增强的线粒体基因组分析:生物信息学和长期测序的进步及其诊断影响
William L Macken1,2, Micol Falabella1, Chiara Pizzamiglio1,2
1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Expert review of molecular diagnostics
|August 29, 2023
概括
下一代测序的进步改善了线粒体DNA (mtDNA) 诊断的初级线粒体疾病 (PMDs). 全基因组测序和长读测序为复杂的遗传变异提供了更高的准确性和分辨率.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 医学诊断 医学诊断 医学诊断
背景情况:
- 主要线粒体疾病 (PMDs) 是一组由核DNA (nDNA) 或线粒体DNA (mtDNA) 突变引起的多种遗传疾病.
- 下一代测序 (NGS) 已经提高了mtDNA相关疾病的诊断准确度和效率,但挑战仍然存在.
- 准确的分子诊断对于理解和管理PMD至关重要.
研究的目的:
- 审查目前的mtDNA相关疾病分子诊断的现状.
- 探索全基因组测序 (WGS) 和长读测序等新兴技术对PMD诊断的影响.
- 讨论改善数据分析的生物信息学策略的进展.
主要方法:
- 对 mtDNA 疾病的当前文献和诊断技术的审查.
- 分析PCR无WGS,肌肉DNA的WGS和长读测序的潜在应用.
- 讨论改善的生物信息管道用于WGS数据解释.
主要成果:
- 预计来自血液DNA的PCR无WGS将在诊断环境中变得更加普遍.
- 来自肌肉DNA的WGS可能会在成年肌病呈现方面得到更多的应用.
- 增强的生物信息化策略有望更准确地识别mtDNA,NUMT,副本数和大规模重排 (LSR).
结论:
- 在WGS和长读测序方面的进步,加上改进的生物信息学,有望显著提高PMDs的诊断.
- 这些技术为复杂的mtDNA重组和变异分相提供了更高的分辨率.
- 未来的PMD诊断在于整合这些强大的测序和分析工具.
相关概念视频
02:59Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K
03:00Next-generation Sequencing
91.4K
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
91.4K
01:29Modern Molecular Taxonomy
52
Advancements in molecular biology have revolutionized the identification and characterization of bacteria, with multiple methods leveraging DNA sequencing for enhanced precision. As sequencing technologies improve and costs decline, these approaches are increasingly used in clinical, environmental, and evolutionary studies.Multilocus Sequence Typing (MLST) examines several housekeeping genes, essential chromosomal genes encoding cellular functions, to distinguish strains. Approximately...
52
02:54Evolutionary Relationships through Genome Comparisons
5.8K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
5.8K
02:02Genomics
36.4K
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
36.4K
01:05Maxam-Gilbert Sequencing
11.2K
In the same year as the discovery of the Sanger sequencing method, another group of scientists, Allan Maxam and Walter Gilbert, demonstrated their chemical-cleavage method for DNA sequencing. The Maxam-Gilbert method relies on using different chemicals that can cleave the DNA sequence at specific sites, the separation of resulting DNA fragments of variable size using electrophoresis, and deciphering the DNA sequence from the resulting gel bands.
Challenges of the Maxam-Gilbert Method
The...
Challenges of the Maxam-Gilbert Method
The...
11.2K