Abernathy J, Li X, Jia X, Chou W, Lamont S J, Crooijmans R, Zhou H
Department of Animal Science, University of California, Davis, CA, 95616, USA.
Anim Genet. 2014 Jun;45(3):400-11. doi: 10.1111/age.12141. Epub 2014 Mar 15.
Copy number variation refers to regions along chromosomes that harbor a type of structural variation, such as duplications or deletions. Copy number variants (CNVs) play a role in many important traits as well as in genetic diversity. Previous analyses of chickens using array comparative genomic hybridizations or single-nucleotide polymorphism chip assays have been performed on various breeds and genetic lines to discover CNVs. In this study, we assessed individuals from two highly inbred (inbreeding coefficiency > 99.99%) lines, Leghorn G-B2 and Fayoumi M15.2, to discover novel CNVs in chickens. These lines have been previously studied for disease resistance, and to our knowledge, this represents the first global assessment of CNVs in the Fayoumi breed. Genomic DNA from individuals was examined using the Agilent chicken 244 K comparative genomic hybridization array and quantitative PCR. We identified a total of 273 CNVs overall, with 112 CNVs being novel and not previously reported. Quantitative PCR using the standard curve method validated a subset of our array data. Through enrichment analysis of genes within CNV regions, we observed multiple chromosomes, terms and pathways that were significantly enriched, largely dealing with the major histocompatibility complex and immune responsiveness. Using an additional round of computational and statistical analysis with a different bioinformatic pipeline, we identified 43 CNVs among these as high-confidence regions, 14 of which were found to be novel. We further compared and contrasted individuals of the two inbred lines to discover regions that have a significant difference in copy number between lines. A total of 40 regions had significant deletions or duplications between the lines. Gene Ontology analysis of genomic regions containing CNVs between lines also was performed. This between-line candidate CNV list will be useful in studies with these two unique genetic lines, which may harbor variations that underlie quantitative trait loci for disease resistance and other important traits. Through the global discovery of novel CNVs in chicken, these data also provide resources for further genetic and functional genomics studies.
拷贝数变异是指染色体上存在的一类结构变异区域，如重复或缺失。拷贝数变异（CNV）在许多重要性状以及遗传多样性中发挥作用。此前利用阵列比较基因组杂交或单核苷酸多态性芯片分析对鸡进行的研究，已在多个品种和遗传系中开展，以发现CNV。在本研究中，我们评估了两个高度近交（近交系数>99.99%）品系，即来航鸡G - B2和法尤米鸡M15.2的个体，以发现鸡中的新CNV。这些品系此前已针对抗病性进行过研究，据我们所知，这是对法尤米品种CNV的首次全面评估。使用安捷伦鸡244K比较基因组杂交阵列和定量PCR对个体的基因组DNA进行检测。我们总共鉴定出273个CNV，其中112个是新的且此前未被报道过。使用标准曲线法的定量PCR验证了我们阵列数据的一个子集。通过对CNV区域内基因的富集分析，我们观察到多个染色体、术语和通路显著富集，主要涉及主要组织相容性复合体和免疫反应性。使用不同的生物信息学流程进行另一轮计算和统计分析，我们在这些区域中鉴定出43个CNV为高置信度区域，其中14个被发现是新的。我们进一步比较了这两个近交系的个体，以发现品系间拷贝数存在显著差异的区域。品系间共有40个区域存在显著的缺失或重复。还对品系间含有CNV的基因组区域进行了基因本体分析。这个品系间候选CNV列表将有助于对这两个独特遗传系的研究，它们可能含有对抗病性和其他重要性状的数量性状位点起基础作用的变异。通过在鸡中全面发现新的CNV，这些数据也为进一步的遗传和功能基因组学研究提供了资源。
