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, sa.3, ss.1091-1106, 2023 (SSCI) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s10803-022-05636-6
  • Dergi Adı: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
  • Derginin Tarandığı İndeksler: 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
  • Sayfa Sayıları: ss.1091-1106
  • Anahtar Kelimeler: 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 Üniversitesi Adresli: Evet

Özet

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.