常见的疾病比核心基因全基因模型所暗示的更复杂
Naomi R Wray1, Cisca Wijmenga2, Patrick F Sullivan3
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
Cell
|June 16, 2018
概括
大多数成人发病都是多基因的,这意味着许多基因都有所贡献. "全基因"模型可能过度简化了这种复杂性,表明患者分层是精确医学的关键.
科学领域:
- 遗传学和基因组学
- 复杂的疾病生物学
- 精准医学
背景情况:
- 绝大多数证据支持大多数成人发病的多基因遗传结构.
- 这些疾病涉及强大的生物系统和多种备份机制.
- 最近的"全基因"或"核心基因"模型提出每种疾病的核心基因数量很少.
研究的目的:
- 评估多基因性对常见疾病的影响.
- 批判性地评估"全基因"或"核心基因"模型.
- 确定推进精准医学的最佳方法.
主要方法:
- 对多基因架构现有证据的审查和考虑.
- 对"全基因"模型的假设和局限性的分析.
- 探索多基因性对实验设计和临床策略的影响.
主要成果:
- 常见疾病的多基因性质表明了重要的生物复杂性.
- "万能基因"模型假设的几个核心基因可能低估了这种复杂性.
- 专注于发现一小部分"核心基因"可能不是最有效的实验策略.
结论:
- 多基因疾病的复杂性需要超越像"全基因"假设这样的简化模型.
- 实验设计不应该仅仅以寻找"核心基因"为指导.
- 患者分层对于实现复杂疾病的精准医学目标至关重要.
相关概念视频
The Nucleosome Core Particle
14.5K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
14.5K
The Nucleosome Core Particle
2.4K
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
2.4K
Common Ion Effect
47.0K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
47.0K
Protein Complex Assembly
16.8K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.8K
Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
Gene Families
10.0K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
10.0K


