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Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle

BACKGROUND: The study of molecular processes regulating heat stress response in dairy cattle is paramount for developing mitigation strategies to improve heat tolerance and animal welfare. Therefore, we aimed to identify quantitative trait loci (QTL) regions associated with three physiological indic...

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Autores principales: Luo, Hanpeng, Hu, Lirong, Brito, Luiz F., Dou, Jinhuan, Sammad, Abdul, Chang, Yao, Ma, Longgang, Guo, Gang, Liu, Lin, Zhai, Liwei, Xu, Qing, Wang, Yachun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392250/
https://www.ncbi.nlm.nih.gov/pubmed/35986427
http://dx.doi.org/10.1186/s40104-022-00748-6
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author Luo, Hanpeng
Hu, Lirong
Brito, Luiz F.
Dou, Jinhuan
Sammad, Abdul
Chang, Yao
Ma, Longgang
Guo, Gang
Liu, Lin
Zhai, Liwei
Xu, Qing
Wang, Yachun
author_facet Luo, Hanpeng
Hu, Lirong
Brito, Luiz F.
Dou, Jinhuan
Sammad, Abdul
Chang, Yao
Ma, Longgang
Guo, Gang
Liu, Lin
Zhai, Liwei
Xu, Qing
Wang, Yachun
author_sort Luo, Hanpeng
collection PubMed
description BACKGROUND: The study of molecular processes regulating heat stress response in dairy cattle is paramount for developing mitigation strategies to improve heat tolerance and animal welfare. Therefore, we aimed to identify quantitative trait loci (QTL) regions associated with three physiological indicators of heat stress response in Holstein cattle, including rectal temperature (RT), respiration rate score (RS), and drooling score (DS). We estimated genetic parameters for all three traits. Subsequently, a weighted single-step genome-wide association study (WssGWAS) was performed based on 3200 genotypes, 151,486 phenotypic records, and 38,101 animals in the pedigree file. The candidate genes located within the identified QTL regions were further investigated through RNA sequencing (RNA-seq) analyses of blood samples for four cows collected in April (non-heat stress group) and four cows collected in July (heat stress group). RESULTS: The heritability estimates for RT, RS, and DS were 0.06, 0.04, and 0.03, respectively. Fourteen, 19, and 20 genomic regions explained 2.94%, 3.74%, and 4.01% of the total additive genetic variance of RT, RS, and DS, respectively. Most of these genomic regions are located in the Bos taurus autosome (BTA) BTA3, BTA6, BTA8, BTA12, BTA14, BTA21, and BTA24. No genomic regions overlapped between the three indicators of heat stress, indicating the polygenic nature of heat tolerance and the complementary mechanisms involved in heat stress response. For the RNA-seq analyses, 2627 genes were significantly upregulated and 369 downregulated in the heat stress group in comparison to the control group. When integrating the WssGWAS, RNA-seq results, and existing literature, the key candidate genes associated with physiological indicators of heat stress in Holstein cattle are: PMAIP1, SBK1, TMEM33, GATB, CHORDC1, RTN4IP1, and BTBD7. CONCLUSIONS: Physiological indicators of heat stress are heritable and can be improved through direct selection. Fifty-three QTL regions associated with heat stress indicators confirm the polygenic nature and complex genetic determinism of heat tolerance in dairy cattle. The identified candidate genes will contribute for optimizing genomic evaluation models by assigning higher weights to genetic markers located in these regions as well as to the design of SNP panels containing polymorphisms located within these candidate genes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40104-022-00748-6.
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spelling pubmed-93922502022-08-21 Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle Luo, Hanpeng Hu, Lirong Brito, Luiz F. Dou, Jinhuan Sammad, Abdul Chang, Yao Ma, Longgang Guo, Gang Liu, Lin Zhai, Liwei Xu, Qing Wang, Yachun J Anim Sci Biotechnol Research BACKGROUND: The study of molecular processes regulating heat stress response in dairy cattle is paramount for developing mitigation strategies to improve heat tolerance and animal welfare. Therefore, we aimed to identify quantitative trait loci (QTL) regions associated with three physiological indicators of heat stress response in Holstein cattle, including rectal temperature (RT), respiration rate score (RS), and drooling score (DS). We estimated genetic parameters for all three traits. Subsequently, a weighted single-step genome-wide association study (WssGWAS) was performed based on 3200 genotypes, 151,486 phenotypic records, and 38,101 animals in the pedigree file. The candidate genes located within the identified QTL regions were further investigated through RNA sequencing (RNA-seq) analyses of blood samples for four cows collected in April (non-heat stress group) and four cows collected in July (heat stress group). RESULTS: The heritability estimates for RT, RS, and DS were 0.06, 0.04, and 0.03, respectively. Fourteen, 19, and 20 genomic regions explained 2.94%, 3.74%, and 4.01% of the total additive genetic variance of RT, RS, and DS, respectively. Most of these genomic regions are located in the Bos taurus autosome (BTA) BTA3, BTA6, BTA8, BTA12, BTA14, BTA21, and BTA24. No genomic regions overlapped between the three indicators of heat stress, indicating the polygenic nature of heat tolerance and the complementary mechanisms involved in heat stress response. For the RNA-seq analyses, 2627 genes were significantly upregulated and 369 downregulated in the heat stress group in comparison to the control group. When integrating the WssGWAS, RNA-seq results, and existing literature, the key candidate genes associated with physiological indicators of heat stress in Holstein cattle are: PMAIP1, SBK1, TMEM33, GATB, CHORDC1, RTN4IP1, and BTBD7. CONCLUSIONS: Physiological indicators of heat stress are heritable and can be improved through direct selection. Fifty-three QTL regions associated with heat stress indicators confirm the polygenic nature and complex genetic determinism of heat tolerance in dairy cattle. The identified candidate genes will contribute for optimizing genomic evaluation models by assigning higher weights to genetic markers located in these regions as well as to the design of SNP panels containing polymorphisms located within these candidate genes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40104-022-00748-6. BioMed Central 2022-08-20 /pmc/articles/PMC9392250/ /pubmed/35986427 http://dx.doi.org/10.1186/s40104-022-00748-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Luo, Hanpeng
Hu, Lirong
Brito, Luiz F.
Dou, Jinhuan
Sammad, Abdul
Chang, Yao
Ma, Longgang
Guo, Gang
Liu, Lin
Zhai, Liwei
Xu, Qing
Wang, Yachun
Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title_full Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title_fullStr Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title_full_unstemmed Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title_short Weighted single-step GWAS and RNA sequencing reveals key candidate genes associated with physiological indicators of heat stress in Holstein cattle
title_sort weighted single-step gwas and rna sequencing reveals key candidate genes associated with physiological indicators of heat stress in holstein cattle
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392250/
https://www.ncbi.nlm.nih.gov/pubmed/35986427
http://dx.doi.org/10.1186/s40104-022-00748-6
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