[en] We report the generation of an organism-wide catalog of 976,813 cis-acting regulatory elements for the bovine detected by the assay for transposase accessible chromatin using sequencing (ATAC-seq). We regroup these regulatory elements in 16 components by nonnegative matrix factorization. Correlation between the genome-wide density of peaks and transcription start sites, correlation between peak accessibility and expression of neighboring genes, and enrichment in transcription factor binding motifs support their regulatory potential. Using a previously established catalog of 12,736,643 variants, we show that the proportion of single-nucleotide polymorphisms mapping to ATAC-seq peaks is higher than expected and that this is owing to an approximately 1.3-fold higher mutation rate within peaks. Their site frequency spectrum indicates that variants in ATAC-seq peaks are subject to purifying selection. We generate eQTL data sets for liver and blood and show that variants that drive eQTL fall into liver- and blood-specific ATAC-seq peaks more often than expected by chance. We combine ATAC-seq and eQTL data to estimate that the proportion of regulatory variants mapping to ATAC-seq peaks is approximately one in three and that the proportion of variants mapping to ATAC-seq peaks that are regulatory is approximately one in 25. We discuss the implication of these findings on the utility of ATAC-seq information to improve the accuracy of genomic selection.
Disciplines :
Genetics & genetic processes
Author, co-author :
Yuan, Can ; Université de Liège - ULiège > GIGA > GIGA Medical Genomics - Unit of Animal Genomics
Lopdell, Thomas ; Université de Liège - ULiège > GIGA > GIGA Administration ; Research and Development, Livestock Improvement Corporation, Hamilton 3240, New Zealand
Petrov, Vyacheslav A; Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium
Oget-Ebrad, Claire ; Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium
Moreira, Gabriel Costa Monteiro; Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium
Gualdrón Duarte, José Luis; Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium
Sartelet, Arnaud ; Université de Liège - ULiège > Département d'Enseignement et de Clinique des animaux de Production (DCP)
Cheng, Zhangrui; Royal Veterinary College, Hatfield, Herts AL9 7TA, United Kingdom
Salavati, Mazdak; Royal Veterinary College, Hatfield, Herts AL9 7TA, United Kingdom
Wathes, D Claire; Royal Veterinary College, Hatfield, Herts AL9 7TA, United Kingdom
Crowe, Mark A; School of Veterinary Medicine, University College Dublin, Dublin 4, Ireland
FP7 - 613689 - GPLUSE - Genotype and Environment contributing to the sustainability of dairy cow production systems through the optimal integration of genomic selection and novel management protocols based on the development
Name of the research project :
Damona
Funders :
ERC - European Research Council [BE] EU - European Union [BE] Région wallonne [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding number :
CAUSEL grant from the Walloon Region (no.1710030)
Funding text :
We thank Calixte Bayrou, Ken Kusakabe, Ruth Appeltant, Anne-
Sophie Van Laere, and all members of Michel Georges’ laboratory
for their help for sample collections, technical support, and fruitful
discussion. We also thank the support provided by the GIGA
Genomics and Bioinformatics core facilities. This work was funded
by the Damona European Research Council advanced grant from
the EU (AdG-GA323030), the GplusE FP7 grant from the EU (no.
613689), the CAUSEL grant from the Walloon Region (no.1710030), and financial support from Inoveo. C.C. and T.D. are senior
research associate and research director from the Fonds de la
Recherche Scientifique. Computational resources have been provided
by the Consortium des Équipements de Calcul Intensif,
funded by the Fonds de la Recherche Scientifique de Belgique
(no. 2.5020.11) and by the Walloon Region.
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