Towards a comprehensive structural variation map of an individual human genome
Towards a comprehensive structural variation map of an individual human genome
复制标题
DOI：
10.1186/gb-2010-11-5-r52
复制
发表时间：
2010-01-01
期刊：
影响因子：
12.3
通讯作者：
Scherer, Stephen W.
中科院分区：
文献类型：
--
作者：
Pang, Andy W.;MacDonald, Jeffrey R.;Scherer, Stephen W.
背景：现在已经对几个基因组进行了测序，并对数百万个遗传变异进行了注释。虽然在绘制单核苷酸多态性（snp）和小（< 10 bp）插入/缺失（indel）图谱方面取得了重大进展，但对较大结构变异的标注还不够全面。目前还不清楚典型基因组与参考序列的差异程度，迄今为止测序的基因组分析显示拷贝数变异（CNV）和反转的结果各不相同。结果：我们将现有全基因组序列数据的计算再分析与基于微阵列的新型分析相结合，检测到12178个结构变异，覆盖40.6 Mb，这些变异在首次发表的个人基因组初始测序中没有报道。我们估计在单个基因组中总非snp变异含量为48.8 Mb。我们的研究结果表明，当考虑索引/CNVs时，该基因组与共识参考序列的差异约为1.2%，snp差异约为0.1%，反转差异约为0.3%。这些结构变异影响了4867个基因，其中约24%的结构变异不能通过snp关联推算。结论：我们的研究结果表明，迄今为止，在已发表的个体基因组中，大量的结构变异尚未报道。结构变异的显著程度和复杂性，以及对其医学相关性的日益认识，需要在个人基因组的健康相关分析中积极研究它们。该基因组结构变异的新目录为未来的比较研究提供了重要的资源。
Background: Several genomes have now been sequenced, with millions of genetic variants annotated. While significant progress has been made in mapping single nucleotide polymorphisms (SNPs) and small (< 10 bp) insertion/deletions (indels), the annotation of larger structural variants has been less comprehensive. It is still unclear to what extent a typical genome differs from the reference assembly, and the analysis of the genomes sequenced to date have shown varying results for copy number variation (CNV) and inversions.Results: We have combined computational re-analysis of existing whole genome sequence data with novel microarray-based analysis, and detect 12,178 structural variants covering 40.6 Mb that were not reported in the initial sequencing of the first published personal genome. We estimate a total non-SNP variation content of 48.8 Mb in a single genome. Our results indicate that this genome differs from the consensus reference sequence by approximately 1.2% when considering indels/CNVs, 0.1% by SNPs and approximately 0.3% by inversions. The structural variants impact 4,867 genes, and >24% of structural variants would not be imputed by SNP-association.Conclusions: Our results indicate that a large number of structural variants have been unreported in the individual genomes published to date. This significant extent and complexity of structural variants, as well as the growing recognition of their medical relevance, necessitate they be actively studied in health-related analyses of personal genomes. The new catalogue of structural variants generated for this genome provides a crucial resource for future comparison studies.