Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy
BACKGROUND: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. RESULTS: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patien...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2017
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| Sorozat: | GENOME BIOLOGY
18 No. 1 |
| doi: | 10.1186/s13059-017-1286-z |
| mtmt: | 3267667 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/15882 |
| Tartalmi kivonat: | BACKGROUND: Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. RESULTS: Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. CONCLUSIONS: RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics. |
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| Terjedelem/Fizikai jellemzők: | Paper 170-21 p |
| ISSN: | 1474-7596 |