在人类骨肌肉活检中,OXPHOS相关的基因表达和恶性高热敏感性之间的关联
Leon Chang1, Rebecca Motley1, Catherine L Daly2
1Leeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
International journal of molecular sciences
|March 28, 2024
概括
恶性高温症 (MH) 易感性与线粒体能量生产中的基因表达改变有关. 这项研究揭示了氧化酸化和脂肪酸代谢基因的差异,这可能解释了MH.
科学领域:
- 遗传学和基因组学 在
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 恶性高温症 (MH) 是由挥发性麻醉剂触发的骨肌肉的药物遗传性疾病.
- 在RYR1的致病变体是主要原因,但遗传因素仍然不完全理解,有助于多样化的MH表型.
- 目前对MH遗传学的理解是有限的,有着无法解释的病例和各种各样的临床表现.
研究的目的:
- 通过使用肌肉活检来研究MH易感个体的全基因组基因表达.
- 确定与超出RYR1.1.的MH易感性相关的新型遗传标记和途径.
- 探索线粒体生物能学在MH病理生理学和表型变异性中的作用.
主要方法:
- 从MH敏感 (MHS) 和MH非敏感 (MHN) 个体进行肌肉活检的转录组分析.
- 差异基因表达分析,专注于氧化酸化 (OXPHOS) 和脂肪酸代谢途径.
- 在更大的队列中验证关键基因表达变化,并调查与性别相关的和亚表型效应.
主要成果:
- 鉴定了822个MHS和MHN个体之间的差异表达基因,富含OXPHOS和脂肪酸代谢.
- 在MHS样本中验证了ATP5MD和COQ6的减少表达.
- 在SDHB和UQCC3中观察到与性别相关的表达效应,以及在MH亚现型中差异性ATP5MD表达.
结论:
- MH易感性与线粒体生物能学途径中的失调基因表达有关.
- 变化的线粒体基因表达可能会导致恶性高温症中观察到的表型多样性.
- 转录基因分析提供了超越RYR1突变的MH复杂遗传基础的见解.
相关概念视频
Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Nucleotide Excision Repair
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...
Mismatch Repair
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...
Human Genetics
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...


