摘要
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 regions,and WES and coexpression analysis screened out 24 genes that may be associated with PD.The Spearman correlation coefficient 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.
作者
许茜
范丽华
林昆明
吴方真
周美
倪慧心
刘海鑫
范自立
高正涛
林瑶
XU Qian;FAN Lihua;LIN Kunming;WU Fangzhen;ZHOU Mei;NI Huixin;LIU Haixin;FAN Zili;GAO Zhengtao;LIN Yao(College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Department of Neurology,Sanming Hospital of Integrated Chinese and Western Medicine,Sanming 365000,China;Department of Traditional Chinese Medicine,Sanming First Hospital,Sangming 365000,China;Rheumatology and Endocrinology Department,The Second People's Hospital of Fujian Province,Fuzhou 350001,China)
出处
《海南医学院学报》
CAS
北大核心
2024年第12期888-896,共9页
Journal of Hainan Medical University
基金
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)。
关键词
早发型帕金森病
全外显子测序
连锁分析
Early‑onset Parkinson′s disease
Whole exon sequencing
Linkage analysis
