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United States Department of Agriculture

Agricultural Research Service

Research Project: IDENTIFICATION OF HOST IMMUNE FACTORS AND INTERVENTION STRATEGIES FOR MASTITIS Title: A genome-wide association study identified CYP2J2 as a major gene controlling serum vitamin D in beef cattle

Authors
item CASAS, EDUARDO
item Leach, Richard
item REINHARDT, TIMOTHY
item THALLMAN, RICHARD
item LIPPOLIS, JOHN
item BENNETT, GARY
item KUEHN, LARRY

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 6, 2013
Publication Date: August 1, 2013
Repository URL: http://http;//handle.nal.usda.gov/10113/57378
Citation: Casas, E., Leach, R.J., Reinhardt, T.A., Thallman, R.M., Lippolis, J.D., Bennett, G.L., Kuehn, L.A. 2013. A genome-wide association study identified CYP2J2 as a major gene controlling serum vitamin D in beef cattle. Journal of Animal Science. 91:3549-3556.

Interpretive Summary: Vitamin D is an important modulator of calcium homeostasis and has several effects on the immune system. The objective of this study was to establish if vitamin D status in cattle had a genetic component, and to establish where in the genetic material (genome) were the genes influencing the production of vitamin D. It was established that vitamin D status has a moderate to high genetic component (heritability). A region in bovine chromosome 3 was detected as harboring a gene influencing levels of vitamin D in cattle. Within this region of bovine chromosome 3, the gene CYP2J2 was identified. Results from this study indicate that CYP2J2 is a major gene controlling the synthesis of vitamin D to the active form of the hormone, and it should be considered a prime candidate gene for understanding genetic and physiological factors affecting vitamin D status. Vitamin D status influence the development of a robust immune response therefore it plays an important role and contributes to cattle health.

Technical Abstract: Vitamin D is an important modulator of calcium homeostasis and has several eefects on the immune system. The objective of the study was to estimate its heritability, and to identify genomic regions associated with concentration of circulating 25-hydroxyvitamin D (25OHD) in beef cattle. Status of vitamin D was measured in crossbred animals from the Cycle VII of the USMARC Germplasm Evaluation Project. Progeny were born from March through May in 2008 and in 2010. Heritability was estimated and a Genome-wide Association Study was conducted on the concentration of 25OHD measured in 1,432 animals at pre-conditioning and 1,333 animals at weaning. Genotyping of the population was done by imputing from the parental generation genotyped with a high density array (777,000 SNP) to a target population genotyped with a medium density SNP array (50,000 SNP). After imputation, 675,018 SNP were used in the GWAS analysis. Heritability of concentration of circulating 25OHD in cattle at pre-conditioning and at weaning was 0.41± 0.08 and 0.32 ± 0.11, respectively. A region on chromosome 3 was associated with circulating 25OHD. The region on BTA3 had 7 SNP significantly (P< 7.4 x 10-8) associated at the genome-wide level with serum concentrations of serum 25OHD. Genome-wide significant SNP spanned the region between 84.93 megabases (MB) and 86.65 MB; however, 6 SNP reside between 86.64 and 86.65 MB. The gene CYP2J2 was identified as a candidate gene associated with concentrations of serum 25OHD in cattle. This is one of 6 enzymes involved in metabolizing vitamin D to 25OHD. Results from the present study suggest that CYP2J2 is a major gene controlling serum 25OHD levels in cattle. CYP2J2 should be considered a prime candidate for understanding both genetic and physiological factors affecting serum 25OHD concentrations in cattle, therefore, vitamin D status.

Last Modified: 9/10/2014