A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice

A protocol for high-throughput phenotyping, suitable for quantitative trait analysis in mice
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DOI:
10.1007/s00335-005-0112-1
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发表时间:
2006-02-01
期刊:
影响因子:
2.5
通讯作者:
Flint, J
Flint, J
中科院分区:
生物学4区
文献类型:
--
作者:
Solberg, LC;Valdar, W;Flint, J

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在远交小鼠群体中的全基因组遗传关联研究代表了一种新的方法来识别自然发生的遗传变异的分子基础,这是近交系小鼠之间数量变异的主要来源。在每只小鼠上平行测量多个表型将使该方法具有成本效益,但是还没有开发出足够大规模的表型分析方案。在这篇文章中,我们描述了一个协议的开发和部署,以收集人类疾病(焦虑,II型糖尿病和哮喘)的三种模型的措施,以及小鼠血液生化,免疫学和血液学的措施。我们报告说,该协议提供了高度显着的差异之间的8个近交系(A/J,AKR/J,BALBc/J,CBA/J,C3 H/HeJ,C57 BL/6 J,DBA/2 J,和LP/J),小鼠的遗传异质性股票(HS)的祖先。我们报告成功地收集了2000个远交HS动物的多种表型。该方案中测量的表型形成了对小鼠复杂性状遗传基础的大规模调查的基础,旨在研究基因之间以及基因与环境之间的相互作用,以及遗传变异对表型的主要影响。
Whole-genome genetic association studies in outbred mouse populations represent a novel approach to identifying the molecular basis of naturally occurring genetic variants, the major source of quantitative variation between inbred strains of mice. Measuring multiple phenotypes in parallel on each mouse would make the approach cost effective, but protocols for phenotyping on a large enough scale have not been developed. In this article we describe the development and deployment of a protocol to collect measures on three models of human disease (anxiety, type II diabetes, and asthma) as well as measures of mouse blood biochemistry, immunology, and hematology. We report that the protocol delivers highly significant differences among the eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a genetically heterogeneous stock (HS) of mice. We report the successful collection of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in the protocol form the basis of a large-scale investigation into the genetic basis of complex traits in mice designed to examine interactions between genes and between genes and environment, as well as the main effects of genetic variants on phenotypes.