Enhanced Development of the Xiphophorus Model System

描述（申请人提供）：剑鱼作为基础生物医学研究的实验模型已有75年以上的历史。最终，“机械性”假说必须用完整的动物模型系统来证实。具有良好特征的各种实验动物模型最适合提供这一功能。在我们未来的科学环境中，多样化的动物模型使我们能够更好地理解复杂的可遗传（多基因）特征，这对于我们试图解开复杂特征（如行为和导致生活史替代的成分）背后的遗传学至关重要。本R24提案旨在维护和加强剑鱼遗传资源中心（XGSC）。自20世纪30年代以来，XGSC一直在美国境内运作。xiphohorus模型的传统优势包括对完整动物中与复杂（多遗传）表型相关的遗传模式进行无偏见评估。剑鱼种间（已知26个分类群）的极端遗传变异和产生可育的种间杂种的能力，使得个体回交杂交后代能够遵循染色体/标记遗传。在一个队列中涉及数百只动物的统计分析可以用来识别与任何感兴趣的性状相关的标记，只要表型（作为单一性状或QTL）可以在两个亲本系/物种之间和杂交后代中辨别出来。这个实验系统在检验从全动物基因组分析中产生的假设方面越来越有用（见附39封以上支持XGSC的信函）。考虑到这些期望，我们有理由继续向研究实验室提供剑鱼的血统和相关材料，继续我们在开发冷冻保存程序方面的进展，以确保库存的长期可用性，并进一步开发当代基因组工具，供研究科学家使用和/或预期使用这种有价值的脊椎动物实验模型。因此，我们的具体目标是：(1)保护和加强剑鱼遗传资源中心，并根据每位研究者的要求，为研究界提供来自遗传管理系的动物和材料。(2)建立广泛的EST（表达序列标签）标记数据库。EST标记注释和数据库将提供给社区。(3)将前期项目开发的xiphohorus重组基因图谱与目前正在构建的BAC最小平铺路径（BAC- mtp）物理图谱进行比对。(4)继续发展冷冻保存剑鱼精子样本的技术，并提供一项保存计划，将剑鱼鱼线作为冷冻保存标本进行保存，以保护其遗传遗产。

DESCRIPTION (provided by applicant): Xiphophorus fishes have been used as an experimental model for fundamental biomedical research for over 75 years. Eventually "mechanistic" hypothesis must be confirmed using intact animal model systems. Well-characterized diverse experimental animal models are best suited to provide this function. In our future scientific environment, diverse animal models that allow us to better understand complex heritable (multigenic) traits will be of considerable importance as we attempt to unravel the genetics underlying complex traits such as behavior and the components leading to alternative in life histories. This R24 proposal is designed to maintain and enhance the Xiphophorus Genetic Stock Center (XGSC). The XGSC has operated within the United States since the 1930's. The traditional strength of the Xiphophorus model involves the non-biased assessment of genetic inheritance patterns associated with complex (multi-genetic) phenotypes within intact animals. The extreme genetic variability among Xiphophorus species (26 known taxa) and capability of producing fertile interspecies hybrids allows chromosomal/marker inheritance to be followed in individual backcross hybrid progeny. Statistical analyses involving hundreds of animals in a cohort can be used to identify markers linked to any trait of interest, so long as the phenotype (as a singular trait or QTL) can be discerned between two parental lines/species and in hybrid progeny. This experimental system is increasingly useful to test hypotheses generated from analyses of whole animal genomes (see 39+ letters of support for the XGSC, appended). With these expectations in mind, it is reasonable to continue to provide pedigreed Xiphophorus fish and associated materials to research laboratories, to continue our progress in development of cryopreservation procedures to ensure long term availability of stocks, and to further develop contemporary genomic tools for research scientists using and/or anticipating use of this valuable vertebrate experimental model. Accordingly our specific aims are: (1) To preserve and enhance the Xiphophorus Genetic Stock Center and provide the research community with animals and materials from genetically managed lines according to the specifications of each investigator. (2) To develop an extensive database of expressed sequence tag (EST) markers. EST marker annotation and the databases will be made available to the community. (3) We will collate the Xiphophorus recombination gene map developed in the previous project period with the BAC minimal tiling path (BAC-MTP) physical map currently being constructed. (4) To continue development of technology allowing cryopreservation of Xiphophorus sperm samples and to provide a preservation program where the XGSC fish lines are maintained as cryopreserved specimens to protect their genetic heritage.