BiGeA Department, University of Bologna, Bologna, Italy.
Department of Cultural Heritage, University of Bologna, Ravenna, Italy.
Transl Psychiatry. 2023 May 27;13(1):181. doi: 10.1038/s41398-023-02472-9.
Transposable elements (TEs) are mobile genetic elements that constitute half of the human genome. Recent studies suggest that polymorphic non-reference TEs (nrTEs) may contribute to cognitive diseases, such as schizophrenia, through a cis-regulatory effect. The aim of this work is to identify sets of nrTEs putatively linked to an increased risk of developing schizophrenia. To do so, we inspected the nrTE content of genomes from the dorsolateral prefrontal cortex of schizophrenic and control individuals and identified 38 nrTEs that possibly contribute to the emergence of this psychiatric disorder, two of them further confirmed with haplotype-based methods. We then performed in silico functional inferences and found that 9 of the 38 nrTEs act as expression/alternative splicing quantitative trait loci (eQTLs/sQTLs) in the brain, suggesting a possible role in shaping the human cognitive genome structure. To our knowledge, this is the first attempt at identifying polymorphic nrTEs that can contribute to the functionality of the brain. Finally, we suggest that a neurodevelopmental genetic mechanism, which involves evolutionarily young nrTEs, can be key to understanding the ethio-pathogenesis of this complex disorder.
转座元件（TEs）是可移动的遗传元件，构成人类基因组的一半。最近的研究表明，多态性非参考转座元件（nrTEs）可能通过顺式调控效应导致认知疾病，如精神分裂症。本工作的目的是鉴定与精神分裂症风险增加相关的 nrTE 集合。为此，我们检查了精神分裂症和对照个体的背外侧前额叶皮质基因组中的 nrTE 含量，并鉴定了 38 个可能导致这种精神障碍的 nrTE，其中两个进一步通过基于单倍型的方法得到了证实。然后，我们进行了计算机功能推断，发现 38 个 nrTE 中有 9 个在大脑中作为表达/可变剪接数量性状基因座（eQTLs/sQTLs），这表明它们可能在塑造人类认知基因组结构方面发挥作用。据我们所知，这是首次尝试鉴定可能影响大脑功能的多态性 nrTEs。最后，我们提出一个神经发育遗传机制，涉及进化上较年轻的 nrTEs，这可能是理解这种复杂疾病的病因发病机制的关键。
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