De novo assembly of a haplotype-resolved human genome
De novo assembly of a haplotype-resolved human genome
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DOI：
10.1038/nbt.3200
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发表时间：
2015-06-01
影响因子：
46.9
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Cao, Hongzhi;Wu, Honglong;Wang, Jun
人类基因组是二倍体，了解每条染色体上的变异对于解释基因组信息非常重要。在这里，我们报道了不使用参考基因组组装单倍体-解决二倍体基因组。我们的产品线依赖于fosmid池和全基因组霰弹枪策略，完全基于下一代测序和分层组装方法。我们将我们的测序方法应用于一个亚洲个体的基因组，得到了一个5.15 gb的组装基因组，单倍型N50为484kb。我们的分析发现了以前未检测到的索引和7.49 Mb的新编码序列，这些序列不能与人类参考基因组对齐，其中包括至少6个预测基因。这个单倍型分解基因组代表了迄今为止最完整的人类基因组组装。应用我们的方法来识别个体单倍型差异应该有助于将基因型转化为表型，以促进个性化医疗的发展。
The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.