Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle
- Lingzhao Fang1,2,3,4,8,
- Wentao Cai2,5,8,
- Shuli Liu1,5,8,
- Oriol Canela-Xandri3,4,8,
- Yahui Gao1,2,
- Jicai Jiang2,
- Konrad Rawlik3,
- Bingjie Li1,
- Steven G. Schroeder1,
- Benjamin D. Rosen1,
- Cong-jun Li1,
- Tad S. Sonstegard6,
- Leeson J. Alexander7,
- Curtis P. Van Tassell1,
- Paul M. VanRaden1,
- John B. Cole1,
- Ying Yu5,
- Shengli Zhang5,
- Albert Tenesa3,4,
- Li Ma2 and
- George E. Liu1
- 1Animal Genomics and Improvement Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, USDA, Beltsville, Maryland 20705, USA;
- 2Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland 20742, USA;
- 3The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian EH25 9RG, United Kingdom;
- 4Medical Research Council Human Genetics Unit at the Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh EH4 2XU, United Kingdom;
- 5College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
- 6Acceligen, Eagan, Minnesota 55121, USA;
- 7Fort Keogh Livestock and Range Research Laboratory, Agricultural Research Service, USDA, Miles City, Montana 59301, USA
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↵8 These authors contributed equally to this work.
Abstract
By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., CCDC88C) for male fertility, brain (e.g., TRIM46 and RAB6A) for milk production, and multiple growth-related tissues (e.g., FGF6 and CCND2) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.250704.119.
- Received March 22, 2019.
- Accepted May 1, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
