LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci
LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci
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DOI：
10.1093/genetics/iyab137
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发表时间：
2021-09-07
期刊：
影响因子：
3.3
通讯作者：
Henry, Isabelle M.
中科院分区：
文献类型：
--
作者：
Comai, Luca;Amundson, Kirk R.;Henry, Isabelle M.
大规模的结构变异，例如染色体易位，可能对适应性和表型产生深远的影响，但很难识别和表征。在这里，我们描述了一种简单而有效的方法，旨在仅使用参考基因组上映射的序列读取的剂量来识别易位。我们根据测序覆盖率对基因组片段的读数进行分箱，并识别群体中拷贝数分离的情况。对于每个剂量多态性 1Mb bin，我们测试了与其他变量 bin 的独立性，即有效的明显连锁不平衡 (LD)。在九个马铃薯（Solanum tuberosum）二单倍体家族中，影响着丝粒周围区域的易位很常见，其中两例是由于基因组错误组装造成的。在两个人群中，我们发现了影响常色臂易位的证据。在简历中。 PI 310467，7 号和 8 号染色体之间的非相互易位导致 5-3 拷贝数变化，影响各自染色体尖端的数个 Mb。在简历中。 “Alca Tarma”，chr 的终端臂。 4 易位到 chr 的尖端。 1. 使用基于寡核苷酸的荧光原位杂交绘画探针（oligo-FISH），我们测试并证实了 PI 310467 中预测的排列。在 192 个拟南芥天然种质中，剂量单倍型倾向于连续变化并导致较高的噪声，而着丝粒周围区域之间的表观 LD 表明重复的影响。这种方法（LD-CNV）应该对怀疑易位的物种有用，因为它无需基因分型即可测试连锁。
Large-scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1Mb bin, we tested independence, effectively an apparent linkage disequilibrium (LD), with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a nonreciprocal translocation between chromosomes (chr.) 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. "Alca Tarma," the terminal arm of chr. 4 translocated to the tip of chr. 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, while apparent LD between pericentromeric regions suggested the effect of repeats. This method, LD-CNV, should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.