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设计一个在已实现的协作杂交遗传参考群体中实施的数量性状基因座定位研究。

Designing a QTL Mapping Study for Implementation in the Realized Collaborative Cross Genetic Reference Population.

作者信息

Soller Morris, Abu-Toamih Atamni Hanifa J, Binenbaum Ilona, Chatziioannou Aristotelis, Iraqi Fuad A

机构信息

Department of Genetics, Silverman Institute for Life Sciences, Hebrew University, Jerusalem, Israel.

Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.

出版信息

Curr Protoc Mouse Biol. 2019 Dec;9(4):e66. doi: 10.1002/cpmo.66.

DOI:10.1002/cpmo.66
PMID:31756057
Abstract

The Collaborative Cross (CC) mouse resource is a next-generation mouse genetic reference population (GRP) designed for high-resolution mapping of quantitative trait loci (QTL) of large effect affecting complex traits during health and disease. The CC resource consists of a set of 72 recombinant inbred lines (RILs) generated by reciprocal crossing of five classical and three wild-derived mouse founder strains. Complex traits are controlled by variations within multiple genes and environmental factors, and their mutual interactions. These traits are observed at multiple levels of the animals' systems, including metabolism, body weight, immune profile, and susceptibility or resistance to the development and progress of infectious or chronic diseases. Herein, we present general guidelines for design of QTL mapping experiments using the CC resource-along with full step-by-step protocols and methods that were implemented in our lab for the phenotypic and genotypic characterization of the different CC lines-for mapping the genes underlying host response to infectious and chronic diseases. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: CC lines for whole body mass index (BMI) Basic Protocol 2: A detailed assessment of the power to detect effect sizes based on the number of lines used, and the number of replicates per line Basic Protocol 3: Obtaining power for QTL with given target effect by interpolating in Table 1 of Keele et al. (2019).

摘要

协作杂交(CC)小鼠资源是一种新一代小鼠遗传参考群体(GRP),旨在对影响健康和疾病期间复杂性状的大效应数量性状基因座(QTL)进行高分辨率定位。CC资源由一组72个重组近交系(RIL)组成,这些重组近交系是通过五个经典和三个野生来源的小鼠奠基菌株的相互杂交产生的。复杂性状受多个基因内的变异、环境因素及其相互作用的控制。这些性状在动物系统的多个层面上都能观察到,包括新陈代谢、体重、免疫特征以及对传染病或慢性病发展和进程的易感性或抵抗力。在此,我们提出了使用CC资源进行QTL定位实验设计的一般指南,以及我们实验室为不同CC系的表型和基因型特征鉴定所实施的完整的逐步方案和方法,用于定位宿主对传染病和慢性病反应的潜在基因。© 2019 John Wiley & Sons, Inc. 基本方案1:用于全身体重指数(BMI)的CC系 基本方案2:基于所用品系数量和每个品系的重复次数对检测效应大小的能力进行详细评估 基本方案3:通过在Keele等人(2019年)的表1中进行插值获得具有给定目标效应的QTL的功效

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