追踪超稀有变种的进化历史,使用大型祖先重组图的变异约会
bioRxiv : the preprint server for biology
|February 6, 2026
概括
我们开发了一种可扩展的方法,使用祖先重组图 (ARG) 来确定极为罕见的遗传变异的日期. 这种方法提供了准确的,祖先不可知的等位基因年龄,对于大规模的基因组研究和临床应用至关重要.
科学领域:
- 基因组学就是基因组学.
- 计算生物学 计算生物学
- 人口遗传学 人口遗传学
背景情况:
- 超罕见的变异在全基因组测序中很丰富,但由于对等位基因频率的限制和祖先偏见,难以解释.
- 现有的等位基因年龄估计方法无法扩展到大型生物库队列.
研究的目的:
- 开发一个可扩展的算法来测定祖先重组图 (ARG),适用于生物库规模的数据集.
- 为了能够对超罕见的遗传变异进行可靠的,祖先不可知的年龄估计.
主要方法:
- 在tsdate软件中实现了一个可扩展的变量算法来约会ARG.
- 开发了用于生物库规模ARG推断的分布式方法,使用tsanfer.
- 从英格兰基因组学10万个基因组项目对47535个基因组应用了方法.
主要成果:
- 推断连续ARG跨越206Mb和估计年龄为2320万个变体,包括1180万个单元.
- 在极端抽样不平衡下,证明了基于ARG的等位基年龄准确性.
- 在具有相同频率的变体中揭示了选择和临床异质性的特征.
结论:
- 生物库规模的ARG能够准确地对超罕见的变异进行祖先不可知的年龄估计.
- 这种方法对统计基因组学和临床应用具有广泛的实用性.
- 大数据集中的哈普洛型结构为最近的突变提供了精确的年龄估计.
相关概念视频
What is Evolutionary History?
43.6K
Scientists record evolutionary history by analyzing fossil, morphological, and genetic data. The fossil record documents the history of life on Earth and provides evidence for evolution. However, both fossil and living organisms offer evidence that outlines Earth’s evolutionary history.
43.6K
Conservative Site-specific Recombination and Phase Variation
6.8K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.8K
Radioactive Decay and Radiometric Dating
37.2K
Radioactivity is a spontaneous disintegration of an unstable nuclide and is a random process, as all the nuclei in the sample do not decay simultaneously. The number of disintegrations per unit time is called the activity (A), which is directly proportional to the number of nuclei in the sample. The decay constant (λ) is an average probability of decay per nucleus in unit time.
37.2K
Histone Variants at the Centromere
5.1K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
5.1K
What is Variation?
18.6K
Apart from the measures of central tendency, distribution, outliers, and the changing characteristics of data with time, an important characteristic of any data set is its variation or spread. In some data sets, the data values are concentrated closely near the mean; in others, the data values are more widely spread out from the mean.
The range, standard deviation, standard error, and variance are the different measures of variation.
Range: The range is the difference between its maximum and...
The range, standard deviation, standard error, and variance are the different measures of variation.
Range: The range is the difference between its maximum and...
18.6K
Evolutionary Psychology
1.0K
Evolutionary psychology explores the origins of human behavior and mental processes by framing them within the context of natural selection, a theory famously propounded by Charles Darwin. This field asserts that many behaviors common across human societies — ranging from instinctive fear reactions to complex social interactions — arose as evolutionary adaptations. These adaptations enhanced the survival and reproductive success of our ancestors, thereby becoming embedded in the...
1.0K


