category
bioRxiv
date
Mar 7, 2026
slug
status
Published
summary
创新性地利用UK Biobank大规模全基因组数据揭示变异频率与序列背景的系统性关联,发现单体型变异在CG上下文中频率差异、三核苷酸背景对变异频率的显著影响,以及参考基因组中特定五核苷酸序列的链不对称性,提出链特异性突变机制可能影响选择压力的新假说。
tags
测序技术
type
Post
📄 原文题目
Sequence effects on patterns of variation and DNA strand asymmetries observed from whole-genome sequenced UK Biobank participants
🔗 原文链接
💡 AI 核心解读
创新性地利用UK Biobank大规模全基因组数据揭示变异频率与序列背景的系统性关联,发现单体型变异在CG上下文中频率差异、三核苷酸背景对变异频率的显著影响,以及参考基因组中特定五核苷酸序列的链不对称性,提出链特异性突变机制可能影响选择压力的新假说。
📝 英文原版摘要
UK Biobank has released whole genome sequence data for 500,000 participants, including allele counts for hundreds of millions of variants and these were considered in the context of the pentanucleotide background on which they occurred. Frequencies of singleton variants were obtained and compared with frequencies of more common variants. Results were highly correlated across chromosomes, reflecting systematic effects. C>T singleton variants were less frequent in the CG context but the opposite was true for more common variants, suggesting that they are relatively well tolerated and not subject to strong negative selection. The frequencies of singleton variant types were strongly influenced by their trinucleotide context and the total counts of variants in their trinucleotide context could be well approximated by combining five mutational signatures obtained from genomes of cancer cells. For some variant types, there were marked asymmetries in counts between plus and minus DNA strands. The patterns of these asymmetries for singleton variants differed between chromosomes, with five being negatively correlated with the rest. These asymmetries did not appear related to strand-specific gene content. It was noted that there were also strand asymmetries for some pentanucleotide sequences in the reference genome and that these were consistent across chromosomes. The sequence TTCGT is seen 673300 times on the plus strand but only 465807 times on the minus strand. These findings must reflect strand-specific mechanisms affecting mutation and selection which are not currently well understood and which could be investigated further. This research has been conducted using the UK Biobank Resource.
- 作者:NotionNext
- 链接:https://tangly1024.com/article/31d48bd6-1f96-8110-931f-daddf9702292
- 声明:本文采用 CC BY-NC-SA 4.0 许可协议,转载请注明出处。
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