LINE-1 and Alu methylation signatures in autism spectrum disorder and their associations with the expression of autism-related genes

Authors

Thanit Saeliw, The Ph.D. Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Tiravut Permpoon, Research Division, SiMR, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Nutta Iadsee, Research Division, SiMR, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Tewin Tencomnao, Natural Products for Neuroprotection and Anti-Ageing Research Unit, Chulalongkorn University, Bangkok, Thailand.
Valerie W. Hu, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Tewarit Sarachana, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Daniel Green, Institute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
Chanachai Sae-Lee, Research Division, SiMR, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. chanachai.sae@mahidol.ac.th.

Document Type

Journal Article

Publication Date

8-17-2022

Journal

Scientific reports

Volume

12

Issue

1

DOI

10.1038/s41598-022-18232-6

Abstract

Long interspersed nucleotide element-1 (LINE-1) and Alu elements are retrotransposons whose abilities cause abnormal gene expression and genomic instability. Several studies have focused on DNA methylation profiling of gene regions, but the locus-specific methylation of LINE-1 and Alu elements has not been identified in autism spectrum disorder (ASD). Here we interrogated locus- and family-specific methylation profiles of LINE-1 and Alu elements in ASD whole blood using publicly-available Illumina Infinium 450 K methylation datasets from heterogeneous ASD and ASD variants (Chromodomain Helicase DNA-binding 8 (CHD8) and 16p11.2del). Total DNA methylation of repetitive elements were notably hypomethylated exclusively in ASD with CHD8 variants. Methylation alteration in a family-specific manner including L1P, L1H, HAL, AluJ, and AluS families were observed in the heterogeneous ASD and ASD with CHD8 variants. Moreover, LINE-1 and Alu methylation within target genes is inversely related to the expression level in each ASD variant. The DNA methylation signatures of the LINE-1 and Alu elements in ASD whole blood, as well as their associations with the expression of ASD-related genes, have been identified. If confirmed in future larger studies, these findings may contribute to the identification of epigenomic biomarkers of ASD.

APA Citation

Saeliw, Thanit; Permpoon, Tiravut; Iadsee, Nutta; Tencomnao, Tewin; Hu, Valerie W.; Sarachana, Tewarit; Green, Daniel; and Sae-Lee, Chanachai, "LINE-1 and Alu methylation signatures in autism spectrum disorder and their associations with the expression of autism-related genes" (2022). GW Authored Works. Paper 1472.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1472

Department

Biochemistry and Molecular Medicine