Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle
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 testisspecific 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.
- Authors:
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[9];
[8];
[8];
[8];
[6]
more »
- US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service. Henry A. Wallace Beltsville Agricultural Research Center. Animal Genomics and Improvement Lab.; Univ. of Maryland, College Park, MD (United States). Dept. of Animal and Avian Sciences; Univ. of Edinburgh, Scotland (United Kingdom). Royal (Dick) School of Veterinary Studies. The Roslin Inst. Medical Research Council Human Genetics Unit
- Univ. of Maryland, College Park, MD (United States). Dept. of Animal and Avian Sciences; China Agricultural Univ., Beijing (China). College of Animal Science and Technology
- US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service. Henry A. Wallace Beltsville Agricultural Research Center. Animal Genomics and Improvement Lab.; China Agricultural Univ., Beijing (China). College of Animal Science and Technology
- Univ. of Edinburgh, Scotland (United Kingdom). Royal (Dick) School of Veterinary Studies. The Roslin Inst. Medical Research Council Human Genetics Unit at the Medical Research Council Inst. of Genetics and Molecular Medicine
- US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service. Henry A. Wallace Beltsville Agricultural Research Center. Animal Genomics and Improvement Lab.; Univ. of Maryland, College Park, MD (United States). Dept. of Animal and Avian Sciences
- Univ. of Maryland, College Park, MD (United States). Dept. of Animal and Avian Sciences
- Univ. of Edinburgh, Scotland (United Kingdom). Royal (Dick) School of Veterinary Studies. The Roslin Inst.
- US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service. Henry A. Wallace Beltsville Agricultural Research Center. Animal Genomics and Improvement Lab.
- Acceligen, Eagan, MN (United States)
- US Dept. of Agriculture (USDA), Miles City, MT (United States). Agricultural Research Service. Fort Keogh Livestock and Range Research Lab.
- China Agricultural Univ., Beijing (China). College of Animal Science and Technology
- China Agricultural Univ., Beijing (China). College of Animal Science and Technology
- Univ. of Edinburgh, Scotland (United Kingdom). Royal (Dick) School of Veterinary Studies. The Roslin Inst. Medical Research Council Human Genetics Unit at the Medical Research Council Inst. of Genetics and Molecular Medicine
- Publication Date:
- Research Org.:
- Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); USDA; Marie Sklodowska-Curie grant
- OSTI Identifier:
- 1816883
- Grant/Contract Number:
- SC0014664; 2013-67015-20951; 2016-67015-24886; 2019-67015-29321; US-4997-17; BBS/ E/D/10002070; BBS/E/D/30002275; MR/P015514/1; HDR-9004; 801215; MR/R025851/1
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Genome Research
- Additional Journal Information:
- Journal Volume: 30; Journal Issue: 5; Journal ID: ISSN 1088-9051
- Publisher:
- Cold Spring Harbor Laboratory Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Fang, Lingzhao, Cai, Wentao, Liu, Shuli, Canela-Xandri, Oriol, Gao, Yahui, Jiang, Jicai, Rawlik, Konrad, Li, Bingjie, Schroeder, Steven G., Rosen, Benjamin D., Li, Cong-jun, Sonstegard, Tad S., Alexander, Leeson J., Van Tassell, Curtis P., VanRaden, Paul M., Cole, John B., Yu, Ying, Zhang, Shengli, Tenesa, Albert, Ma, Li, and Liu, George E. Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle. United States: N. p., 2020.
Web. doi:10.1101/gr.250704.119.
Fang, Lingzhao, Cai, Wentao, Liu, Shuli, Canela-Xandri, Oriol, Gao, Yahui, Jiang, Jicai, Rawlik, Konrad, Li, Bingjie, Schroeder, Steven G., Rosen, Benjamin D., Li, Cong-jun, Sonstegard, Tad S., Alexander, Leeson J., Van Tassell, Curtis P., VanRaden, Paul M., Cole, John B., Yu, Ying, Zhang, Shengli, Tenesa, Albert, Ma, Li, & Liu, George E. Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle. United States. https://doi.org/10.1101/gr.250704.119
Fang, Lingzhao, Cai, Wentao, Liu, Shuli, Canela-Xandri, Oriol, Gao, Yahui, Jiang, Jicai, Rawlik, Konrad, Li, Bingjie, Schroeder, Steven G., Rosen, Benjamin D., Li, Cong-jun, Sonstegard, Tad S., Alexander, Leeson J., Van Tassell, Curtis P., VanRaden, Paul M., Cole, John B., Yu, Ying, Zhang, Shengli, Tenesa, Albert, Ma, Li, and Liu, George E. Fri .
"Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle". United States. https://doi.org/10.1101/gr.250704.119. https://www.osti.gov/servlets/purl/1816883.
@article{osti_1816883,
title = {Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle},
author = {Fang, Lingzhao and Cai, Wentao and Liu, Shuli and Canela-Xandri, Oriol and Gao, Yahui and Jiang, Jicai and Rawlik, Konrad and Li, Bingjie and Schroeder, Steven G. and Rosen, Benjamin D. and Li, Cong-jun and Sonstegard, Tad S. and Alexander, Leeson J. and Van Tassell, Curtis P. and VanRaden, Paul M. and Cole, John B. and Yu, Ying and Zhang, Shengli and Tenesa, Albert and Ma, Li and Liu, George E.},
abstractNote = {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 testisspecific 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.},
doi = {10.1101/gr.250704.119},
journal = {Genome Research},
number = 5,
volume = 30,
place = {United States},
year = {Fri May 01 00:00:00 EDT 2020},
month = {Fri May 01 00:00:00 EDT 2020}
}
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