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The landscape of DNA methylation amid a perfect storm of autism aetiologies.

ABSTRACT: Increasing evidence points to a complex interplay between genes and the environment in autism spectrum disorder (ASD), including rare de novo mutations in chromatin genes such as methyl-CpG binding protein 2 (MECP2) in Rett syndrome. Epigenetic mechanisms such as DNA methylation act at this interface, reflecting the plasticity in metabolic and neurodevelopmentally regulated gene pathways. Genome-wide studies of gene sequences, gene pathways and DNA methylation are providing valuable mechanistic insights into ASD. The dynamic developmental landscape of DNA methylation is vulnerable to numerous genetic and environmental insults: therefore, understanding pathways that are central to this 'perfect storm' will be crucial to improving the diagnosis and treatment of ASD.

SUBMITTER: Vogel Ciernia A

PROVIDER: S-EPMC4966286 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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The landscape of DNA methylation amid a perfect storm of autism aetiologies.

Vogel Ciernia Annie A LaSalle Janine J

Nature reviews. Neuroscience 20160506 7

Increasing evidence points to a complex interplay between genes and the environment in autism spectrum disorder (ASD), including rare de novo mutations in chromatin genes such as methyl-CpG binding protein 2 (MECP2) in Rett syndrome. Epigenetic mechanisms such as DNA methylation act at this interface, reflecting the plasticity in metabolic and neurodevelopmentally regulated gene pathways. Genome-wide studies of gene sequences, gene pathways and DNA methylation are providing valuable mechanistic ...[more]

PMID: 27150399

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Project description:BackgroundCyathostomins are prevalent and pathogenic intestinal helminths of horses, causing acute and chronic disease, including acute larval cyathostominosis, which has a mortality rate of 50%. Factors determining individual susceptibility to acute larval cyathostominosis are unknown. Investigation of these factors could lead to novel treatment and prevention strategies.ObjectivesTo investigate clinicopathological and faecal microbiota changes associated with disease in individual horses in an acute larval cyathostominosis outbreak.Study designCase series.MethodsThe study population was a herd of 23 mixed breed horses in Ireland. The outbreak occurred in November 2018. Fourteen horses were clinically affected. Clinical status was monitored and recorded. Blood and faecal sampling allowed clinicopathological, faecal 16s rRNA gene sequencing and faecal egg count analyses.ResultsTwo horses were euthanised, whilst 12 recovered. Common clinical signs included loose faecal consistency, weight loss and pyrexia. Consistent clinicopathological findings were borderline anaemia, leucocytosis, thrombocytosis, hyperfibrinogenaemia, hyperglobulinaemia and a reverse A: G ratio. Decreased alpha-diversity of the faecal microbiota and greater relative abundance of the genus Streptococcus, class Bacilli, order Lactobacillales and family Streptococcaceae, and family Prevotelleceae was found in clinically affected horses compared to their clinically normal cohorts. An increase in obligate fibrolytic bacteria was seen in the clinically normal group compared to the clinical group. Histopathological findings of the colon and caecum revealed a severe necrotising typhlocolitis associated with cyathostomin larvae and bacterial overgrowth in the mucosa of the large intestine.Main limitationsThe study population in this outbreak is small. There are several confounding factors limiting this to a descriptive case series. Faecal microbiota has been shown to reflect the large intestinal microbiota but do not represent changes directly.ConclusionsThese findings suggest that acute larval cyathostominosis is associated with dysbiosis of the gut microbiota as well as the inflammatory stimulus of numerous emerging larvae leading to structural and functional pathology of the large intestine.

Dataset Information

The landscape of DNA methylation amid a perfect storm of autism aetiologies.

Publications

The landscape of DNA methylation amid a perfect storm of autism aetiologies.

Similar Datasets

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