Gheyas Almas A, Boschiero Clarissa, Eory Lel, Ralph Hannah, Kuo Richard, Woolliams John A, Burt David W
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
DNA Res. 2015 Jun;22(3):205-17. doi: 10.1093/dnares/dsv005. Epub 2015 Apr 29.
Next-generation sequencing has prompted a surge of discovery of millions of genetic variants from vertebrate genomes. Besides applications in genetic association and linkage studies, a fraction of these variants will have functional consequences. This study describes detection and characterization of 15 million SNPs from chicken genome with the goal to predict variants with potential functional implications (pfVars) from both coding and non-coding regions. The study reports: 183K amino acid-altering SNPs of which 48% predicted as evolutionary intolerant, 13K splicing variants, 51K likely to alter RNA secondary structures, 500K within most conserved elements and 3K from non-coding RNAs. Regions of local fixation within commercial broiler and layer lines were investigated as potential selective sweeps using genome-wide SNP data. Relationships with phenotypes, if any, of the pfVars were explored by overlaying the sweep regions with known QTLs. Based on this, the candidate genes and/or causal mutations for a number of important traits are discussed. Although the fixed variants within sweep regions were enriched with non-coding SNPs, some non-synonymous-intolerant mutations reached fixation, suggesting their possible adaptive advantage. The results presented in this study are expected to have important implications for future genomic research to identify candidate causal mutations and in poultry breeding.
新一代测序技术促使从脊椎动物基因组中发现了数以百万计的遗传变异。除了应用于基因关联和连锁研究外，这些变异中的一部分将产生功能影响。本研究描述了从鸡基因组中检测和鉴定1500万个单核苷酸多态性（SNP），目的是预测编码区和非编码区具有潜在功能影响的变异（pfVars）。该研究报告如下：18.3万个改变氨基酸的SNP，其中48%被预测为进化上不耐受；1.3万个剪接变异；5.1万个可能改变RNA二级结构；50万个位于最保守元件内；3000个来自非编码RNA。利用全基因组SNP数据，研究了商业肉鸡和蛋鸡品系中的局部固定区域，将其作为潜在的选择性清除区域。通过将清除区域与已知的数量性状基因座（QTL）重叠，探索了pfVars与表型（如有的话）之间的关系。基于此，讨论了一些重要性状的候选基因和/或因果突变。虽然清除区域内的固定变异富含非编码SNP，但一些非同义不耐受突变达到了固定状态，表明它们可能具有适应性优势。本研究结果有望对未来鉴定候选因果突变的基因组研究以及家禽育种产生重要影响。
