通过长读序列测序识别Dystrophin基因中具有断点的反转:两例病例报告
Liqing Chen1, Xiaoping Luo1, Hongling Wang1
1Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
BMC medical genomics
|September 9, 2024
概括
长读数测序 (LRS) 能够有效地检测罕见的杜申肌肉发育不良症 (DMD) 基因逆转,这些逆转在标准测试中错过了. 在反转断点的简单重复序列为潜在治疗提供了对突变机制的洞察力.
科学领域:
- 遗传学 遗传学 是一个
- 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:
- 杜氏肌肉发育不良 (DMD) 是一种X链遗传疾病,由DMD基因突变引起.
- 大量的删除是常见的DMD突变,而反向则不那么频繁,通常不会被MLPA和WES等标准方法检测到.
研究的目的:
- 调查长读序列 (LRS) 在识别DMD基因逆转中的实用性.
- 描述DMD患者的结构变异及其潜在机制.
主要方法:
- 利用长读测序 (LRS) 来识别两个无关家族的DMD基因中的染色体内逆转.
- 使用桑格序列测序确认了已识别的反转.
- 对存在简单重复序列 (SRS) 的分析断点.
主要成果:
- 在使用LRS.的DMD基因中确定了两种不同的染色体内逆转.
- 第一个案例涉及到一个周心反转 (DMD 47到Xq27.3的DMD内置).
- 第二个案例涉及一个偏心逆转 (DMD内置42到Xp21.1),由母亲遗传. 这两种情况都在逆转断点显示了SRS.
结论:
- 长读测序 (LRS) 是检测复杂和非典型突变的强大工具,如DMD基因逆转.
- 在反转断点上存在的SRS提供了关于驱动DMD结构变化的机制的宝贵信息.
- 这种增强的理解可以有助于开发针对杜申尼肌肉发育不良症的向治疗策略.
相关概念视频
01:39Mutations
Overview
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
02:18Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:30Point and Frameshift Mutations
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...