A nonsense mutation in the beta-carotene oxygenase 2 (BCO2) gene is tightly associated with accumulation of carotenoids in adipose tissue in sheep (Ovis aries)

Abstract

BackgroundSheep carcasses with yellow fat are sporadically observed at Norwegian slaughter houses. This phenomenon is known to be inherited as a recessive trait, and is caused by accumulation of carotenoids in adipose tissue. Two enzymes are known to be important in carotenoid degradation in mammals, and are therefore potential candidate genes for this trait. These are beta-carotene 15,15'-monooxygenase 1 (BCMO1) and the beta-carotene oxygenase 2 (BCO2).ResultsIn the present study the coding region of the BCMO1 and the BCO2 gene were sequenced in yellow fat individuals and compared to the corresponding sequences from control animals with white fat. In the yellow fat individuals a nonsense mutation was found in BCO2 nucleotide position 196 (c.196C>T), introducing a stop codon in amino acid position 66. The full length protein consists of 575 amino acids. In spite of a very low frequency of this mutation in the Norwegian AI-ram population, 16 out of 18 yellow fat lambs were found to be homozygous for this mutation.ConclusionIn the present study a nonsense mutation (c.196C>T) in the beta-carotene oxygenase 2 (BCO2) gene is found to strongly associate with the yellow fat phenotype in sheep. The existence of individuals lacking this mutation, but still demonstrating yellow fat, suggests that additional mutations may cause a similar phenotype in this population. The results demonstrate a quantitatively important role for BCO2 in carotenoid degradation, which might indicate a broad enzyme specificity for carotenoids. Animals homozygous for the mutation are not reported to suffer from any negative health or development traits, pointing towards a minor role of BCO2 in vitamin A formation. Genotyping AI rams for c.196C>T can now be actively used in selection against the yellow fat trait.

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

“…These enzymes play an important role in carotenoid homeostasis of blood and tissues, as seen by genetic variability in the corresponding genes in humans and animals (35)(36)(37)(38)(39). However, little is known as to whether an additional mechanism exists in cells to chemically modify these lipids.…”

Inactivity of human β,β-carotene-9′,10′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment

“…Although these proteins may be required for the uptake and stabilization of these compounds in the human retina, they are not sufficient to explain why xanthophylls are not found in other mammalian retinas, because these binding proteins are often found in these animals' retinas, too. Recent investigations on various mammalian BCO2 enzymes have shown that BCO2 can generally cleave xanthophylls such as lutein and zeaxanthin, and BCO2 mutations can cause the tissues of chickens, cows, and sheep to develop a deep yellow color due to carotenoid deposition (13)(14)(15)(16)(17). To explain the unique deposition of xanthophyll carotenoids in the primate retina, we hypothesized that either human BCO2 is not expressed in human retina, or it is an inactive carotenoid cleavage enzyme.…”

“…Its physiological function is supported by genetic evidence from several species. A nonsense mutation in the sheep BCO2 gene that introduces a stop codon at amino acid 66 of the 575-aa full-length protein is strongly associated with a yellow fat phenotype due to the high amount of lutein that deposits in tissue (15). Cis-acting and tissue-specific regulatory mutations that inhibit the expression of BCO2 in domestic chickens can cause them to have yellow skin secondary to carotenoid accumulation (16).…”

The Identification of SNPs in BCDO2 Gene for Skin Color in Chinese Indigenous Chicken

“…A nonsense mutation (c.196C>T) of the BCDO2 gene was also found to be strongly associated with yellow fat in sheep (Våge DI & Boman IA, 2010).…”