Identification of Novel Genetic Loci for Parkinson's Disease Using Whole-Exome and Whole-Genome Sequencing.

IF 0.5 4区医学 Q4 PHARMACOLOGY & PHARMACY

Psychiatry and Clinical Psychopharmacology Pub Date : 2025-04-16 eCollection Date: 2025-06-01 DOI:10.5152/pcp.2025.24889

Qian Xu, Mei Zhou, Huixin Ni, Haixin Liu, Zhengtao Gao, Fangzhen Wu, Yao Lin

{"title":"Identification of Novel Genetic Loci for Parkinson's Disease Using Whole-Exome and Whole-Genome Sequencing.","authors":"Qian Xu, Mei Zhou, Huixin Ni, Haixin Liu, Zhengtao Gao, Fangzhen Wu, Yao Lin","doi":"10.5152/pcp.2025.24889","DOIUrl":null,"url":null,"abstract":"Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by a multifaceted genetic foundation. We hypothesized that combining whole-genome sequencing (WGS) with whole-exome sequencing (WES) in a multi-generational family affected by PD could identify rare and novel variants of genes associated with PD.Methods: This study included a family showing multiple members affected by PD and exhibiting an apparent dominant inheritance pattern. Seventeen family members were genotyped by WES and 6 of them was additionally analyzed by WGS. The common variants were validated by Sanger sequencing.Results: Forty-seven genes that may be associated with PD were identified by co-separation analysis, clustering analysis, correlation analysis of resequencing data, and 2 of them were common. For these two genes, polymerase chain reaction (PCR) and Sanger sequencing were performed in family members, and quantitative PCR (qPCR) was conducted in 6 sporadic PD patients and 6 controls to detect mRNA expression. It was found that the Ddx56 mutation frequency (chr7: 44610462) was significantly different between PD and control in the family. Additionally, the DEAD-box helicase 56(Ddx56) gene was down-regulated in PD patients, outside the family members, while Ccdc42 mutation frequency and mRNAexpression had no significant difference.Conclusion: Therefore, it was speculated that the mutation of Ddx56 in exon (chr7: 44610462) might be related to the occurrence of PD.","PeriodicalId":20847,"journal":{"name":"Psychiatry and Clinical Psychopharmacology","volume":"35 2","pages":"92-101"},"PeriodicalIF":0.5000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149315/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychiatry and Clinical Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5152/pcp.2025.24889","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by a multifaceted genetic foundation. We hypothesized that combining whole-genome sequencing (WGS) with whole-exome sequencing (WES) in a multi-generational family affected by PD could identify rare and novel variants of genes associated with PD.

Methods: This study included a family showing multiple members affected by PD and exhibiting an apparent dominant inheritance pattern. Seventeen family members were genotyped by WES and 6 of them was additionally analyzed by WGS. The common variants were validated by Sanger sequencing.

Results: Forty-seven genes that may be associated with PD were identified by co-separation analysis, clustering analysis, correlation analysis of resequencing data, and 2 of them were common. For these two genes, polymerase chain reaction (PCR) and Sanger sequencing were performed in family members, and quantitative PCR (qPCR) was conducted in 6 sporadic PD patients and 6 controls to detect mRNA expression. It was found that the Ddx56 mutation frequency (chr7: 44610462) was significantly different between PD and control in the family. Additionally, the DEAD-box helicase 56(Ddx56) gene was down-regulated in PD patients, outside the family members, while Ccdc42 mutation frequency and mRNAexpression had no significant difference.

Conclusion: Therefore, it was speculated that the mutation of Ddx56 in exon (chr7: 44610462) might be related to the occurrence of PD.

查看原文本刊更多论文

利用全外显子组和全基因组测序鉴定帕金森病的新基因位点。

背景：帕金森病（PD）是一种常见的神经退行性疾病，其特征是多方面的遗传基础。我们假设，结合全基因组测序（WGS）和全外显子组测序（WES），可以在一个多代PD患者家庭中发现罕见的和新的PD相关基因变异。方法：本研究纳入了一个多成员患有帕金森病且表现出明显显性遗传模式的家庭。17名家庭成员经WES分型，6名家庭成员经WGS分型。常见变异通过Sanger测序进行验证。结果：通过共分离分析、聚类分析、重测序数据相关分析，共鉴定出47个可能与PD相关的基因，其中2个为常见基因。对这两个基因在家族成员中进行聚合酶链反应（PCR）和Sanger测序，并对6例散发性PD患者和6例对照进行定量PCR （qPCR）检测mRNA表达。结果发现，Ddx56突变频率（chr7: 44610462）在PD和对照组中存在显著差异。此外，除家族成员外，DEAD-box解旋酶56（Ddx56）基因在PD患者中下调，而Ccdc42突变频率和mrna表达无显著差异。结论：因此，推测外显子Ddx56 （chr7: 44610462）突变可能与PD的发生有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Psychiatry and Clinical Psychopharmacology Medicine-Psychiatry and Mental Health

CiteScore

1.00

自引率

14.30%

发文量

期刊介绍： Psychiatry and Clinical Psychopharmacology aims to reach a national and international audience and will accept submissions from authors worldwide. It gives high priority to original studies of interest to clinicians and scientists in applied and basic neurosciences and related disciplines. Psychiatry and Clinical Psychopharmacology publishes high quality research targeted to specialists, residents and scientists in psychiatry, psychology, neurology, pharmacology, molecular biology, genetics, physiology, neurochemistry, and related sciences.