Genetic divergence and the genetic architecture of complex traits in chromosome substitution strains of mice.
Genetic divergence and the genetic architecture of complex traits in chromosome substitution strains of mice.
复制标题
DOI：
10.1186/1471-2156-13-38
复制
发表时间：
2012-05-18
期刊：
影响因子：
2.9
通讯作者：
Nadeau JH
中科院分区：
文献类型：
--
作者：
Spiezio SH;Takada T;Shiroishi T;Nadeau JH
复杂性状的遗传结构强烈影响遗传突变、基因工程、环境和遗传扰动以及自然选择和人工选择的后果。但由于大多数研究的动力不足，复杂特征的图景往往是不完整的。染色体替代菌株(CSS)是这些基因组调查的独特范例，因为它们能够在统一的近亲繁殖遗传背景上对每条染色体的表型效应进行统计上独立的、强大的测试。先前在小鼠和大鼠中进行的CSS调查揭示了许多复杂的性状基因(QTL)、大的表型效应、广泛的上位性，以及系统特性，如强烈的方向性表型变化和遗传决定的表型变异范围的限制。然而，在该研究中，CS前体菌株之间异常密切的遗传关系提出了关于遗传差异的影响的问题：随着基因调控和蛋白质功能的相应变化，前体菌株之间的更大差异是否会导致显著更独特的表型特征，或者上位性和系统限制，这些在CSS中普遍存在，无论DNA序列变异的程度如何，是否会限制表型变异的范围？我们对两个新的CSS小组的性状进行了广泛的调查，其中供体菌株来自起源较远的近交系菌株，我们分析了结果，发现三个CS小组在遗传和系统属性上非常相似，而不考虑分歧时间。我们的结果认为，宿主菌株和供体菌株之间的DNA序列差异并没有实质性地影响复杂性状的结构，相反，强烈的上位性缓冲了遗传差异的表型效应，从而限制了表型变异的范围。
The genetic architecture of complex traits strongly influences the consequences of inherited mutations, genetic engineering, environmental and genetic perturbations, and natural and artificial selection. But because most studies are under-powered, the picture of complex traits is often incomplete. Chromosome substitution strains (CSSs) are a unique paradigm for these genome surveys because they enable statistically independent, powerful tests for the phenotypic effects of each chromosome on a uniform inbred genetic background. A previous CSS survey in mice and rats revealed many complex trait genes (QTLs), large phenotypic effects, extensive epistasis, as well as systems properties such as strongly directional phenotypic changes and genetically-determined limits on the range of phenotypic variation. However, the unusually close genetic relation between the CSS progenitor strains in that study raised questions about the impact of genetic divergence: would greater divergence between progenitor strains, with the corresponding changes in gene regulation and protein function, lead to significantly more distinctive phenotypic features, or alternatively would epistasis and systems constraints, which are pervasive in CSSs, limit the range of phenotypic variation regardless of the extent of DNA sequence variation? We analyzed results for an extensive survey of traits in two new panels of CSSs where the donor strains were derived from inbred strains with more distant origins and discovered a strong similarity in genetic and systems properties among the three CSS panels, regardless of divergence time. Our results argue that DNA sequence differences between host and donor strains did not substantially affect the architecture of complex traits, and suggest instead that strong epistasis buffered the phenotypic effects of genetic divergence, thereby constraining the range of phenotypic variation.
登录
查看更多内容
影响因子：
56.9
作者：
Singer, JB;Hill, AE;Nadeau, JH
通讯作者：
Nadeau, JH
DOI：
10.1073/pnas.0810388105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Shao, Haifeng;Burrage, Lindsay C.;Nadeau, Joseph H.
通讯作者：
Nadeau, Joseph H.
影响因子：
2.1
作者：
Fox, CW;Czesak, ME;Wallin, WG
通讯作者：
Wallin, WG
影响因子：
5.4
作者：
Saha, S.;Wu, J.;Stelly, D. M.
通讯作者：
Stelly, D. M.
影响因子：
4.9
作者：
Geraldes A;Basset P;Smith KL;Nachman MW
通讯作者：
Nachman MW