Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Semex, 5653 HWY6 North, Guelph, ON, Canada.
Sci Rep. 2017 May 9;7(1):1631. doi: 10.1038/s41598-017-01793-2.
We have identified de novo copy number variations (CNVs) generated in bulls as they age. Blood samples from eight bulls were collected and SNP arrayed in a prospective design over 30 months allowing us to differentiate de novo CNVs from constant CNVs that are present throughout the sampling period. Quite remarkably, the total number of CNVs doubled over the 30-month period, as we observed an almost equal number of de novo and constant CNVs (107 and 111, respectively, i.e. 49% and 51%). Twice as many de novo CNVs emerged during the second half of the sampling schedule as in the first part. It suggests a dynamic generation of de novo CNVs in the bovine genome that becomes more frequent as the age of the animal progresses. In a second experiment de novo CNVs were detected through in vitro ageing of bovine fibroblasts by sampling passage #5, #15 and #25. De novo CNVs also became more frequent, but the proportion of them was only ~25% of the total number of CNVs (21 out of 85). Temporal generation of de novo CNVs resulted in increasing genome coverage. Genes and quantitative trait loci overlapping de novo CNVs were further investigated for ageing related functions.
我们已经鉴定了随着公牛年龄增长而产生的新生拷贝数变异（CNV）。在 30 个月的前瞻性设计中，从 8 头公牛收集血液样本并进行 SNP 排列，使我们能够区分在整个采样期间存在的新生 CNV 和恒定 CNV。非常显著的是，在 30 个月的时间里，CNV 的总数增加了一倍，因为我们观察到新生 CNV 和恒定 CNV 的数量几乎相等（分别为 107 个和 111 个，即 49%和 51%）。在采样计划的后半段，新生 CNV 的出现数量是前半段的两倍。这表明在牛基因组中存在动态的新生 CNV 生成，随着动物年龄的增长，这种生成变得更加频繁。在第二个实验中，通过对牛成纤维细胞进行体外老化（取样传代#5、#15 和#25）来检测新生 CNV。新生 CNV 也变得更加频繁，但它们仅占 CNV 总数的~25%（85 个中的 21 个）。新生 CNV 的时间生成导致基因组覆盖范围增加。基因和数量性状基因座与新生 CNV 重叠的基因进一步研究了与衰老相关的功能。
