Abstract
BackgroundAutism spectrum disorder (ASD) has increased over tenfold over the past several decades and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now also thought to be an important factor. Epigenetic alterations, such as DNA methylation, have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility.Methods and resultsSperm samples were obtained from fathers that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. A genome-wide analysis (> 90%) for differential DNA methylation regions (DMRs) was used to identify DMRs in the sperm of fathers (n = 13) with autistic children in comparison with those (n = 13) without ASD children. The 805 DMR genomic features such as chromosomal location, CpG density and length of the DMRs were characterized. Genes associated with the DMRs were identified and found to be linked to previously known ASD genes, as well as other neurobiology-related genes. The potential sperm DMR biomarkers/diagnostic was validated with blinded test sets (n = 8–10) of individuals with an approximately 90% accuracy.ConclusionsObservations demonstrate a highly significant set of 805 DMRs in sperm that can potentially act as a biomarker for paternal offspring autism susceptibility. Ancestral or early-life paternal exposures that alter germline epigenetics are anticipated to be a molecular component of ASD etiology.
Highlights
Autism spectrum disorder (ASD) is a complex neurological disorder involving deficits in communication, social behaviors and stereotypic movements [1, 2]
Observations demonstrate a highly significant set of 805 DNA methylation regions (DMRs) in sperm that can potentially act as a biomarker for paternal offspring autism susceptibility
Ancestral or early-life paternal exposures that alter germline epigenetics are anticipated to be a molecular component of ASD etiology
Summary
Autism spectrum disorder (ASD) is a complex neurological disorder involving deficits in communication, social behaviors and stereotypic movements [1, 2]. The prevalence of ASD in 1975 was reported as 1 in 5000 and in 2009 as 1 in 110 [3]. Environmental factors are believed to be involved in the etiology of autism. A number of molecular alterations in the genome have been correlated to the neurobiology of ASD [2]; the specific environmental factors, molecular processes and etiology of autism remain to be fully elucidated. Genetics is anticipated to be a component of ASD eti‐ ology, environmental epigenetics is thought to be an important factor. Epigenetic alterations, such as DNA methylation, have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility
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