Genes for stronger bones mapped in White Leghorn laying hens

Scientists have mapped the genetic architecture of bone strength and composition in White Leghorn laying hens, identifying a chromosome 20 region significantly associated with humeral stiffness that overlaps with humeral breaking strength and tibial cortical thickness. The markers, located between 11.55 and 12.29 megabases on chromosome 20 and in strong linkage disequilibrium with one another, sit within a previously identified quantitative trait locus for bone biomechanical strength and body weight. That region harbors the bone morphogenetic protein 7 gene, BMP7, which has a known role in skeletogenesis and growth in chickens.

Body mass recorded at 70 weeks averaged 1716.66 grams with a standard deviation of 127.68 grams.

Thirteen SNPs passed the genome-wide significance threshold, all on chromosome 20 between 11.59 and 11.78 megabases with minor allele frequencies of 0.4 to 0.5, associated with humerus stiffness. A single SNP on chromosome 5 was associated with humerus density, and three SNPs on chromosome 1 were associated with tibia stiffness, though the latter three were later judged spurious because of their very low minor allele frequency of 0.007, their physical isolation from other SNPs, and their lack of support from neighboring markers in linkage disequilibrium. No SNP reached significance for the other traits analyzed. Suggestive associations, however, were widespread: markers above the suggestive threshold appeared across 20 chromosomes for mechanical and density phenotypes, with chromosome 5 containing suggestive SNPs for six of the ten phenotypes.

Among overlapping signals, the highest number of shared SNPs, 34, fell within the large chromosome 20 region for humerus breaking strength, stiffness, and tibial cortical thickness. The top significant SNP at position 11,715,985 base pairs was in strong linkage disequilibrium, with r-squared values above 0.8, with 13 nearby SNPs. Individuals carrying the G/G genotype at that SNP showed humeri breaking strength 6 to 16 percent higher, stiffness 11 to 21 percent higher, and cortical thickness 4 to 9 percent higher compared with A/G or A/A genotypes. When the statistical model adjusted for body weight, the significant signals dropped below the threshold, while associations strengthened significantly in the unadjusted model. The authors interpret the two models as addressing different biological questions: the unadjusted analysis captures total association including effects shared with or mediated through body weight, whereas the adjusted analysis evaluates associations independently of body weight. The moderate genetic correlation between body weight and humeral breaking strength, 0.39 with a standard error of 0.14, indicates part of the association arises from shared genetic background affecting growth and skeletal robustness.

A second region of interest emerged on chromosome 1 between 173.5 and 173.6 megabases, where seven overlapping suggestive SNPs were associated with medullary organic content, mineral content, and the total amount of carbonate in bone mineral measured by FTIR. These SNPs were in high linkage disequilibrium with the top SNP at position 173,634,193 but showed lower correlation with surrounding markers. Relatively common in the population with a minor allele frequency of 0.23, the markers showed genotype-dependent effects: individuals with the A/A genotype had 6 to 13 percent higher thermogravimetric mineral content and 8 to 16 percent higher FTIR mineral carbonate content, but 5 to 10 percent lower organic content, compared with A/G and G/G genotypes. The opposing effects on organic and mineral content suggest this region may influence the relative balance between the mineral and organic components of medullary bone.

The chromosome 1 region contains the long non-coding RNA LOC107052041, nicknamed LncFAM, which has previously been mapped within growth-related quantitative trait loci, and whose polymorphisms have been associated with body weight and skeletal dimensions in chickens. The gene has been proposed to regulate its target gene SUPT20H, which was also detected within this quantitative trait locus and is required for normal axial skeletal development in mice. Adjustment for body weight decreased the strength of the association signal with medullary mineral and organic contents, suggesting the associations may partly reflect shared genetic effects on body weight and medullary bone composition. The region also harbors ALG5, involved in glycosylation and regulation of cell functions in the bone marrow micro-environment, and SMAD9, which plays a role in bone morphogenetic protein signaling and is crucial for bone development and maintenance in mammalian studies.

Heritability estimates reinforced the compositional findings. For bone mechanical and density parameters in the tibia, heritabilities ranged from 0.10 to 0.33, with tibia density the most heritable trait. Humeri estimates ranged between 0.10 and 0.29, with stiffness most heritable, and keel radiographic density showed low heritability of 0.08. Thermogravimetry traits yielded higher heritabilities, from 0.01 to 0.19, than infrared spectroscopy traits, which ranged from 0.001 to 0.12. Medullary organic and mineral contents were the most heritable compositional traits at approximately 0.19, and both were strongly genetically correlated with tibia density, at 0.72 for mineral and minus 0.7 for organic content, indicating that higher mineral content in medullary bone accompanies improved density. The genetic correlation between medullary mineral and organic contents was strongly negative, near minus 0.9, reflecting the inherent balance between these matrices in bone.

The authors note that cortical compositional traits showed no significant genome-wide associations, with low heritability below 0.09 limiting the power to detect variants of small effect in a population of roughly 900 birds. Several FTIR traits with near-zero heritability produced exceptionally high genetic correlations with tibia density, up to 0.99, but the researchers caution these estimates should be questioned because genetic correlations involving traits with almost no heritable variation may be estimated incorrectly. Keel bone density showed low heritability and no significant markers, aligning with earlier pedigree-based data and suggesting alternative phenotyping approaches are needed. The study identified 255 unique genes within 100 kilobases of candidate markers, of which 69 were reported by the DAVID tool as involved in eight significant biological processes. The authors conclude that the two candidate genomic regions, one with a significant effect on bone strength and one with a suggestive effect on composition, provide candidates for functional validation and for future evaluation of their potential to improve the prediction of bone strength in laying hens.

Subject of Research: Genome-wide association study of bone strength and composition traits in White Leghorn laying hens

Article Title: Genetic architecture of bone strength and composition in White Leghorn laying hens

Article References: Kurta, K., Wilson, P. W., Andersson, B., Schmutz, M., Cavero, D., Enrich-Essvein, T., Crespo-Lopez, L., Rodriguez-Navarro, A. B., Dunn, I. C., de Koning, D.-J., & Johnsson, M. (2026). Genetic architecture of bone strength and composition in White Leghorn laying hens. Genetics Selection Evolution, 58(1), Article 80. https://doi.org/10.1186/s12711-026-01103-3

Image Credits: AI Generated

DOI: 10.1186/s12711-026-01103-3

Keywords: laying hens, bone strength, bone composition, GWAS, White Leghorn, BMP7, medullary bone, heritability, keel bone, poultry genetics, tibia, humerus