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Research article - Peer-reviewed, 2020

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens

De Koning, Dirk-Jan; Dominguez-Gasca, Nazaret; Fleming, Robert H.; Gill, Andrew; Kurian, Dominic; Law, Andrew; McCormack, Heather A.; Morrice, David; Sanchez-Rodriguez, Estefania; Rodriguez-Navarro, Alejandro B.; Preisinger, Rudolf; Schmutz, Matthias; Smidova, Veronica; Turner, Frances; Wilson, Peter W.; Zhou, Rongyan; Dunn, Ian C.

Abstract

Background Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. Results Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. Conclusions Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine.

Keywords

laying hens; poultry; skeletal damage; bone fractures; selective breeding

Published in

Genetics Selection Evolution
2020, volume: 52, number: 1, article number: 13
Publisher: BMC

Authors' information

Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics
Dominguez-Gasca, Nazaret
Univ Granada
Fleming, Robert H.
Univ Edinburgh
Gill, Andrew
Univ Edinburgh
Kurian, Dominic
Univ Edinburgh
Law, Andrew
Univ Edinburgh
McCormack, Heather A.
Univ Edinburgh
Morrice, David
Univ Edinburgh
Sanchez-Rodriguez, Estefania
Univ Granada
Rodriguez-Navarro, Alejandro B.
Univ Granada
Preisinger, Rudolf
Lohmann Tierzucht
Schmutz, Matthias
Lohmann Tierzucht
Smidova, Veronica
Univ Edinburgh
Turner, Frances
Univ Edinburgh
Wilson, Peter W.
Univ Edinburgh
Zhou, Rongyan
Univ Edinburgh
Dunn, Ian C.
Univ Edinburgh

UKÄ Subject classification

Animal and Dairy Science

Publication Identifiers

DOI: https://doi.org/10.1186/s12711-020-00532-y

URI (permanent link to this page)

https://res.slu.se/id/publ/105223