相关实验视频

Updated: Jul 24, 2025

Following the Dynamics of Structural Variants in Experimentally Evolved Populations

Following the Dynamics of Structural Variants in Experimentally Evolved Populations

Published on: February 3, 2023

在CYP2D6-CYP2D7-CYP2D8基因位点中复杂的结构变异的表征,使用单分子长读测序

Amy J Turner¹, Ashley D Derezinski¹, Andrea Gaedigk²

¹RPRD Diagnostics LLC, Milwaukee, WI, United States.

Frontiers in pharmacology

|July 10, 2023

概括

一种新的CRISPR-Cas9方法使用长读测序准确地基因型复杂的CYP2D6位点. 这改善了药物代谢分析,可以适应其他具有挑战性的基因组区域.

科学领域:

基因组学就是基因组学.
药物基因组学药物基因组学
分子生物学分子生物学

背景情况:

复杂的基因组区域,包括伪基因和结构变异 (SVs),通过短读序列来挑战精确的遗传分析.
CYP2D6位点对药物代谢至关重要,但含有非常相似的伪基因 (CYP2D7,CYP2D8) 和复杂的SVs,妨碍了准确的基因型定型.
不准确的CYP2D6基因型定型可能导致错误的酶活性分配,影响药物剂量并不成比例地影响某些人群.

研究的目的:

开发一种新的方法,用于对整个CYP2D6-CYP2D7-CYP2D8位点进行准确和全面的基因型鉴定.
克服现有的测序技术在解决这个药物基因组区域内的复杂结构变异方面的局限性.
为了能够精确地确定CYP2D6双型,以改善临床表型和药物治疗指导.

主要方法:

开发了一个没有PCR的CRISPR-Cas9丰富策略,用于有针对性的长读序列.
将该方法应用于临床相关的样本 (血液,唾液,肝脏组织).
生成高覆盖率,连续长读 (高达52kb),覆盖整个位置,包括结构变化.

主要成果:

成功生成了连续的长读数,完全描述了CYP2D6-CYP2D7-CYP2D8位点,无论SVs.
实现了局部结构的分阶段剖析,通过单个测试精确地解决了复杂的CYP2D6双型.
鉴定了三种新的CYP2D6亚基基,并充分描述了17种CYP2D7和18种CYP2D8独特的单元类型.

结论:

开发的CRISPR-Cas9丰富和长读测序方法提供了准确和全面的CYP2D6基因型鉴定.
这种方法显著提高了在具有挑战性的基因组区域内解决复杂遗传变异的能力.
该方法有可能增强临床表型,告知药物治疗,并可适应其他难以分析的基因组位置.

关键词:

克里斯普尔是什么意思?克里斯普尔是什么意思?在CYP2D6中.没有PCR,没有PCR.临床试验临床试验是指临床试验.药物遗传学药物遗传学精准医学是一门精准医学.单分子长读序列测序

更多相关视频

Mapping Mammalian 3D Genome Interactions with Micro-C-XL

Mapping Mammalian 3D Genome Interactions with Micro-C-XL

Published on: November 3, 2023

Detection of Copy Number Alterations Using Single Cell Sequencing

Detection of Copy Number Alterations Using Single Cell Sequencing

Published on: February 17, 2017

相关概念视频

Comparing Copy Number Variations and SNPs

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

RNA-seq

RNA-seq

RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases.
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while...