Whole Genome Analysis of Dizygotic Twins With Autism Reveals Prevalent Transposon Insertion Within Neuronal Regulatory Elements: Potential Implications for Disease Etiology and Clinical Assessment


Okay K., ÜNAL VARIŞ P., MİRAL S., PAVLOPOULOU A., OKTAY Y., KARAKÜLAH G.

JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, no.3, pp.1091-1106, 2023 (SSCI) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1007/s10803-022-05636-6
  • Journal Name: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
  • Journal Indexes: Social Sciences Citation Index (SSCI), Scopus, Academic Search Premier, ASSIA, PASCAL, BIOSIS, Child Development & Adolescent Studies, CINAHL, EBSCO Education Source, Education Abstracts, Educational research abstracts (ERA), EMBASE, ERIC (Education Resources Information Center), Linguistics & Language Behavior Abstracts, MEDLINE, Psycinfo, Public Affairs Index
  • Page Numbers: pp.1091-1106
  • Keywords: Autism spectrum disorder, Variant calling, Transposable element, Whole genome sequencing, Quartet families, SPECTRUM DISORDER, COPY NUMBER, STRUCTURAL VARIANTS, MUTATIONS, GENE, RETROTRANSPOSONS, RISK, DNA, ASSOCIATION, NETWORK
  • Dokuz Eylül University Affiliated: Yes

Abstract

Transposable elements (TEs) have been implicated in autism spectrum disorder (ASD). However, our understanding of their roles is far from complete. Herein, we explored de novo TE insertions (dnTEIs) and de novo variants (DNVs) across the genomes of dizygotic twins with ASD and their parents. The neuronal regulatory elements had a tendency to harbor dnTEIs that were shared between twins, but ASD-risk genes had dnTEIs that were unique to each twin. The dnTEIs were 4.6-fold enriched in enhancers that are active in embryonic stem cell (ESC)-neurons (p <0.001), but DNVs were 1.5-fold enriched in active enhancers of astrocytes (p =0.0051). Our findings suggest that dnTEIs and DNVs play a role in ASD etiology by disrupting enhancers of neurons and astrocytes.