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      A multi-tissue atlas of regulatory variants in cattle

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          Abstract

          Characterization of genetic regulatory variants acting on the livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype-Tissue Expression atlas (CattleGTEx) as part of the pilot phase of Farm animal GTEx (FarmGTEx) project for the research community based on publicly available 7,180 RNA-Seq samples. We describe the transcriptomic landscape of over 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multi-omics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.

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          Most cited references57

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            Fast gapped-read alignment with Bowtie 2.

            As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.
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              clusterProfiler: an R package for comparing biological themes among gene clusters.

              Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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                Author and article information

                Contributors
                Journal
                9216904
                Nat Genet
                Nat Genet
                Nature genetics
                1061-4036
                1546-1718
                01 September 2022
                11 August 2022
                29 November 2022
                06 December 2022
                : 54
                : 9
                : 1438-1447
                Affiliations
                [1 ]Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, Maryland 20705, USA
                [2 ]The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian EH25 9RG, UK
                [3 ]MRC Human Genetics Unit at the Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh EH4 2XU, UK
                [4 ]College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
                [5 ]Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA
                [6 ]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
                [7 ]Institute of Animal Science, Chinese Academy of Agricultural Science, Beijing 100193, China
                [8 ]Scotland’s Rural College (SRUC), Roslin Institute Building, Midlothian EH25 9RG, UK
                [9 ]Faculty of Veterinary & Agricultural Science, The University of Melbourne, Parkville 3052, Victoria, Australia
                [10 ]Agriculture Victoria, AgriBio, Centre for AgriBiosciences, Bundoora, Victoria 3083, Australia
                [11 ]INRAE, AgroParisTech, GABI, Université Paris-Saclay, Jouy-en-Josas, F-78350, France
                [12 ]Guangdong Provincial Key Laboratory of Waterfowl Healthy Breeding, College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China
                [13 ]School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China
                Author notes
                [* ]Corresponding Authors: GEL: Animal Genomics and Improvement Laboratory, USDA-ARS, Building 306, Room, 111, BARC-East, Beltsville, MD 20705, USA. George.Liu@ 123456usda.gov , Voice Phone: +1-301-504-9843, Fax: +1-301-504-8414. AT: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian EH25 9RG, UK. Albert.Tenesa@ 123456ed.ac.uk LF: MRC Human Genetics Unit at the Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh EH4 2XU, UK. Lingzhao.fang@ 123456ed.ac.uk ; lingzhaofang@ 123456gmail.com

                Note: One of the authors, Shengli Zhang, passed away.

                Article
                EMS157770
                10.1038/s41588-022-01153-5
                7613894
                35953587
                c7a62734-bd99-4ea5-bbfe-c5658bdc7c38

                This work is licensed under a CC BY 4.0 International license.

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                Categories
                Article

                Genetics
                cattle,expression qtls,gwas,rna-seq,twas
                Genetics
                cattle, expression qtls, gwas, rna-seq, twas

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