基于微型基因的剪接测定为了解 PKHD1 基因的内含子变异提供了新的视角。

IF 3.8 3区医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-11-09 DOI:10.1186/s40246-024-00675-9

Yiyin Zhang, Ran Zhang, Xiaomeng Shi, Xuyan Liu, Changying Li, Yan Zhang, Zhi Wang, Dan Qiao, Fengjiao Pan, Bingying Zhang, Ning Xu, Bingzi Dong, Leping Shao

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引用次数: 0

摘要

背景：常染色体隐性遗传多囊肾病（ARPKD）是一种罕见的遗传性疾病，由 PKHD1 变异引起。目前，异常剪接已被报道在遗传病中发挥重要作用。我们的目标是在 mRNA 水平分析 PKHD1 的内含子变异：结果：我们将 12 个候选变体引入相应的迷你基因，并在 HEK 293T 和 Hela 细胞中进行了功能测试。我们发现了 11 个可诱导剪接改变的变异体，它们会导致各种后果，如跳过外显子、内含子保留和蛋白质截断：这突显了 mRNA 水平评估对相关遗传疾病基因诊断的重要性。

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Minigene-based splice assays provide new insights on intronic variants of the PKHD1 gene.

Background: Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare hereditary disorder caused by variants in PKHD1. Currently, aberrant splicing has been reported to play important roles in genetic disease. Our goal is to analyze intronic variants in PKHD1 at the mRNA level.

Results: The 12 candidate variants were introduced into the corresponding minigene and functionally assayed in HEK 293T and Hela cells. We identified 11 variants that induce splicing alterations, resulting in various consequences such as skipping of exons, intron retention and protein truncation.

Conclusions: This underlined the importance of mRNA-level assessment for genetic diagnostics in related genetic disorders.

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.