Intergenic Disease-associated Regions are Abundant in Novel Regulatory Transcripts
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB21619 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2022810_1.fastq.gz | Fastqsanger.gz | |||
| ERR2022810_2.fastq.gz | Fastqsanger.gz | |||
| ERR2022820_1.fastq.gz | Fastqsanger.gz | |||
| ERR2022820_2.fastq.gz | Fastqsanger.gz | |||
| ERR2022830_1.fastq.gz | Fastqsanger.gz |
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2005-06-03 | E-GEOD-2347 | biostudies-arrayexpress
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Project description:BackgroundGenotyping of large populations through genome-wide association studies (GWAS) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a large proportion of GWAS single nucleotide polymorphisms (SNPs) and associated haplotype blocks are in intronic and intergenic regions, hindering their functional evaluation. While some of these risk-susceptibility regions encompass cis-regulatory sites, their transcriptional potential has never been systematically explored.ResultsTo detect rare tissue-specific expression, we employed the transcript-enrichment method CaptureSeq on 21 human tissues to identify 1775 multi-exonic transcripts from 561 intronic and intergenic haploblocks associated with 392 traits and diseases, covering 73.9 Mb (2.2%) of the human genome. We show that a large proportion (85%) of disease-associated haploblocks express novel multi-exonic non-coding transcripts that are tissue-specific and enriched for GWAS SNPs as well as epigenetic markers of active transcription and enhancer activity. Similarly, we captured transcriptomes from 13 melanomas, targeting nine melanoma-associated haploblocks, and characterized 31 novel melanoma-specific transcripts that include fusion proteins, novel exons and non-coding RNAs, one-third of which showed allelically imbalanced expression.ConclusionsThis resource of previously unreported transcripts in disease-associated regions ( http://gwas-captureseq.dingerlab.org ) should provide an important starting point for the translational community in search of novel biomarkers, disease mechanisms, and drug targets.
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