Analysis of non-synonymous SNPs of the porcineSERPINA6gene as potential causal variants for a QTL affecting plasma cortisol levels on SSC7

Abstract

Recently, the SERPINA6 gene encoding corticosteroid-binding globulin (CBG) has been proposed as a candidate gene for a quantitative trait locus (QTL) affecting cortisol level on pig chromosome 7. The QTL was repeatedly detected in different lines, including a Piétrain × (German Landrace × German Large White) cross (PiF1) and purebred German Landrace (LR). In this study, we investigated whether the known non-synonymous polymorphisms c.44G>T, c.622C>T, c.770C>T, c.793G>A, c.832G>A and c.919G>A of SERPINA6 are sufficient to explain the QTL in these two populations. Our investigations revealed that SNPs c.44G>T, c.622C>T, c.793G>A and c.919G>A are associated with cortisol level in PiF1 (P < 0.01). Haplotype analysis showed that these associations are largely attributable to differences between a major haplotype carrying SNPs c.793G>A and c.919G>A and a haplotype carrying SNPs c.44G>T and c.622C>T. Furthermore, some SNPs, particularly c.44G>T and c.622C>T and the carrier haplotype, showed association with meat quality traits including pH and conductivity (P < 0.05). In LR, the non-synonymous SNPs segregate at very low frequency (<5%) and/or show only weak association with cortisol level (SNPs c.832G>A and c.919G>A; P < 0.05). These findings suggest that the non-synonymous SNPs are not sufficient to explain the QTL across different breeds. Therefore, we examined whether the expression of SERPINA6 is affected by cis-regulatory polymorphisms in liver, the major organ for CBG production. We found allelic expression imbalance of SERPINA6, which suggests that its expression is indeed affected by genetic variation in cis-acting elements. This represents candidate causal variation for future studies of the molecular background of the QTL.

Genome-Wide Detection of Allele Frequency Change and Quantitative Trait Loci for Respiratory Disease and Immune-Related Traits in Landrace Pigs Selected for Mycoplasmal Pneumonia of Swine Resistance

“…The significant additive QTL for CORT_105 was detected on SSC7, and the corticosteroid-binding globulin (CBG, also known as SERPINA6) gene was regarded as a positional candidate gene in the QTL region. The SERPINA6 gene encodes CBG affecting cortisol-binding capacity and SNPs at the SERPINA6 locus influence plasma cortisol levels in humans [42] and pigs [39,40,41]. Our results supported the finding that the SERPINA6 gene would be a positional candidate gene for CORT_105.…”

“…GWAS detected a total of six significant additive QTL and three significant nonadditive QTL, as well as a positional candidate gene by genome-wide QTL mapping, which was previously only reported in the SSC7 region of CORT_105 specimens in different breeds [39,40,41]. The significant additive QTL for CORT_105 was detected on SSC7, and the corticosteroid-binding globulin (CBG, also known as SERPINA6) gene was regarded as a positional candidate gene in the QTL region.…”

Investigation of allele-specific expression of genes involved in adipogenesis and lipid metabolism suggests complex regulatory mechanisms of PPARGC1A expression in porcine fat tissues

“…Allelic expression imbalance has also been analyzed for several genes thought to affect pig meat quality and fatness traits. Deviations between allelic transcript levels were detected for ADRB2 in l. dorsi muscle [ 24 ], SERPINA6 and APOA2 in liver [ 25 , 26 ] but not for ADIPOQ in skeletal muscles and backfat [ 27 ]. Our study analyzed ASE of four functional candidate genes encoding transcription factors ( PPARA, PPARG, SREBF1 ) and a coactivator of multiple transcription factors ( PPARGC1A ) using pyrosequencing as an accurate and sensitive means of quantifying allelic transcript proportions [ 28 ].…”

Omics Application in Animal Science—A Special Emphasis on Stress Response and Damaging Behaviour in Pigs

“…They found that the substitution Gly307Arg, originating from domestic pigs [ 115 ], increases CBG capacity and decreases CBG affinity for cortisol. However, the amino acid substitutions do not fully explain the QTL in any of the populations where the QTL has been detected [ 114 , 116 , 117 ]. Apart from coding variation, SERPINA6 function is apparently diversified by regulatory variation [ 114 , 117 ].…”

“…However, the amino acid substitutions do not fully explain the QTL in any of the populations where the QTL has been detected [ 114 , 116 , 117 ]. Apart from coding variation, SERPINA6 function is apparently diversified by regulatory variation [ 114 , 117 ]. Thus, the causal effect might result from an interaction of the regulatory with the coding variation.…”