Evidence map›Paper›PMID 42001173›Full record

ArticleGenome medicine2026

Tissue-specific gene dosage disruption is a key feature and pathogenic mechanism of structural variants in the human genome.

Xubing Liu, Zhao Chen, Qian Jiang, Haoyu Shen, Hongyu Liu, Zhenguo Wang, Zhe Li, Jihong Wu, Hong Jiang, Xin Li

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Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Xubing Liu *Department of Neurology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Zhao Chen *Department of Neurology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Qian Jiang *Department of Neurology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Haoyu Shen *Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Hongyu LiuShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhenguo WangShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhe LiShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jihong WuEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. jihongwu@fudan.edu.cn.
Hong JiangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, People's Republic of China. jianghong73868@126.com.
Xin LiShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. lixin@sinh.ac.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStructural variants (SVs) are important contributors to genetic disorders, yet their effects on gene dosage, particularly in a tissue-specific context, remain underexplored.

methodsLeveraging large-scale transcriptomic data, we analyzed the tissue specific dosage disrupting effect of SVs in the human genome. To characterize this tissue-specific dosage effect, we developed a computational framework, PathoSV, which captures this impact via a Transcript Disruption Ratio (TDR). We further evaluated these tissue-specific dosage effects in patients with inherited neurodegenerative diseases.

resultsWe find that dosage disruption is a key feature of rare structural variants and such effects are largely tissue specific. Further identifying such tissue-specific dosage disrupting SVs among 530 previously unresolved individuals with inherited retinal disease (IRD) or hereditary ataxia (HA), we made a molecular diagnosis in 10.1% and 3.2% of cases, respectively. We identified pathogenic dosage-disrupting SVs in critical, tissue-specific genes such as EYS in the retina and ITPR1 and SPAST in the cerebellum.

conclusionsWe show that tissue-specific disruption of gene dosage is a characteristic functional consequence of rare SVs in the human genome and an important contributor to pathogenicity. Quantifying transcript-level dosage disruption clarifies the transcriptomic context in which pathogenic effects arise in complex neurodegenerative disorders and suggests a broader role for tissue-specific dosage disruption in disease. PathoSV is available at: https://github.com/xlilab/PathoSV .

Indexed as

Gene DosageGenome, HumanGenomic Structural VariationHumansOrgan SpecificityRetinal DiseasesGene dosageHereditary ataxiaInherited retinal diseaseNeurodegenerative disordersStructural variantsTissue-specific dosage disruptionTranscript disruption ratioTranscriptome-aware variant interpretation

Identifiers

PMID42001173
PMCPMC13224669

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.