Polymorphism in the ELOVL6 Gene Is Associated with a Major QTL Effect on Fatty Acid Composition in Pigs

Abstract

BackgroundThe ELOVL fatty acid elongase 6 (ELOVL6), the only elongase related to de novo lipogenesis, catalyzes the rate-limiting step in the elongation cycle by controlling the fatty acid balance in mammals. It is located on pig chromosome 8 (SSC8) in a region where a QTL affecting palmitic, and palmitoleic acid composition was previously detected, using an Iberian x Landrace intercross. The main goal of this work was to fine-map the QTL and to evaluate the ELOVL6 gene as a positional candidate gene affecting the percentages of palmitic and palmitoleic fatty acids in pigs.Methodology and Principal FindingsThe combination of a haplotype-based approach and single-marker analysis allowed us to identify the main, associated interval for the QTL, in which the ELOVL6 gene was identified and selected as a positional candidate gene. A polymorphism in the promoter region of ELOVL6, ELOVL6:c.-533C>T, was highly associated with the percentage of palmitic and palmitoleic acids in muscle and backfat. Significant differences in ELOVL6 gene expression were observed in backfat when animals were classified by the ELOVL6:c.-533C>T genotype. Accordingly, animals carrying the allele associated with a decrease in ELOVL6 gene expression presented an increase in C16:0 and C16:1(n-7) fatty acid content and a decrease of elongation activity ratios in muscle and backfat. Furthermore, a SNP genome-wide association study with ELOVL6 relative expression levels in backfat showed the strongest effect on the SSC8 region in which the ELOVL6 gene is located. Finally, different potential genomic regions associated with ELOVL6 gene expression were also identified by GWAS in liver and muscle, suggesting a differential tissue regulation of the ELOVL6 gene.Conclusions and SignificanceOur results suggest ELOVL6 as a potential causal gene for the QTL analyzed and, subsequently, for controlling the overall balance of fatty acid composition in pigs.

Genome-wide analysis of porcine backfat and intramuscular fat fatty acid composition using high-density genotyping and expression data

“…The role of the ELOVL6 in fatty acid metabolism is even clearer, as it codes for a fatty acid elongase which catalyzes the elongation of FAs with 12–16 carbons to C18 [34]. Moreover, in a previous study conducted on the same animal material [17], the authors detected a strong effect of ELOVL6 :c.-533C > T SNP on C16:0 and C16:1 (n-7) percentages measured in BF and IMF. Furthermore, significant differences in ELOVL6 gene expression were observed when animals were classified by the ELOVL6 :c.-533C > T genotype in BF tissue, but not in Longissimus muscle.…”

“…Some studies with high-density chips using the Genome Wide Association approach (GWAS) have been carried out for detecting QTLs affecting FA content [11, 17]. Other studies based on classical models accounting for linkage allowed fine-mapping of significant QTLs not observed by GWAS [18].…”

Genetic association of DEGS1, ELOVL6, FABP3, FABP4, FASN and SCD genes with fatty acid composition in breast and thigh muscles of Korean native chicken

“…The DEGS1 , ELOVL6 , FASN and SCD genes result in the desaturation of fatty acids during the metabolism of fatty acids and the FABP3 and FABP4 genes in the lipid‐binding protein family regulate fatty acid uptake and transport. The genetic relationship studies of these genes with the fatty acid composition of meat have mainly examined beef and pork . In this study, we genotyped nine SNPs from the six candidate genes in a population of 597 F 1 birds generated from 88 F 0 parents from five Korean native chicken lines.…”

Genetic Marker Discovery in Complex Traits: A Field Example on Fat Content and Composition in Pigs

“…On the whole, GWAS regions explain in most cases a relatively small fraction (<8%) of the phenotypic variation. The possibility to dive into the genome has allowed the identification of solid candidate genes; for instance, for the SSC4 region affecting PUFA content in muscle ( APOA2 gene, [42]) or for the SSC8 region for palmitic and palmitoleic acid composition ( ELOVL6 , [43,44]). Although several mutations and epigenetic marks have been found in these genes, causality has not yet been proven.…”

“…For instance, several promoter mutations in the ELOVL fatty acid elongase 6 ( ELOVL6 ) gene have been associated with C16 (16:0 and 16:1) to C18 (18:0 and 18:1) content in longissimus dorsi muscle and backfat [43,44]. This enzyme elongates saturated and monounsaturated C12 to C18 fatty acids and it was a strong positional candidate gene for several compositional QTL at SSC8 in backfat [41,63] and muscle [40,64].…”