在个体人类基因组中,复杂的双重重复的景观重复
Kazuki Ichikawa1, Riki Kawahara1, Takeshi Asano1
1Department of Computational Biology and Medical Sciences, The University of Tokyo, 277-8561, Chiba, Japan.
Nature communications
|September 14, 2023
概括
扩展串联重复 (TRs) 与疾病有关. 新的方法揭示了复杂的TR结构,揭示了它们的多样性和潜在的疾病关联,即使在小群体中.
科学领域:
- 基因组学和人类遗传学
- 分子生物学分子生物学
背景情况:
- 扩展串联重复 (TRs) 与大约60种疾病有关.
- 了解TR多样性对于解释遗传性缺失至关重要.
- 由于现有的测序和分析方法的局限性,精确确定复杂,长的TR和小卫星一直是具有挑战性的.
研究的目的:
- 开发和应用一个高精度的算法来确定复杂的TR结构使用PacBio HiFi长读.
- 在日本人口中调查长TRs的全基因组景观,包括它们的多样性,结构和潜在的疾病关联.
主要方法:
- 利用了一种新的,高精度的算法,旨在分析来自PacBio HiFi长,准确的测序读取的复杂TR结构.
- 分析了270个日本对照样本的基因组数据,以识别和表征整个基因组的TRs.
主要成果:
- 确定了大约322,000个难以从周围的单核酸变体中归因的TRs.
- 在TR位点的更大的遗传分歧和年轻复制滑落事件的增加之间发现了显著的相关性.
- 观察到复杂的TR比单单元的TR更丰富,在较长的位置 (≥500-bp) 的复杂的TR (<10-bp单位) 和单单元的TR (小卫星) 中发现了特定的结构趋势.
结论:
- 复杂的TR和小卫星是丰富多样的,甚至在基因均的群体中.
- 发现了8909个具有扩展TRs的位点,其中几个含有已知与疾病相关的TRs,突出显示了它们在遗传疾病中的潜在作用.
- 这些发现提供了对长 TR 景观及其对人类遗传变异和疾病的贡献的关键见解.
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