Recent, full-length gene retrocopies are common in canids.
Recent, full-length gene retrocopies are common in canids.
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DOI：
10.1101/gr.276828.122
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发表时间：
2022-08-25
期刊：
影响因子：
7
通讯作者：
Bannasch, Danika
中科院分区：
文献类型：
--
作者：
Batcher, Kevin;Varney, Scarlett;York, Daniel;Blacksmith, Matthew;Kidd, Jeffrey M;Rebhun, Robert;Dickinson, Peter;Bannasch, Danika
基因逆转录是由经过处理的mRNA转录物的反转录和插入基因组而产生的。尽管许多逆转录体获得了突变，使它们在功能上失去活性，但大多数哺乳动物保留了能够产生新的逆转录体的活性LINE-1序列。新的逆转录，称为逆转录拷贝数变异（retroCNVs），在高通量测序数据中可能无法通过标准变异调用技术识别。尽管多种功能性FGF4逆转录cnvs与狗的骨骼发育不良有关，但犬类逆转录cnvs的全部情况尚未被表征。在这里，对来自76个品种的293只狗的全基因组测序数据集进行了retroCNV发现。我们通过mrna特异性30-mers的存在鉴定了retroCNV亲本基因，然后通过不一致读取分析鉴定了retroCNV插入位点。我们总共解析了来自1179个亲本基因的1911个retrocnv的插入位点，其中1236个看起来与亲本基因相同。狗平均有54.1个总逆转录cnvs和1.4个私有逆转录cnvs。我们在6只金毛寻回犬中发现了12%（14/113）的逆转录cnvs在睾丸中表达的证据，其中包括4个嵌合转录物，并且97个逆转录cnvs在犬种之间的FST也显著升高，可能表明选择。我们将我们的方法应用于人类基因组的一个子集，每个样本平均检测到4.2个retroCNV，突出显示狗的retroCNV频率相对增加了13倍。特别是在犬科动物中，逆转录cnvs是一个很大程度上未被探索的遗传变异来源，它可以促进基因组可塑性，在研究性状和疾病时应该考虑到这一点。
Gene retrocopies arise from the reverse transcription and insertion into the genome of processed mRNA transcripts. Although many retrocopies have acquired mutations that render them functionally inactive, most mammals retain active LINE-1 sequences capable of producing new retrocopies. New retrocopies, referred to as retro copy number variants (retroCNVs), may not be identified by standard variant calling techniques in high-throughput sequencing data. Although multiple functional FGF4 retroCNVs have been associated with skeletal dysplasias in dogs, the full landscape of canid retroCNVs has not been characterized. Here, retroCNV discovery was performed on a whole-genome sequencing data set of 293 canids from 76 breeds. We identified retroCNV parent genes via the presence of mRNA-specific 30-mers, and then identified retroCNV insertion sites through discordant read analysis. In total, we resolved insertion sites for 1911 retroCNVs from 1179 parent genes, 1236 of which appeared identical to their parent genes. Dogs had on average 54.1 total retroCNVs and 1.4 private retroCNVs. We found evidence of expression in testes for 12% (14/113) of the retroCNVs identified in six Golden Retrievers, including four chimeric transcripts, and 97 retroCNVs also had significantly elevated FST across dog breeds, possibly indicating selection. We applied our approach to a subset of human genomes and detected an average of 4.2 retroCNVs per sample, highlighting a 13-fold relative increase of retroCNV frequency in dogs. Particularly in canids, retroCNVs are a largely unexplored source of genetic variation that can contribute to genome plasticity and that should be considered when investigating traits and diseases.