通过定位选择信号和分析位点间互作解析鸡体重的遗传基础

Body weight is one of the most important breeding indexes in chicken, as well as a classical quantitative trait. Recently, the “missing heritability” has been revealed while studying its underlying genetic basis by linkage analyses and genome-wide association studies. There are two main reasons that can cause such problem, one is due to the trait’s highly polygenic nature and limited power in the experimental design that a substantial proportion of the additive loci can not be identified; the other is that the epistatic effects between/among loci tend to be overlooked. Herein, in order to understand the genetic mechanisms underlying body weight in-depth, we plan to perform the searches for body-weight associated adaptive loci and the comprehensive detection of epistatic interaction effects. Five Chinese indigenous chicken breeds will be selected as the subjects, three of which are the smallest local breeds, while the other two are the biggest. Also, red jungle fowls and cobb broiler will be included as the control groups. Our target trait is the adult body-weight. By using the whole-genome re-sequencing data and correcting for population stratification, we aim to identify adaptive loci that are associated with long-term divergent natural and artificial selection on body weight. Such results would be a significant complement to the current detection on additive genetic variants. Thereafter, based on the customized high-density SNP chip, epistatic effects between loci within the adaptive regions will be comprehensively evaluated by using exhaustive epistatic model and vGWAS method. Then, by performing bioinformatics analysis on the significant epistatic pairs, important regulatory pathways controlling body-weight can be found. Last but not least, all results will be confirmed either by statistical analysis on the other set of sample individuals or by quantitative evaluation on their expression models. This study will not only help us to comprehensively dissect the genetic basis underlying the complex body-weight trait, but also provide an important guidance while applying marker-assisted selection on chickens in the future.

体重是鸡的重要育种指标之一，为典型的数量性状；近年来利用连锁和关联分析解析其遗传基础发现存在“缺失遗传力”的现象，定位的加性遗传位点不全以及未考虑位点间互作可能是导致该现象的重要原因。本项目将结合选择信号定位以及互作效应分析深入并全面地解析鸡体重性状的主要遗传基础。拟以五个体重差异显著的地方鸡种为素材，以红色原鸡和科宝肉鸡为对照，以成年体重为目标性状，首先利用全基因组测序数据，校正品种间遗传背景差异后筛选获得与体重适应性进化相关的受选择位点，结合已知QTL补充完善与体重相关的加性遗传位点；再基于高通量基因型数据，使用两位点互作模型和vGWAS方法在上述候选区域内估计位点间的互作效应，结合生物信息学分析鉴定1-2个控制体重的重要通路；最后，利用扩群统计和表达定量等对所得结果进行重复及验证。本研究结果将有助于揭示鸡体重性状复杂的遗传结构和模式，为高效精准地进行鸡的标记辅助选择奠定重要理论基础。

体重性状是鸡良种选育的一个关键指标。同时作为一个复杂数量性状，全面解析其复杂遗传结构（包括相关遗传位点的位置、数量、以及不同品种中效应大小和方向，位点间互作和遗传与环境互作等）对于鸡高效精准育种有重要的指导意义。本项目以体重差异显著的10个地方鸡种为研究对象，一方面致力于综合利用多水平（单位点，单倍型和多性状等）的关联分析手段结合差异选择信号筛选，在有限实验群体中提高关联定位的效力和精度。研究遗传背景较简单的黄羽性状时，完善该综合分析平台后定位到了三个主效QTL。其中位于2号染色体上的主效QTL（解释约19%的表型方差）进一步地被精细定位到较小的单倍型区间，并筛选获得CHST11，DSG4，GATA6和CABLES1等与毛囊发育相关的重要功能基因；另一方面应用上述综合分析平台，不局限于检测加性遗传位点在单个群体/品种中的效应和分布，更深入地解析包括品种间遗传效应大小和方向的异同以及非加性遗传效应等影响鸡体重的机制。研究结果表明，鸡体重性状的遗传复杂性不仅仅表现在其微效多基因的遗传基础（13个QTL位点和144个差异选择位点），还体现在不同品种间主效位点有区别（4/6位点）、甚至在共同主效位点中不同品种具有迥异的遗传进化机制（9号染色体的体重QTL作为四个品种间共有位点，其在狼山鸡中进化出不同单倍型以获得对体重的遗传增效作用）。此外，遗传位点间的互作以及遗传与环境互作也对体重有不可忽视的遗传效应。在遗传选育逐步逼近鸡生理极限，且多元化养殖模式蓬勃发展的今天，全面评估复杂重要经济性状（如体重）的遗传结构，有助于更高效精准地推动育种进展，实现多样化的育种目标。