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Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits

Overview of attention for article published in BMC Genomics, May 2018
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Title
Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits
Published in
BMC Genomics, May 2018
DOI 10.1186/s12864-018-4800-0
Pubmed ID
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

Abstract

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. 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 < 0.001). Our results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 24%
Researcher 3 14%
Student > Master 2 10%
Student > Ph. D. Student 2 10%
Professor 1 5%
Other 1 5%
Unknown 7 33%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 29%
Biochemistry, Genetics and Molecular Biology 4 19%
Business, Management and Accounting 1 5%
Veterinary Science and Veterinary Medicine 1 5%
Computer Science 1 5%
Other 1 5%
Unknown 7 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 June 2019.
All research outputs
#9,326,920
of 15,226,555 outputs
Outputs from BMC Genomics
#4,936
of 8,655 outputs
Outputs of similar age
#157,062
of 279,918 outputs
Outputs of similar age from BMC Genomics
#9
of 21 outputs
Altmetric has tracked 15,226,555 research outputs across all sources so far. This one is in the 36th percentile – i.e., 36% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,655 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 38th percentile – i.e., 38% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 279,918 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.