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Novel Sequence Discovery by Subtractive Genomics
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来自丹麦的150个基因组的测序和de novo组装作为人口参考
Lasse Maretty1, Jacob Malte Jensen2,3, Bent Petersen4
1Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
Nature
|July 27, 2017
概括
高覆盖度测序使得优秀的新基因组组合成为可能,揭示了广泛的结构变异. 这推动了基因变异研究和精准医学计划.
科学领域:
- 基因组学
- 生物信息学
- 人类遗传学
背景情况:
- 目前用于识别遗传变异的方法,如短读映射和局部组装,是有限的.
- 这些方法往往错过了复杂基因组区域的结构变异和变异.
- 大规模的新基因组组装对于全面的遗传分析至关重要.
研究的目的:
- 通过 mate-pair 库来证明构建高质量的 de novo 基因组组件的可行性.
- 确定结构变体的全面目录,包括新插入.
- 加强对复杂特征和疾病的关联映射研究的力量.
主要方法:
- 使用高覆盖度的测序,配对图书馆高达20千基.
- 在丹麦基因组项目中对150个个体 (50个三组) 进行了de novo组合.
- 将组装质量与长读测序技术进行比较.
主要成果:
- 与昂贵的长读方法相提并论的新组件.
- 发现了丰富的结构变体, 包括许多新的插入.
- 产生了100个完全解决的主要基因相容性复合 haplotypes,并解决了Y染色体的重要部分.
结论:
- 使用扩展的伴侣对图书馆进行高覆盖度测序对于新基因组组是有效的.
- 生成的变量目录可以改善关联映射信号的解密.
- 这项研究提供了有价值的区域参考基因组,支持精准医学倡议.
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