A Collaborative Cross for High-Precision Complex Trait Analysis CTC Workgroup Report
A Collaborative Cross for High-Precision Complex Trait Analysis CTC Workgroup Report
复制标题
高精度复杂性状分析的协作交叉 CTC 工作组报告
DOI：
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
D. Threadgill
中科院分区：
文献类型：
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作者：
Robert W. Williams;K. Broman;J. Cheverud;G. Churchill;Robert Hitzemann;K. Hunter;J. Mountz;D. Pomp;R. Reeves;L. Schalkwyk;D. Threadgill
The goal of the Complex Trait Consortium (CTC) is to produce greatly improved resources that can be used to understand, treat, and ultimately prevent the most pervasive human diseases. Essentially all 20 human diseases are complex in the sense that incidence, severity, and outcome are determined by interactions among many genes and environmental factors. Cancer, diabetes, heart and lung disease, Alzheimer’s, and infectious diseases all fall into this category. Members of the CTC have spent the past year devising a detailed plan to generate a single collaborative genetic resource that will greatly accelerate the study of human disease. The resource is called the Collaborative Cross. This Report explains our reasoning and provides an outline of the methods and costs associated with making the Collaborative Cross. 30 Introduction to the Collaborative Cross Eleven members of the Complex Trait Consortium (CTC) met at Johns Hopkins University, August 30, 2002, to refine ideas that were initially proposed at CTC meetings in Edinburgh (Nov 2001) and Memphis (May 2002). We focused on how to move forward on a large-scale collaborative project to provide biomedical researchers with much more powerful resources for 10 systematic analysis of complex traits. We plan to submit proposals to support the Collaborative Cross in the USA, Europe (Leo Schalkwyk and colleagues), and Australia (Grant Morahan and colleagues) in 2003. At least seven years of funding will be required to meet initial goals. A summary of work that led to the meeting at Johns Hopkins is provided in a recent paper by Threadgill and colleagues (2002). Additional papers, abstracts, and pdf files (including this report) are available online at www.complextrait.org. Gibson and Mackay (2002) have summarized work to produce 20 more powerful community resources for evolutionary genomics that in many ways parallel and complement our CTC efforts. The Baltimore workgroup explored alternative methods to produce a large multipurpose set of recombinant inbred (RI) strains of mice. We settled on a cross that will combine eight inbred strains and that will therefore be useful for the analysis of virtually any murine complex trait. The plan summarized in this report is still provisional, and we solicit your input and criticism. The selection of strains is particularly critical, and this open topic is considered in more detail below. We have 30 opted to select strains that provide the greatest genetic diversity. In all likelihood, some preference will be given to several strains that are widely used by the community. www.complextrait.org CTC Workshop Report While the workshop dealt specifically with our proposal to generate a large set of RI strains, many CTC members are actively developing complementary methods to study complex traits. The Collaborative Cross is not intended to supplant other work or the development of other resources. However, the consensus of the CTC is that this particular project should have highest priority. This report is divided into three parts. The first part summarizes aims of the resource aims and answers the question: What will the RI cross accomplish in terms of precision and power, and 10 how will it be used by the biomedical research community? The second part summarizes a specific implementation of the Collaborative Cross. This section incorporates initial results of simulations and calculations concerning our recommended implementation. The third part is an outline of how a large CTC effort leading to the Collaborative Cross can be structured and distributed across a diverse and international community of researchers using mice in a wide variety of research projects. PART I. AIMS AND REQUIREMENTS In this section we briefly review nine aims that were 20 considered in designing a single integrated collaborative cross for complex trait analysis.
