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Non-LTR Retrotransposons03:18

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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
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LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
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Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
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Evolutionarily recent retrotransposons contribute to schizophrenia.

Giorgia Modenini1, Paolo Abondio, Guia Guffanti

  • 1University of Bologna.

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|February 7, 2023
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Polymorphic transposable elements (TEs) in the human genome may influence schizophrenia risk. This study identified 38 non-reference TEs (nrTEs) in brain tissue potentially linked to schizophrenia, offering new insights into its genetic basis.

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Area of Science:

  • Genomics
  • Neuroscience
  • Molecular Biology

Background:

  • Transposable Elements (TEs) comprise a significant portion of the human genome.
  • Polymorphic non-reference TEs (nrTEs) are increasingly implicated in complex diseases, including schizophrenia.
  • A cis-regulatory role for nrTEs in cognitive disorders is hypothesized.

Approach:

  • Genome-wide analysis of nrTE content in the Dorsolateral Prefrontal Cortex of individuals with and without schizophrenia.
  • Identification of specific nrTEs associated with schizophrenia risk.
  • In silico functional analysis to determine the potential regulatory roles of identified nrTEs.

Key Points:

  • 38 potentially pathogenic nrTEs were identified in the schizophrenic brain.
  • Nine of these nrTEs function as expression/alternative splicing quantitative trait loci (eQTLs/sQTLs) in the brain.
  • This research represents the first effort to link polymorphic nrTEs to brain function and schizophrenia.

Conclusions:

  • Polymorphic nrTEs may contribute to schizophrenia pathogenesis through cis-regulatory mechanisms.
  • Evolutionarily young nrTEs could play a role in neurodevelopmental genetic mechanisms underlying schizophrenia.
  • Further research into nrTEs offers a novel avenue for understanding complex psychiatric disorders.