Academic Journal
Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits
| Title: | Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits |
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| Authors: | Min Wang, Timothy P. Hancock, Amanda J. Chamberlain, Christy J. Vander Jagt, Jennie E. Pryce, Benjamin G. Cocks, Mike E. Goddard, Benjamin J. Hayes |
| Source: | BMC Genomics, Vol 19, Iss 1, Pp 1-17 (2018) |
| Publisher Information: | BMC, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Biotechnology LCC:Genetics |
| Subject Terms: | Topological association domains, CTCF binding motifs, Allelic-specific expression, Allele-specific expression quantitative trail loci, Expression quantitative trail loci, Functional annotation, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| More Details: | Abstract Background Topological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants. Results We used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping genes, transfer RNA genes, CTCF binding motifs, short interspersed elements, H3K4me3 and H3K27ac. We showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows’ white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The linearly-furthermost, and most-significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1471-2164 |
| Relation: | http://link.springer.com/article/10.1186/s12864-018-4800-0; https://doaj.org/toc/1471-2164 |
| DOI: | 10.1186/s12864-018-4800-0 |
| Access URL: | https://doaj.org/article/968165e3ff854e728b4ad6f906c3d391 |
| Accession Number: | edsdoj.968165e3ff854e728b4ad6f906c3d391 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 14712164 |
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| DOI: | 10.1186/s12864-018-4800-0 |
| Published in: | BMC Genomics |
| Language: | English |