An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens
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 tr...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | deu |
| Published: |
BMC
2020-02-01
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| Series: | Genetics Selection Evolution |
| Online Access: | http://link.springer.com/article/10.1186/s12711-020-00532-y |
| _version_ | 1818447304893399040 |
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| author | Dirk-Jan De Koning Nazaret Dominguez-Gasca Robert H. Fleming Andrew Gill Dominic Kurian Andrew Law Heather A. McCormack David Morrice Estefania Sanchez-Rodriguez Alejandro B. Rodriguez-Navarro Rudolf Preisinger Matthias Schmutz Veronica Šmídová Frances Turner Peter W. Wilson Rongyan Zhou Ian C. Dunn |
| author_facet | Dirk-Jan De Koning Nazaret Dominguez-Gasca Robert H. Fleming Andrew Gill Dominic Kurian Andrew Law Heather A. McCormack David Morrice Estefania Sanchez-Rodriguez Alejandro B. Rodriguez-Navarro Rudolf Preisinger Matthias Schmutz Veronica Šmídová Frances Turner Peter W. Wilson Rongyan Zhou Ian C. Dunn |
| author_sort | Dirk-Jan De Koning |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T20:01:30Z |
| format | Article |
| id | doaj.art-338b0c9d7bc84c469cfdbb2662a1f510 |
| institution | Directory Open Access Journal |
| issn | 1297-9686 |
| language | deu |
| last_indexed | 2024-12-14T20:01:30Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Genetics Selection Evolution |
| spelling | doaj.art-338b0c9d7bc84c469cfdbb2662a1f5102022-12-21T22:49:08ZdeuBMCGenetics Selection Evolution1297-96862020-02-0152111710.1186/s12711-020-00532-yAn eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hensDirk-Jan De Koning0Nazaret Dominguez-Gasca1Robert H. Fleming2Andrew Gill3Dominic Kurian4Andrew Law5Heather A. McCormack6David Morrice7Estefania Sanchez-Rodriguez8Alejandro B. Rodriguez-Navarro9Rudolf Preisinger10Matthias Schmutz11Veronica Šmídová12Frances Turner13Peter W. Wilson14Rongyan Zhou15Ian C. Dunn16Swedish University of Agricultural SciencesDepartamento de Mineralogía y Petrologia, Universidad de GranadaThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghDepartamento de Mineralogía y Petrologia, Universidad de GranadaDepartamento de Mineralogía y Petrologia, Universidad de GranadaLohmann TierzuchtLohmann TierzuchtThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghThe Roslin Institute, University of EdinburghAbstract 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.http://link.springer.com/article/10.1186/s12711-020-00532-y |
| spellingShingle | Dirk-Jan De Koning Nazaret Dominguez-Gasca Robert H. Fleming Andrew Gill Dominic Kurian Andrew Law Heather A. McCormack David Morrice Estefania Sanchez-Rodriguez Alejandro B. Rodriguez-Navarro Rudolf Preisinger Matthias Schmutz Veronica Šmídová Frances Turner Peter W. Wilson Rongyan Zhou Ian C. Dunn An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens Genetics Selection Evolution |
| title | An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| title_full | An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| title_fullStr | An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| title_full_unstemmed | An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| title_short | An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| title_sort | eqtl in the cystathionine beta synthase gene is linked to osteoporosis in laying hens |
| url | http://link.springer.com/article/10.1186/s12711-020-00532-y |
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