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多亲本群体中基因组祖先起源的通用建模框架。

A general modeling framework for genome ancestral origins in multiparental populations.

作者信息

Zheng Chaozhi, P Boer Martin, van Eeuwijk Fred A

机构信息

Biometris, Wageningen University and Research Centre, 6700AC Wageningen, The Netherlands

Biometris, Wageningen University and Research Centre, 6700AC Wageningen, The Netherlands.

出版信息

Genetics. 2014 Sep;198(1):87-101. doi: 10.1534/genetics.114.163006.

Abstract

The next generation of QTL (quantitative trait loci) mapping populations have been designed with multiple founders, where one to a number of generations of intercrossing are introduced prior to the inbreeding phase to increase accumulated recombinations and thus mapping resolution. Examples of such populations are Collaborative Cross (CC) in mice and Multiparent Advanced Generation Inter-Cross (MAGIC) lines in Arabidopsis. The genomes of the produced inbred lines are fine-grained random mosaics of the founder genomes. In this article, we present a novel framework for modeling ancestral origin processes along two homologous autosomal chromosomes from mapping populations, which is a major component in the reconstruction of the ancestral origins of each line for QTL mapping. We construct a general continuous time Markov model for ancestral origin processes, where the rate matrix is deduced from the expected densities of various types of junctions (recombination breakpoints). The model can be applied to monoecious populations with or without self-fertilizations and to dioecious populations with two separate sexes. The analytic expressions for map expansions and expected junction densities are obtained for mapping populations that have stage-wise constant mating schemes, such as CC and MAGIC. Our studies on the breeding design of MAGIC populations show that the intercross mating schemes do not matter much for large population size and that the overall expected junction density, and thus map resolution, are approximately proportional to the inverse of the number of founders.

摘要

下一代数量性状基因座(QTL)定位群体是由多个亲本设计而成的,在近交阶段之前引入一代到数代的杂交,以增加累积重组,从而提高定位分辨率。这类群体的例子有小鼠中的协作杂交(CC)群体和拟南芥中的多亲本高级世代杂交(MAGIC)品系。所产生的近交系的基因组是创始者基因组的细粒度随机镶嵌体。在本文中,我们提出了一个新的框架,用于对来自定位群体的两条同源常染色体上的祖先起源过程进行建模,这是QTL定位中重建每个品系祖先起源的一个主要组成部分。我们为祖先起源过程构建了一个一般的连续时间马尔可夫模型,其中速率矩阵是从各种类型的连接点(重组断点)的预期密度推导出来的。该模型可应用于有或没有自交的雌雄同株群体以及有两种不同性别的雌雄异株群体。对于具有阶段恒定交配方案的定位群体,如CC和MAGIC群体,获得了图谱扩展和预期连接点密度的解析表达式。我们对MAGIC群体育种设计的研究表明,对于大群体规模,杂交交配方案影响不大,总体预期连接点密度以及图谱分辨率大约与创始者数量的倒数成正比。

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本文引用的文献

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Haplotype probabilities in advanced intercross populations.单倍型概率在高级互交群体中。
G3 (Bethesda). 2012 Feb;2(2):199-202. doi: 10.1534/g3.111.001818. Epub 2012 Feb 1.
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Distribution of parental genome blocks in recombinant inbred lines.重组近交系中亲本基因组块的分布。
Genetics. 2011 Oct;189(2):645-54. doi: 10.1534/genetics.111.129700. Epub 2011 Aug 11.
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Genetics. 2008 Jun;179(2):1069-78. doi: 10.1534/genetics.107.083873. Epub 2008 May 27.

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