Intergenic disease-associated regions are abundant in novel transcripts

Autor: N. Bartonicek, M. B. Clark, X. C. Quek, J. R. Torpy, A. L. Pritchard, J. L. V. Maag, B. S. Gloss, J. Crawford, R. J. Taft, N. K. Hayward, G. W. Montgomery, J. S. Mattick, T. R. Mercer, M. E. Dinger
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Genome Biology, Vol 18, Iss 1, Pp 1-16 (2017)
Druh dokumentu: article
ISSN: 1474-760X
09370587
DOI: 10.1186/s13059-017-1363-3
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
Externí odkaz: