Modenini Giorgia, Abondio Paolo, Guffanti Guia, Boattini Alessio, Macciardi Fabio
University of Bologna.
Res Sq. 2023 Jan 23:rs.3.rs-2474682. doi: 10.21203/rs.3.rs-2474682/v1.
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 which possibly contribute to the emergence of this psychiatric disorder. Furthermore, we performed in silico functional inferences and found, for instance, 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. Therefore, 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 the key to understanding the ethiopathogenesis of this complex disorder.
转座元件（TEs）是构成人类基因组一半的可移动遗传元件。最近的研究表明，多态性非参考转座元件（nrTEs）可能通过顺式调节作用导致认知疾病，如精神分裂症。这项工作的目的是确定可能与精神分裂症发病风险增加相关的nrTEs集合。为此，我们检查了精神分裂症患者和对照个体背外侧前额叶皮质基因组中的nrTEs含量，确定了38个可能导致这种精神疾病出现的nrTEs。此外，我们进行了计算机功能推断，例如发现38个nrTEs中的9个在大脑中作为表达/可变剪接数量性状基因座（eQTLs/sQTLs）起作用，这表明它们在塑造人类认知基因组结构中可能发挥作用。因此，据我们所知，这是首次尝试识别可能影响大脑功能的多态性nrTEs。最后，我们认为一种涉及进化上年轻的nrTEs的神经发育遗传机制可能是理解这种复杂疾病病因发病机制的关键。
