ORIGINAL RESEARCH article
Front. Anim. Sci.
Sec. Animal Breeding and Genetics
This article is part of the Research TopicExploring the Intersection of Animal Breeding, Genetics, and Genomics in Modern AgricultureView all 8 articles
Bovine respiratory disease-associated ultrasonographic lung lesions in Holstein calves: a genomic perspective on Copy Number Variants and Homozygosity
Provisionally accepted
Francesca Bernini
Antonio Boccardo
Andrea Delledonne
Valerio Bronzo
Giacomo Lanfredi
Alessandro Bagnato
Maria Giuseppina Strillacci*- University of Milan, Milan, Italy
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Bovine Respiratory Disease (BRD) represents a major health and economic challenge in cattle farming especially affecting young calves. Although previous SNP-based genome-wide association studies (GWAS) have identified candidate loci linked to BRD susceptibility, they only explain a fraction of the trait's heritability. Using genotypes from a previous study that employed a selective genotyping approach, we analyzed Holstein calves classified as BRD-resistant or BRD-susceptible, based on thoracic ultrasonography and clinical scoring. In particular, structural variations, specifically copy number variants (CNVs) and runs of homozygosity (ROH), were investigated due to their emerging role as complementary genomic features potentially involved in disease resistance. A total of 2,666 CNVs were identified, and the CNV-GWAS revealed 10 significant CNV regions (CNVRs), encompassing or near 15 candidate genes. While the ROH analysis identified 8,226 segments we further applied a fixed-window approach to compare ROH frequencies between groups revealing 19 regions with significantly different ROH frequencies. Gene annotation of both CNVRs and differential ROH windows uncovered genes linked to immune response, lung development, and known BRD-associated pathways. Functional enrichment analyses using DAVID and Cytoscape-GeneMANIA indicated involvement of antiviral responses, GPCR signaling, calcium signaling, and estrogen receptor pathway in disease resistance. Notably, 37% of the genes identified in this study overlapped with those reported in previous BRD-related studies. This integrative genomic analysis highlights the relevance of structural variation in shaping BRD resistance and susceptibility in dairy calves. By integrating CNV mapping, ROH analysis, and functional annotation approaches, we identified novel and previously reported candidate genes potentially involved in innate immune processes. These findings support the implementation of precision breeding strategies aimed at improving disease resilience in cattle.
Keywords: copy number variant, Run of Homozigosity, bovine respiratory disease, Holstein calves, BRD genetic resistance
Received: 07 Sep 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Bernini, Boccardo, Delledonne, Bronzo, Lanfredi, Bagnato and Strillacci. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Maria Giuseppina Strillacci, maria.strillacci@unimi.it
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