genetic variability among Xiphophorus species and capability of producing fertile interspecies hybrids allows inheritance of any observable trait to be followed into individual backcross hybrid progeny. For example, genetic control of tumor susceptibility has been documented in both pure strains and in select Xiphophorus interspecies hybrids, for a variety of spontaneous and induced neoplasms, including several genetically distinct types of melanoma. Proposed improvements to Xiphophorus genomic capabilities promises to support new fundamental knowledge regarding; (a) shifts in the global transcriptional state of cells within the intact organism, (b) complex gene interactions brought about by interspecies hybridization, (c) the genetics underlying melanoma susceptibility, and (d) the initiation and progression of tumorigenesis. Given our preliminary data, we have high expectations for novel scientific findings in the next project period. Specifically, the XGSC will continuing to provide the research community with animals, enhanced resources, and user databases related to the genetically managed lines, and complete cryopreservation of germplasm from all XGSC lines. Enhancements to the genome assemblies will be made by application of new optical mapping (BioNano) and extra-long sequencing (PacBio) technologies. Finally, we will establish basal gene expression profiles for major organs and determine the rate of genetic transduction through the organism after external stimulus.
Upgrades in genome assermblies of parental species provides tools needed for dissection of the genetics underlying melanoma susceptibility in this well establsihed vertebrate model. Basal gene expression profiles for multitple organs will allow determination of genetic transduction from an external stimulus through the intact organism by following the rate, magnitude and architecture of global genetic changes. Such results are novel and have direct translation to human tumorigenesis and gene expression.
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