Altered DNA Methylation in a Severe Subtype of Idiopathic Autism: Evidence for Sex Differences in Affected Metabolic Pathways

Autor/inn/en	Hu, Valerie W.; Hong, Yi; Xu, Minyi; Shu, Henry T.
Titel	Altered DNA Methylation in a Severe Subtype of Idiopathic Autism: Evidence for Sex Differences in Affected Metabolic Pathways
Quelle	In: Autism: The International Journal of Research and Practice, 25 (2021) 4, S.887-910 (24 Seiten) PDF als Volltext Verfügbarkeit
Zusatzinformation	ORCID (Hu, Valerie W.)
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1362-3613
DOI	10.1177/1362361320971085
Schlagwörter	Genetics; Autism; Pervasive Developmental Disorders; Correlation; Profiles; Cytology; Severity (of Disability); Gender Differences; Brain Hemisphere Functions; Metabolism; Pathology; Biology; Comparative Analysis + Suchen Sie Ihr Suchwort? Humangenetik; Autismus; Korrelation; Charakterisierung; Profilanalyse; Zytologie; Schweregrad; Geschlechterkonflikt; Stoffwechsel; Pathologie; Biologie
Abstract	Although differences in DNA methylation have been associated with both syndromic and idiopathic autism, differential methylation has not been examined previously with respect to sex differences. The goals of this study were to (1) identify differences in the DNA methylation profiles of lymphoblastoid cell lines derived from a subgroup of severely affected individuals with idiopathic autism and their respective sex-matched siblings, (2) describe autism spectrum disorder--relevant pathways and functions that may be impacted by differentially methylated genes, and (3) investigate sex-dependent differences in methylation patterns and signaling pathways. Our results revealed significant differences in DNA methylation in cells from individuals with idiopathic autism spectrum disorders and from their unaffected sex-matched siblings. The samples were divided either by sex or by separation into discovery and validation groups. The genes in differentially methylated regions were statistically enriched in autism susceptibility genes and canonical pathways commonly associated with autism spectrum disorders, including synaptogenesis, semaphorin, and mammalian target of rapamycin signaling pathways. Differentially methylated region--associated genes in females were additionally associated with pathways that implicate mitochondrial dysfunction and metabolic disorders that may offer some protection against autism spectrum disorders. Further investigations of sex differences are required to develop a fuller understanding of the pathobiology, gene regulatory mechanisms, and differential susceptibility of males and females toward autism spectrum disorders. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2024/1/01