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Transcriptomic Genes Identified in Familial Eosinophilic Esophagitis

ABSTRACT: Transcriptomic Genes Identified in Familial Eosinophilic Esophagitis

PROVIDER: PRJNA1054589 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27289000_1.fastq.gz	Fastqsanger.gz
	SRR27289000_2.fastq.gz	Fastqsanger.gz
	SRR27289001_1.fastq.gz	Fastqsanger.gz
	SRR27289001_2.fastq.gz	Fastqsanger.gz
	SRR27289002_1.fastq.gz	Fastqsanger.gz

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Transcriptomic Genes Identified in Familial Eosinophilic Esophagitis

Project description:Background and Aims: Evidence for a genetic contribution to eosinophilic esophagitis (EoE) exists from family and genome-wide association studies. Extensive investigation into rare variants contributing to EoE has not been performed. The Aim is to evaluate families with multiple cases of EoE by genomic and transcriptomic sequencing to identify genes predisposing to EoE. Methods: We whole exome sequenced (WES) distant relative pairs (e.g., cousins) in extended EoE pedigrees and other affected relatives to identify rare, shared, potentially pathologic variants. Whole-transcriptome sequencing by RNA-Seq was performed in nuclear families with multiple EoE cases. We compared the overlap of genes from DNA and RNA sequencing for relevance to disease manifestations. Results: WES was performed in 50 familial cases in 21 EoE extended pedigrees. We observed 219 rare, candidate predisposition variants in 210 genes with complete sharing among all affected family members. Transcriptome sequencing was performed for 43 EoE cases in 18 nuclear kindreds, including 6 relatives without EoE. We observed 10,070 total differentially expressed genes compared to controls. We identified three genes (MUC16, ADGRE1, and TENM3) with evidence of rare variant sharing and differential gene expression among all affected family members. We identified 43 other genes with partial sharing of rare variants among affected family members and with differential gene expression. Several genes identified as prominent in EoE were also differentially expressed in unaffected relatives. Conclusions: Multiple genes related to immune response, barrier dysfunction, and cell adhesion were identified in familial EoE cases and unaffected family members supporting a genetic familial predisposition and a possible multi-hit background to disease pathophysiology.

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Project description:Adult Eosinophilic Esophagitis Registry Atlas

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Nanostring nCounter human miRNA assay (v1) of eosinophilic esophagitis

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