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Intracranial aneurysm associated single-nucleotide polymorphisms alter regulatory DNA in the human circle of Willis

ABSTRACT: Intracranial aneurysm associated single-nucleotide polymorphisms alter regulatory DNA in the human circle of Willis

PROVIDER: PRJNA419258 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6311280.fastq.gz	Fastqsanger.gz
	SRR6311271.fastq.gz	Fastqsanger.gz
	SRR6311281.fastq.gz	Fastqsanger.gz
	SRR6311272.fastq.gz	Fastqsanger.gz
	SRR6311282.fastq.gz	Fastqsanger.gz

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Intracranial aneurysm associated single-nucleotide polymorphisms alter regulatory DNA in the human circle of Willis

Project description:Background and Purpose: Genome-wide association studies significantly link intracranial aneurysm (IA) to single-nucleotide polymorphisms (SNPs) in six genomic loci. To gain insight into the relevance of these IA associated SNPs, we aimed to identify regulatory regions and analyze overall gene expression in the human circle of Willis (CoW), on which these aneurysms develop. Methods: We performed chromatin immunoprecipitation and sequencing for histone modifications H3K4me1 and H3K27ac to identify regulatory regions, including distal enhancers and active promoters, in post mortem specimens of the human CoW. These experiments were complemented with RNA sequencing on the same specimens. We determined whether these regulatory regions overlap with IA associated SNPs, using computational methods. By combining our results with publicly available data, we investigated the effect of IA associated SNPs on the newly identified regulatory regions and linked them to potential target genes. Results: We find that IA associated SNPs are significantly enriched in CoW regulatory regions. Some of the IA associated SNPs that overlap with a regulatory region are likely to alter transcription factor binding, and in proximity to these regulatory regions are 102 genes that are expressed in the CoW. In addition, gene expression in the CoW is enriched for genes related to cell adhesion and the extracellular matrix. Conclusions: CoW regulatory regions link IA associated SNPs to genes with a potential role in the development of IAs. Our data refine previous predictions on SNPs associated with IA and provide a substantial resource from which candidates for follow-up studies can be prioritized.

2018-01-04 | GSE107196 | GEO

RNA sequencing analysis of rupture-prone intracranial aneurysms and the remaining circle of Willis in rats

Project description:Comprehensive gene expression profile was obtained by RNA sequencing analysis using total RAN purified from intracranial aneurysm lesions and remaining circle of Willis in rats.

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Project description:As the EU IP @neurIST Project aims at integrating biomedical informatics technologies in the assessment of rupture risks and treatments of cerebral aneurysms in humans. Genetic involvement in the disease is known, mRNA biomarkers will be searched as possible risk factors in easy to assess PBMCs (peripheral blood cells). The aim of this pilot study is specifically to check the clinical samples going from the patientï¾s bed side to the genomic analysis platform. Briefly, we hybridized biotin labelled cRNA from 2 controls (C1, C2), 1 patient bearing an intracranial aneurysm (I) and 1 patients bearing an intracranial aneurysm and subarachnoid haemorrhage (S). For each sample, one technical replicate was performed. Thus a total of 8 arrays was used.

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