| Title: |
Intergenic disease-associated regions are abundant in novel transcripts |
| Authors: |
Bartonicek, N; Clark, MB; Quek, XC; Torpy, JR; Pritchard, AL; Maag, JLV; Gloss, BS; Crawford, J; Taft, RJ; Hayward, NK; Montgomery, GW; Mattick, JS; Mercer, TR; Dinger, ME |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2018 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Background Genotyping 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. Results To 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. Conclusions This 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1186/s13059-017-1363-3 |
| Availability: |
https://doi.org/10.1186/s13059-017-1363-3; https://ora.ox.ac.uk/objects/uuid:c0a0aa7e-9776-4d85-b498-d1fec43c89f8 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.FDC8F004 |
| Database: |
BASE |