早发型帕金森病家系相关基因的筛查和危险度分析OA北大核心CSTPCD
Screening and risk analysis of genes associated with early onset Parkinson's disease in families
目的:通过早发型帕金森病(early-onset Parkinson's disease,EOPD)遗传家系成员的高通量基因筛查,发现疾病相关突变位点并检测其在人群中对疾病的影响.方法:本研究对早发型PD遗传家系中19名成员进行单核苷酸多态性芯片检测和全外显子基因分型,并通过对家系外散发人群58人进行测序验证,筛选具有较高风险的突变位点.结果:芯片连锁分析发现3个染色体区段、全外显子测序和共表达分析筛选出24个可能与疾病关联的基因.其中5个位点基因型与患病结局之间的Spearman相关系数r>0.6且P<0.05,表示具有关联.通过家系外散发患者测序验证,Ddx56基因(OR=10.923)和Aspn基因(OR=8.198)的突变对患病结局产生显著影响(P<0.05).结论:本研究通过临床患者进行多层次突变位点筛查分析,发现外显子区域的5个突变基因Pdxdc1、Ddx56、Aspn、Rbm28和Shisa9可能与帕金森病密切相关.
Objective:To explore disease-related mutations and its effect on disease in the population through high-throughput gene screening of the members of an early-onset Parkinson's disease(EOPD)genetic family.Methods:SNP microarray and whole exon sequencing(WES)were performed in 19 members of early-onset PD genetic families.Moreover,the sequencing of 58 sporadic patients was verified to screen out mutation genes with high risk.Results:Linkage analysis found 3 chromosome re-gions,and WES and coexpression analysis screened out 24 genes that may be associated with PD.The Spearman correlation coeffi-cient R>0.6 and P<0.05 between five loci genotype and disease outcome indicated that there was a correlation.Conclusion:Through multilevel mutation site screening analysis in clinical patients,we find that five mutant genes Pdxdc1,Ddx56,Aspn,Rbm28 and Shisa9 in exon region may be closely associated with PD.More functional research will be conducted in the future.
许茜;林瑶;范丽华;林昆明;吴方真;周美;倪慧心;刘海鑫;范自立;高正涛
福建中医药大学中西医结合学院,福建 福州 350122三明市中西医结合医院神经内科,福建 三明 365000三明市第一医院中医科,福建 三明 365000福建省第二人民医院风湿内分泌科,福建 福州 350001
临床医学
早发型帕金森病全外显子测序连锁分析
Early-onset Parkinson's diseaseWhole exon sequencingLinkage analysis
《海南医学院学报》 2024 (012)
888-896 / 9
This study was supported by National Natural Science Foundation of China Youth Program(81904263);Fujian Province Traditional Chinese Medicine Research Project Plan(2021zyjc02);Fujian University of Traditional Chinese Medicine Traditional Chinese Medicine Health Management Joint Provincial Clinical Key Specialty Construction Project(Geriatrics)(XJG2023018)国家自然科学基金青年项目(81904263);福建省中医药科研项目计划(2021zyjc02);福建中医药大学中医健康管理学联合省级临床重点专科建设项目(老年病科)(XJG2023018)
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