人类互动体中的边缘性乱的程度是由特定人群突变引起的
Hongzhu Cui1,2, Suhas Srinivasan3,4,5, Ziyang Gao1
1Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA 01609, USA.
Biomolecules
|January 23, 2024
概括
健康人群中的遗传变异可以改变蛋白质相互作用,并影响不同种族群体的疾病易感性. 这项研究揭示了种群特异性突变如何导致表型差异和疾病风险.
科学领域:
- 人口遗传学 人口遗传学
- 系统生物学 系统生物学
- 生物信息学是一种生物信息学.
背景情况:
- 以前的遗传研究偏向欧洲祖先,限制了对全球遗传多样性的理解.
- 全球人口研究突出了基因变异的种族差异,需要功能结果链接.
- "edgotype"概念侧重于突变诱导的,相互作用特定的蛋白质扰乱.
研究的目的:
- 系统地分析非同义单核酸变体 (nsSNVs) 及其"边缘性"影响.
- 研究nsSNVs对人类互动体的功能影响,并将其与已知的致病变体进行比较.
- 探索特定种群的遗传变异及其在表型差异和疾病易感性中的作用.
主要方法:
- 使用一个半监督学习工具 (SNP-IN) 进行in silico edgetic profiling.
- 从1000个基因组项目分析了大约5万个nsSNV,与1万多个蛋白质相互作用复合体对比.
- 进行网络分析以识别与疾病相关的模块并评估累积网络损害.
主要成果:
- 来自健康个体的大量nsSNV可以重新连接人类蛋白质交互组.
- 具有相互作用破坏突变的蛋白质与各种功能和各种疾病有关.
- 种群中不同的基因边缘特征与表型变异相关.
- 与疾病相关的模块显示了健康人群中相互作用破坏突变的较高密度.
结论:
- 大规模的 in silico 边缘研究是可行的,并提供了对人口特异性突变的洞察力.
- 人群特异性突变在塑造人类互动组和影响疾病易感性方面发挥着作用.
- 模块内的网络损伤的变化可能解释了特定人群的疾病差异.
相关概念视频
Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K
Mutation, Gene Flow, and Genetic Drift
58.4K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
58.4K
Genome Copying Errors
4.2K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.2K
Mutations
37.7K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
37.7K
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Genetic Drift
39.8K
Natural selection—probably the most well-known evolutionary mechanism—increases the prevalence of traits that enhance survival and reproduction. However, evolution does not merely propagate favorable traits, nor does it always benefit populations.
39.8K


