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对以前与欧洲人ALS相关的结构变异的分析突出了非洲人的基因组结构差异

Nomakhosazana R Monnakgotla¹, Amokelani C Mahungu¹, Jeannine M Heckmann¹

¹From the Neurology Research Group (N.R.M., A.C.M., J.M.H., M.N.), Division of Neurology, Department of Medicine; Neuroscience Institute (N.R.M., A.C.M., J.M.H., M.N.); Computational Biology Division (G.B., N.J.M.), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa; Center for Applied Bioinformatics (G.W., E.R., J.M.), St. Jude Children's Research Hospital, Memphis, TN; Department of Neuroscience (M.V.B.), Mayo Clinic, Jacksonville, FL; Center for Molecular Neurology (R.R.), University of Antwerp, Belgium; Department of Cell and Molecular Biology (J.P.T.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Neurology (J.W., M.B.), University of Miami, FL.

Neurology. Genetics

|June 22, 2023

概括

这项研究发现,SCAF4,SQSTM1,STMN2和SMN1/SMN2基因拷贝数的特定遗传变异与南非人的肌缩性侧面硬化症 (ALS) 风险之间没有关联. 这些发现强调了在遗传研究中需要多样化的种群.

科学领域:

遗传学是一个遗传学.
神经科学是一个神经科学.
人口健康人口健康

背景情况:

肌缩侧面硬化症 (ALS) 是一种神经退行性疾病,其中遗传因素尚未完全理解,特别是非编码结构变异 (SVs).
之前在欧洲人口中进行的研究表明,SCAF4,SQSTM1和STMN2中的特定SV和SMN1/SMN2基因拷贝数与ALS风险之间存在关联.
在不同人群中研究这些遗传因素对于全面了解ALS病变的产生至关重要.

研究的目的:

调查SCAF4,SQSTM1和STMN2中假定ALS敏感性等位基因与非洲祖先队列中的ALS风险的关联.
在患有ALS的非洲祖先个体中描述SMN1/SMN2基因区域的结构.
为了将研究结果与之前在欧洲和其他非洲人口中报告的相关性进行比较.

主要方法:

分析了来自南非ALS患者的全基因组测序 (WGS) 数据 (n=114) 和祖先匹配的对照 (n=150).
研究的特定等位基因包括SCAF4 (3'UTR多T重复),SQSTM1 (intron 5 AAAC插入) 和STMN2 (intron 3 CA重复).
评估了SMN1和SMN2基因拷贝数,并将数据与1000基因组项目和H3Africa基因型芯片项目样本进行了比较.

主要成果:

在南非队列中,研究的SCAF4,SQSTM1和STMN2等位基因与ALS风险之间没有发现显著的关联 (p > 0.2).
在ALS病例和对照组中,SMN1和SMN2基因拷贝数没有差异 (p > 0.9).
与欧洲人 (~7%) 相比,非洲样本中观察到没有SMN2基因拷贝的个体的频率更高 (20%).

结论:

该研究没有复制之前报告的SCAF4,SQSTM1和STMN2短SV与南非样本中的ALS的关联.
在这个队列中,SMN1/SMN2副本数量和ALS易感性之间没有发现联系,这与欧洲元分析一致.
在非洲人中观察到的SMN基因架构差异强调了遗传研究中人口多样性的重要性,并可能对基因疗法产生影响.

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