解析鸡27号染色体影响生长性状的致因突变及功能基因

Growth traits of broilers have significant economic value in chicken industry. To resolve the genetic basis of complex traits is the keystone and difficulty of research in poultry genetic breeding. Many studies have confirmed that there was a major effect QTL affecting shank length and body weight at the intermediate section of chicken chromosome 27, but there is still no consensus as to the underlying genetic mechanism. In our previous research, the QTL on chromosome 27 was reconfirmed using a fourteen-generation chicken advanced intercross population (AIL) and zoom out to a 150 Kb interval by F9 genome-wide association study, which sheltered several functional genes involving skeletal development and intestinal digestion and metabolism. Here, this locus will be dissected in detail using F9 and F14 samples. A series of progressive analyses including single/haplotype association analysis in F9, IBD (Identity-by-descent) mapping from F0 to F9 and haplotype sharing analysis in 11 other breeds, RNA-seq and ATAC-seq will be employed to fine-mapping this QTL region. This study aims to decipher the causal mutation and functional gene for growth traits in this QTL by integrating the results of genetic mapping and transcriptional regulation. It will be a valuable example of the genomic complexity to be expected in studies of the genetic architecture of quantitative traits in segregating populations via a series of innovative methods and genetic materials. Meanwhile, this study will provide new perspectives for the next generation of poultry genetic breeding.

鸡生长性状遗传机制的解析可带来巨大经济效益，是家禽遗传育种的重难点所在。多个研究组已发现鸡27号染色体中部的QTL可显著影响鸡胫长、体重等重要生长性状，但具体的致因突变和致因基因尚不明确。本研究前期构建了14代的鸡深度杂交系，在家系F9代进行全基因组关联分析，将QTL候选区间缩小至150Kb，该区间包含多个明确影响骨骼发育、肠道消化代谢的功能基因。本课题将以上述结果为基础，利用F9和F14代样本展开进一步精细定位，结合基因组单点/单倍型关联分析，IBD定位，比较基因组分析，RNA-seq，ATAC-seq等技术手段，整合遗传定位和转录调控两个层级的研究结果，解析该QTL影响鸡生长性状的致因突变和功能基因。本研究以定位该区域主效基因并解析其调控机制为明确目标，整合多组学数据和一系列创新方法及遗传素材，期望通过对遗传机制的解析，取得动物遗传研究突破性进展，为家禽遗传育种改良提供创新理论指导。

鸡生长性状遗传机制的解析可带来巨大经济效益，是家禽遗传育种的重难点所在。为了更好地理解骨骼发育等生长性状的遗传结构，本研究构建了16代的鸡深度杂交系，通过多个代次的遗传结构评估证明该群体已经将奠基者基因组充分地随机碎片化，并具有快速连锁不平衡衰减、等位基因频率稳定和核苷酸多样性丰富等特点。在家系F9代和F16代进行了全基因组关联分析，挖掘到了1、4、27号染色体的主效QTL区间。在27号染色体的QTL上，鉴定到了PHOPHO1、IGF2BP1、ZNF652、和GIP四个基因，通过不同的调控途径影响鸡骨骼的生长。我们的研究提供了一个合理的用于检测数量性状基因和追踪祖先历史的资源，有助于我们理解鸡骨胳生长的遗传机制。进一步地，为了更好地解析调控型突变在复杂数量性状中发挥的关键作用，通过合作研究生成了鸡23个主要组织的总共377个表观基因组、转录组和染色质构象数据集，构建了23个组织的调控元素图谱，并探索了它们的组织特异性功能。通过组织特异性调节元件的富集分析进一步鉴定了与复杂性状相关的特定遗传变异。研究发现两个调控型SNP靶向成纤维细胞生长因子9 (FGF9) 基因，肠道共有增强子上的SNPs可能会影响FGF9的表达，进而影响肠道功能，如营养吸收的变化，进而影响体重、胫骨长度等生长性状。该研究证明了GWAS注释的综合分析不仅缩小了复杂性状的潜在致因突变，而且为未来的多组学整合研究奠定了基础。