Genome-wide association studies and functional annotation of pre-weaning calf mortality and reproductive traits in Nellore cattle from experimental selection lines

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Rodrigues, Gustavo R. D. ; Brito, Luiz F. ; Mota, Lucio F. M. ; Cyrillo, Joslaine N. S. G. ; Valente, Julia P. S. ; Benfica, Lorena F. ; Neto, Joao B. Silva ; Borges, Marcelo S. ; Monteiro, Fabio M. ; El Faro, Lenira ; Albuquerque, Lucia G. ; Mercadante, Maria E. Z.

• Document type: Journal article
• Source: BMC Genomics; v. 25, n. 1, p. 17-pg., 2024-12-18.

Abstract

BackgroundReproductive efficiency is crucial for the long-term economic sustainability of beef cattle production. Pregnancy loss and stillbirth are complex reproductive traits that do not yet have their genomic background fully understood, especially in zebu breeds (Bos taurus indicus). Hence, this study aimed to perform a genome-wide association study (GWAS) and functional annotation for conception success (CS), pregnancy loss (PL), stillbirth (SB), and pre-weaning calf mortality (PWM) in Nellore cattle. In this study, 3,728 cows with 17,094 reproductive records and 11,785 calves were evaluated. A total of 3,351 genotyped animals and 383,739 SNP markers were considered for GWAS analyses. SNP effects were estimated using the weighted single-step GWAS (WssGWAS), which considered two iterations. The top ten genomic windows with the highest contribution to the additive genetic variance of the traits were selected for gene annotation. Candidate genes were then analyzed for Gene Ontology terms (GO) and metabolic pathways.ResultsThe top ten genomic windows that explained the largest proportion of the direct additive genetic variance (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:{{\sigma\:}}_{\text{a}}<^>{2}$$\end{document}) for CS, PL, SB, and PWM accounted for 17.03% (overlapping with 79 genes), 16.76% (57 genes), 11.71% (73 genes), and 12.03% (65 genes) of the total \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\:{{\sigma\:}}_{\text{a}}<^>{2}$$\end{document}, respectively. For CS, significant GO terms included Somitogenesis (GO:0001756), Somite Development (GO:0061053), and Chromosome Segregation (GO:0007059). Considering PL, the processes annotated were the Regulation of Hormone Secretion (GO:0046883), and Hormone Transport (GO:0009914), along with the Glucagon Signaling Pathway (bta04922). Embryonic Development (GO:0045995), and Cerebellum Development (GO:0021549) were the main biological processes found in the gene enrichment analysis for SB. For PWM, the Regulation of Glucose metabolic processes (GO:0010906), Zinc Ion Homeostasis (GO:0055069), Lactation (GO:0007595), and Regulation of Insulin Secretion (GO:0050796) were the most significant GO terms observed.ConclusionsThese findings provide valuable information on genomic regions, candidate genes, biological processes, and metabolic pathways that may significantly influence the expression of complex reproductive traits in Nellore cattle, offering potential contributions to breeding strategies and future genomic selection strategies. (AU)

• FAPESP's process: 24/01909-7 - Genome scan for transmission ratio distortion regions and its associations with abortion, stillbirth and pre-weaning mortality in Nellore cattle
• Grantee: Gustavo Roberto Dias Rodrigues
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 24/05697-4 - Study of the indirect genetic effect of social interaction on traits obtained in feed efficiency tests of Nellore cattle
• Grantee: Júlia de Paula Soares Valente
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/10630-2 - Genetic aspects of meat production quality, efficiency and sustainability in Nelore breed animals
• Grantee: Lucia Galvão de Albuquerque
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/11176-4 - Mapping candidates for lethal haplotypes and genomic regions associated with the occurrence of abortion and pre-weaning mortality in Nellore cattle
• Grantee: Gustavo Roberto Dias Rodrigues
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 22/11852-7 - Structural equation modeling as a tool to interpret genotype-environment interaction and genome-wide association (GWAS) for growth and reproductive traits in Nellore heifers using whole-genome sequence data
• Grantee: Lúcio Flávio Macedo Mota
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/50339-5 - Institutional research development plan of the Animal Science Institute (PDIp)
• Grantee: Lenira El Faro Zadra
• Support Opportunities: Research Grants - State Research Institutes Modernization Program