Pinto Albano, Cunha Catarina, Chaves Raquel, Butchbach Matthew E R, Adega Filomena
Laboratory of Cytogenomics and Animal Genomics (CAG), Department of Genetics and Biotechnology (DGB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.
BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, 1749-016 Lisbon, Portugal.
Biology (Basel). 2022 May 27;11(6):824. doi: 10.3390/biology11060824.
Transposable elements (TEs) are interspersed repetitive and mobile DNA sequences within the genome. Better tools for evaluating TE-derived sequences have provided insights into the contribution of TEs to human development and disease. Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that is caused by deletions or mutations in the () gene but retention of its nearly perfect orthologue . Both genes are highly enriched in TEs. To establish a link between TEs and SMA, we conducted a comprehensive, in silico analysis of TE insertions within the / loci of SMA, carrier and healthy genomes. We found an Alu insertion in the promoter region and one L1 element in the 3'UTR that may play an important role in alternative promoter as well as in alternative transcriptional termination. Additionally, several intronic Alu repeats may influence alternative splicing via RNA circularization and causes the presence of new alternative exons. These Alu repeats present throughout the genes are also prone to recombination events that could lead to exons deletions and, ultimately, SMA. TE characterization of the SMA genomic region could provide for a better understanding of the implications of TEs on human disease and genomic evolution.
转座元件（TEs）是基因组中散布的重复且可移动的DNA序列。用于评估TE衍生序列的更好工具为了解TEs对人类发育和疾病的贡献提供了见解。脊髓性肌萎缩症（SMA）是一种常染色体隐性运动神经元疾病，由（）基因的缺失或突变引起，但其近乎完美的直系同源基因得以保留。这两个基因在TEs中高度富集。为了建立TEs与SMA之间的联系，我们对SMA患者、携带者和健康基因组的/基因座内的TE插入进行了全面的计算机分析。我们在启动子区域发现了一个Alu插入，在3'UTR中发现了一个L1元件，它们可能在可变启动子以及可变转录终止中发挥重要作用。此外，几个内含子Alu重复序列可能通过RNA环化影响可变剪接，并导致新的可变外显子的出现。这些遍布整个基因的Alu重复序列也容易发生重组事件，这可能导致外显子缺失，并最终导致SMA。对SMA基因组区域的TE特征分析有助于更好地理解TEs对人类疾病和基因组进化的影响。
