Two CYP17 genes in the South African Angora goat (Capra hircus) - the identification of three genotypes that differ in copy number and steroidogenic output

In mammals, cytochrome P450 17alpha-hydroxylase/17-20 lyase (CYP17), which is encoded by a single gene, plays a critical role in the production of mineralocorticoids, glucocorticoids and androgens by the adrenal cortex. Two CYP17 isoforms with unique catalytic properties have been identified in the South African Angora goat (Capra hircus), a subspecies that is susceptible to cold stress because of the inability of the adrenal cortex to produce sufficient levels of cortisol. A real-time-based genotyping assay was used in this study to identify the distribution of the two CYP17 alleles in the South African Angora population. These data revealed that the two CYP17 isoforms were not the product of two alleles of the same gene, but two separate CYP17 genes encoding the two unique CYP17 isoforms. This novel finding was subsequently confirmed by quantitative real-time PCR. Goats were divided into three unique genotypes which differed not only in the genes encoding CYP17, but also in copy number. Furthermore, in vivo assays revealed that the identified genotypes differed in their ability to produce cortisol in response to intravenous insulin injection. This study clearly demonstrates the presence of two CYP17 genes in the South African Angora goat, and further implicates CYP17 as the primary cause of the observed hypocortisolism in this subspecies.