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United States Department of Agriculture

Agricultural Research Service

Title: A VARIANT OF PORCINE THYROXINE-BINDING GLOBULIN HAS REDUCED AFFINITY FOR THYROXINE AND IS ASSOCIATED WITH TESTIS SIZE

Authors
item Nonneman, Danny
item Rohrer, Gary
item Wise, Thomas
item Lunstra, Donald
item Ford, Johny

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 10, 2004
Publication Date: January 3, 2005
Citation: Nonneman, D.J., Rohrer, G.A., Wise, T.H., Lunstra, D.D., Ford, J.J. 2005. A variant of porcine thyroxine-binding globulin has reduced affinity for thyroxine and is associated with testis size. Biology of Reproduction. 72:214-220.

Interpretive Summary: Meishan boars have dramatically higher levels of circulating gonadotropins and smaller testes compared to conventional breeds. Testicular sperm production is positively related to testis size, and in an industry with a growing use of artificial insemination for production, the culling of boars because of reduced reproductive success is of economic concern. Quantitative trait loci (QTL) for testis size, plasma FSH in boars, and body composition (backfat) have been identified near the centromere of the porcine X chromosome. Since thyroid function affects Sertoli cell development and adult testis size in rodents, and thyroxine-binding globulin (TBG) maps to this region on the porcine X chromosome, TBG is a positional candidate gene for testis size. We discovered a polymorphism in the porcine thyroxine-binding globulin (TBG) gene that results in an amino acid change of the consensus histidine to an asparagine. This SNP resides in the ligand-binding domain of the mature polypeptide and the Meishan allele is the conserved allele found in human, bovine, sheep and rodent TBG. Binding studies indicate that the asparagine (White Composite) isoform has significantly greater binding affinity for thyroxine than the histidine (Meishan) isoform. Alternate alleles in F10 boars from the resource population are significantly associated with testis weight. Therefore, this polymorphism in TBG is a candidate for the causative variation affecting testis size in boars.

Technical Abstract: The field of genomics applies the dissection of genetic differences towards an understanding of the biology of complex traits. Quantitative trait loci (QTL) for testis size, plasma FSH in boars, and body composition (backfat) have been identified near the centromere on the X chromosome in a Meishan-White Composite resource population. Since thyroid function affects Sertoli cell development and adult testis size in rodents, and thyroxine-binding globulin (TBG) maps to this region on the porcine X chromosome, TBG was a positional candidate gene for testis size. We discovered a polymorphism in exon 2 of the porcine TBG gene that results in an amino acid change of the consensus histidine to an asparagine. This SNP resides in the ligand-binding domain of the mature polypeptide and the Meishan allele is the conserved allele found in human, bovine, sheep and rodent TBG. Binding studies indicate altered binding characteristics of the allelic variants of TBG with the asparagine (White Composite) isoform having significantly greater affinity for thyroxine than the histidine (Meishan) isoform. Alternate alleles in boars from the resource population are also significantly associated with testis weight. Therefore, this polymorphism in TBG is a candidate for the causative variation affecting testis size in boars.

Last Modified: 9/1/2014