No abstract

Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: AJ271386), encoding the β-carotene 15, 15′-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A.

This article is available online at http://www.jlr.org "methyl-end" FA desaturases. Therefore, linoleic acid and ␣ -linolenic acid must be provided by the diet ( 3 ). These dietary essential FAs then serve as precursors for longer PUFAs of the n-6 and n-3 series, including arachidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3) required for many important physiological functions in humans ( 4,5 ). In this PUFA biosynthesis, only "front-end" desaturases ( ⌬ 5-and ⌬ 6-desaturases) are involved to introduce new double bonds between the preexisting double bonds and the carboxyl end of FAs ( 6 ).In 2000, the genomic structure of the fatty acid desaturase (FADS) cluster, located on chromosome 11 in humans, was reported ( 7 ). This cluster includes the FADS1 and FADS2 genes that code, respectively, for the well-known ⌬ 5-and ⌬ 6-desaturases involved in PUFA biosynthesis ( 8-10 ). A third gene was identifi ed on this cluster with high degree of nucleotide sequence homology with both FADS1 (62%) and FADS2 (70%) and was therefore named FADS3. Since its fi rst description in humans ( 7 ), FADS3 has been identifi ed in rats ( 11 ), baboons ( 12 ), mice ( 3 ), and many other mammals showing a similar nucleotide sequence and intron/exon organization ( 12 ). When analyzing the peptide sequence deduced from the FADS3 nucleotide sequence, FADS3 protein was identifi ed as a putative desaturase, according to its similarity with FADS1 and FADS2. Indeed, the predicted structure of FADS3 is composed of an N-terminal cytochrome b5-like domain characterized by a HPGG motif shown to be essential for the ⌬ 6-desaturase activity of FADS2 ( 13 ) QIEHH in the rat) characteristic of front-end-desaturases ( 14 ). According to its amino acid sequence, FADS3 was thereafter supposed to Abstract Fatty acid desaturases play critical roles in regulating the biosynthesis of unsaturated fatty acids in all biological kingdoms. As opposed to plants, mammals are so far characterized by the absence of desaturases introducing additional double bonds at the methyl-end site of fatty acids. However, the function of the mammalian fatty acid desaturase 3 (FADS3) gene remains unknown. This gene is located within the FADS cluster and presents a high nucleotide sequence homology with FADS1 ( ⌬ 5-desaturase) and FADS2 ( ⌬ 6-desaturase). Here, we show that rat FADS3 displays no common ⌬ 5-, ⌬ 6-or ⌬ 9-desaturase activity but is able to catalyze the unexpected ⌬ 13-desaturation of trans -vaccenate. Although there is no standard for complete conclusive identifi cation, structural characterization strongly suggests that the ⌬ 11,13-conjugated linoleic acid (CLA) produced by FADS3 from trans -vaccenate is the trans 11, cis 13-CLA isomer. In rat hepatocytes, knockdown of FADS3 expression specifically reduces trans -vaccenate ⌬ 13-desaturation. Evidence is presented that FADS3 is the fi rst "methyl-end" fatty acid desaturase functionally characterized in mammals. FA desaturases introduce double bonds between defi ned carbons of the fatty acyl chain and catalyze ...