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. 2013;8(1):e53687.
doi: 10.1371/journal.pone.0053687. Epub 2013 Jan 14.

Polymorphism in the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs

Jordi Corominas  1 , Yuliaxis Ramayo-Caldas, Anna Puig-Oliveras, Dafne Pérez-Montarelo, Jose L Noguera, Josep M Folch, Maria Ballester
Affiliations

Polymorphism in the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs

Jordi Corominas et al. PLoS One. 2013.

Abstract

Background: The 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 findings: The 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 significance: Our 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Reduction of the QTL interval by GWAS and LDLA analyses and gene mapping of ELOVL6.
Plot of GWAS (blue points) and LDLA patterns (red line) for palmitic (A) and palmitoleic (B) acids. The X-axis represents chromosome 8 positions in Mb and the Y-axis shows the –log10 (p-value). The vertical green line represents the position of the ELOVL6 gene on SSC8. Horizontal dashed lines mark the genome-wide significance level (FDR-based q-value≤0.05). Positions in Mb are relative to Sscrofa10.2 assembly of the pig genome.
Figure 2
Figure 2. Genetic characterization of the ELOVL6 pig promoter and identification of potential cis-acting DNA-sequence motifs.
Summary of the ELOVL6 pig promoter: A, nucleotide sequence of the 5′-flanking region of the porcine ELOVL6 gene, where potential binding sites for transcription factors are underlined. Positions of ELOVL6 promoter polymorphisms are labeled in yellow. B, comparison of transcription factor binding sites between mouse and the pig ELOVL6 promoter, including ELOVL6 SNPs localization.
Figure 3
Figure 3. Association of ELOVL6: c.-533C>T genotypes on gene expression in backfat.
A SNP genome-wide association study was performed with ELOVL6 relative expression levels measured by RT-qPCR in 110 samples from backfat, liver and muscle. Data include: Schematic representation of the elongation pathway of 16-carbon fatty acid (A), ELOVL6 expression levels in backfat (B), liver (C) and muscle (D). Data represent means ± SEM. Values with different superscript letters (a, b and c) indicate significant differences between groups (p-value < 0.05), as determined by a single stratum analysis of variance considering sex and batch as fixed effects.
Figure 4
Figure 4. Fatty acid composition of different ELOVL6:c.-533C>T genotypes in muscle and backfat.
Data include: percentage of C16:0 (A) and C16:1(n-7) fatty acids (B) in muscle and backfat; and the elongation ratios C18:0/C16:0 (C) and C18:1(n-7)+C18:1(n-9)/C16:0 (D) in muscle and backfat. Data represent mean ± SEM. Values with different superscript letters (a, b and c) indicate significant differences between groups (p-value < 0.05), as determined by a single stratum analysis of variance considering sex and batch as fixed effects.
Figure 5
Figure 5. Significant region obtained in GWAS for backfat gene expression.
Association analysis between the backfat ELOVL6 expression level and SNP genotypes for SSC2 (A), SSC4 (B) and SSC8 (C). ELOVL6 polymorphisms are included and labeled with a red circle. Positions in Mb are relative to Sscrofa10.2 assembly of the pig genome. Vertical, dashed lines indicate the location of positional candidate genes. Horizontal, dashed lines mark the genome-wide significance level (FDR-based q-value≤0.1).
Figure 6
Figure 6. Significant region obtained in GWAS for liver gene expression.
Association analysis between the liver ELOVL6 expression level and SNP genotypes for SSC4. Positions in Mb are relative to Sscrofa10.2 assembly of the pig genome. Vertical, dashed lines indicate the location of positional candidate genes. Horizontal, dashed lines mark the chromosome-wide significance level (FDR-based q-value≤0.1).
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Grants and funding

This study has been funded by MICINN projects (AGL2008-04818-C03 and AGL2011-29821-CO2) and the Innovation Consolider-Ingenio 2012 Program (CSD2007-00036, Center for Research in Agrigenomics). J. Corominas was funded by a Formación de Personal Investigador (FPI) PhD grant from Spanish Ministerio de Educación (BES-2009-018223), Y. Ramayo by a Formación del Profesorado Universitario (FPU) PhD grant (AP2008-01450) and A. Puig was funded by a Personal Investigador en Formación (PIF) PhD grant from the Universitat Autónoma de Barcelona (458-01-1/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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