An Italian research team has mapped dozens of genomic regions linked to the traits that decide whether a newborn dairy calf gets the antibodies it needs to survive its first hours of life. In a genome-wide association study of 960 genotyped Italian Holstein cows, significant markers for colostrum yield and immunoglobulin concentrations turned out to be scattered across the genome rather than concentrated in a few powerful genes, confirming that the cow’s capacity to produce ample, antibody-rich first milk is a highly polygenic characteristic. The study, published in Genetics Selection Evolution, also found that none of the detected signals sit in the famous genes that govern mature milk production, suggesting that colostrum formation runs on a largely separate genetic program.
The researchers framed their work around a concept they call colostrability: the cow’s ability to secrete at least 4 liters of colostrum containing at least 50 grams of immunoglobulin G per liter at calving. These thresholds matter because calves are born essentially agammaglobulinemic, with no antibodies of their own, and depend entirely on colostrum consumed at the first meal to acquire passive immunity. Failure of passive transfer occurs when a calf’s serum IgG does not reach 12 grams per liter within the first 12 hours of life, a situation that arises when the dam produces too little colostrum or colostrum that is too dilute.
To capture the phenotypes, the team relied on measurements taken within 6 hours of calving, with complete empty milking of the udder into a graduated bucket. Colostrum samples were frozen on the farm and later analyzed in the laboratory using near-infrared spectroscopy prediction models, whose external validation coefficients of determination were 0.82 for IgG concentration and 0.84 for total immunoglobulin concentration. Data came from 31 farms, with between 1 and 147 genotyped cows each, and unsupervised calvings were excluded to avoid biasing the records. After editing, the dataset included 296 cows in first parity, 232 in second, 174 in third, 109 in fourth, and 101 in fifth.
Genotypes were imputed to 86,339 markers across all 29 bovine autosomes, and quality control in PLINK 2.0 left 69,806 markers for analysis. A principal component analysis detected no subpopulations or genetic clustering among farms, and quantile-quantile plots showed no systematic bias in the association model. The GWAS itself used a linear mixed model in GCTA that accounted for herd-season and parity as fixed effects and included a genomic relationship matrix to control for population structure. Because Bonferroni correction ignores linkage disequilibrium between markers, the team applied a false discovery rate threshold of 0.20, a deliberately exploratory cut-off intended to flag genomic regions deserving future attention rather than to declare definitive causal variants.
The results painted a dispersed picture. For colostrum yield, significant SNPs appeared on chromosomes 3, 5, 10, 11, 21, and 22, with the two most significant markers falling within the genes GPHN on BTA10 and NOVA1 on BTA21. On BTA22, one marker sat within an annotated segment and flanked 22 genes, although part of the significant regions have functions that remain unclear. For IgG concentration, signals emerged on BTA1, 6, 7, 11, 19, 21, and 25, while total immunoglobulin concentration was associated with regions on BTA6, 7, 11, 21, 23, and 25. IgG yield, a composite trait calculated by multiplying volume by IgG concentration, showed the fewest significant markers, sharing only one SNP, BTB-01525804 on BTA21, with colostrum yield.
As expected from the strong phenotypic correlation between IgG and total immunoglobulin concentration, those two traits overlapped heavily in their significant signals, with most total-Ig SNPs also detected for IgG. In contrast, IgG yield showed limited overlap with either of its mathematical components despite their correlations, a pattern the authors attribute to the distinct polygenic architectures of the traits. Only a minority of significant SNPs were intragenic; most lay near candidate genes or in poorly characterized LOC segments. The most significant signal for IgG concentration flanked FOXG1 on BTA21, a transcription factor gene well known for its role in brain development and, when mutated, neurological disorders in several species including humans.
Several signals for both IgG and total immunoglobulin fell within or near the olfactory receptor 7 subfamily A cluster on BTA7, including an intragenic SNP in OR7A96. The authors caution that, given the exploratory design, this positional signal may simply reflect proximity to a clustered gene family rather than a genuine functional link, though olfactory receptors expressed in immune and epithelial cells are known to participate in signaling and pathogen recognition. Other flagged genes carry intriguing immune credentials: RASGEF1B has been implicated in macrophage gene regulation in response to bacterial endotoxin, and ENOPH1 was recently highlighted in a study of mastitis resistance in dairy cows.
An exploratory functional enrichment analysis added preliminary biological context. For colostrum yield, none of seven enriched terms passed a false discovery rate below 0.05, though mitochondrion-related genes and metabolic pathways dominated by gene count. IgG concentration yielded 23 gene ontology terms and three KEGG pathways, 11 of them significant, with membrane components, G protein-coupled receptor activity, and G protein-coupled receptor signaling pathways among the most heavily represented. Total immunoglobulin concentration showed a similar signaling-and-receptor profile. The authors interpret this as evidence that colostrum yield reflects more structural biology of the mammary gland, while antibody transfer into colostrum is strongly influenced by receptor-mediated processes, including epithelial receptor pathways such as those involving the epidermal growth factor receptor.
Notably, no significant SNPs or signal peaks appeared in the major well-known milk-production genes, including DGAT1, GHR, PRLR, ABCG2, the casein cluster, SCD1, FASN, and AGPAT6. The team concludes that the regions governing colostrogenesis and postpartum IgG concentration differ from those shaping the yield and composition of mature milk, meaning colostrability appears regulated by distinct biological domains largely independent of the genetic architecture of regular lactation. That distinction could matter for breeding programs, since selecting for higher milk production would not automatically improve a cow’s ability to nourish her calf immunologically.
The authors are careful about the limits of the work. The sample size of 960 cows remains limited, the false discovery threshold was intentionally permissive, and causality could not be verified; the shared U6 annotation across traits, for instance, is a common noncoding RNA segment that should not be treated as a candidate causal gene. Comparisons with earlier GWAS in Chinese Holsteins and Swedish dairy cattle show chromosome-level convergence on BTA6, BTA11, BTA21, and BTA22 for immunoglobulin-related traits, but no clear positional or candidate-gene replication, likely because previous studies often used refractive index as a proxy for quality rather than measured IgG, and sampling protocols differ widely. The team calls for larger, independent, and harmonized datasets with standardized sampling, and for future studies to integrate calf-side phenotypes such as intestinal IgG absorption capacity, gut permeability, early-life survival, and health outcomes, positioning colostrability as one promising component of a broader calf health index.
Subject of Research: Genomic regions associated with colostrum yield and immunoglobulin concentration in Italian Holstein cattle
Article Title: Genome-wide association study reveals key genomic regions underlying colostrability in Italian Holstein cattle
Article References: Costa, A., De Marchi, M., Vegni, J., Goi, A., Magro, S., Cassandro, M., Finocchiaro, R., Marusi, M., Benzoni, L., van Kaam, J.-T., Niero, G., & Visentin, G. (2026). Genome-wide association study reveals key genomic regions underlying colostrability in Italian Holstein cattle. Genetics Selection Evolution, 58(1), Article 54. https://doi.org/10.1186/s12711-026-01080-7
Image Credits: AI Generated
DOI: 10.1186/s12711-026-01080-7
Keywords: colostrum, Italian Holstein, genome-wide association study, immunoglobulin G, calf health, polygenic traits, dairy cattle genetics, failure of passive transfer, functional enrichment, mammary gland, BTA22, near-infrared spectroscopy
News Source: Juliet Wilcox. (October 29, 2026). Cow Colostrum Quality Traced to Scattered Genomic Regions Across the Bovine Genome. Scienmag.
