Association of functional sequence variants of the myosin heavy chain 3 gene with muscle collagen content in pigs.

This study examined the association between functional sequence variants (FSVs) of myosin heavy chain 3 (MYH3) genotypes and collagen content in a Landrace and Jeju native pig (JNP) crossbred population. Four muscles (Musculus longissimus dorsi, Musculus semimembranosus, Musculus triceps brachii, and Musculus biceps femoris) were used for the analysis of meat collagen content, and the same animals were genotyped for the FSVs of the MYH3 gene by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Three FSVs of MYH3 genotypes were identified and had genotype frequencies of 0.358, 0.551, and 0.091 for QQ, Qq, and qq, respectively. QQ animals for the FSVs of the MYH3 genotypes showed higher collagen content in their M. longissimus dorsi (p < 0.001), M. semimembranosus (p < 0.001), M. triceps brachii (p < 0.001), and M. biceps femoris (p < 0.001) than qq homozygous animals. After the validation of this result in other independent populations, the FSVs of MYH3 genotypes can be a valuable genetic marker for improving collagen content in porcine muscles and can also be applied to increase the amount of collagen for biomedical purposes.

GWAS and Post-GWAS High-Resolution Mapping Analyses Identify Strong Novel Candidate Genes Influencing the Fatty Acid Composition of the Longissimus dorsi Muscle in Pigs.

Fatty acid (FA) composition is one of the most important parameters for the assessment of meat quality in pigs. The FA composition in pork can also affect human health. Our aim was to identify quantitative trait loci (QTLs) and positional candidate genes affecting the FA profile of the longissimus dorsi muscle in a large F2 intercross between Landrace and Korean native pigs comprising 1105 F2 progeny by genome-wide association studies (GWAS) and post-GWAS high-resolution mapping analyses. We performed GWAS using the PorcineSNP60K BeadChip and a linear mixed model. Four genome-wide significant QTL regions in SSC8, SSC12, SSC14, and SSC16 were detected (p < 2.53 × 10-7). Several co-localizations of QTLs in SSC12 for oleic acid, linoleic acid, arachidonic acid, monounsaturated FAs, polyunsaturated FAs, and the polyunsaturated/saturated FA ratio were observed. To refine the QTL region in SSC12, a linkage and linkage disequilibrium analysis was applied and could narrow down the critical region to a 0.749 Mb region. Of the genes in this region, GAS7, MYH2, and MYH3 were identified as strong novel candidate genes based on further conditional association analyses. These findings provide a novel insight into the genetic basis of FA composition in pork and could contribute to the improvement of pork quality.

A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs.

Muscle development and lipid accumulation in muscle critically affect meat quality of livestock. However, the genetic factors underlying myofiber-type specification and intramuscular fat (IMF) accumulation remain to be elucidated. Using two independent intercrosses between Western commercial breeds and Korean native pigs (KNPs) and a joint linkage-linkage disequilibrium analysis, we identified a 488.1-kb region on porcine chromosome 12 that affects both reddish meat color (a*) and IMF. In this critical region, only the MYH3 gene, encoding myosin heavy chain 3, was found to be preferentially overexpressed in the skeletal muscle of KNPs. Subsequently, MYH3-transgenic mice demonstrated that this gene controls both myofiber-type specification and adipogenesis in skeletal muscle. We discovered a structural variant in the promotor/regulatory region of MYH3 for which Q allele carriers exhibited significantly higher values of a* and IMF than q allele carriers. Furthermore, chromatin immunoprecipitation and cotransfection assays showed that the structural variant in the 5'-flanking region of MYH3 abrogated the binding of the myogenic regulatory factors (MYF5, MYOD, MYOG, and MRF4). The allele distribution of MYH3 among pig populations worldwide indicated that the MYH3 Q allele is of Asian origin and likely predates domestication. In conclusion, we identified a functional regulatory sequence variant in porcine MYH3 that provides novel insights into the genetic basis of the regulation of myofiber type ratios and associated changes in IMF in pigs. The MYH3 variant can play an important role in improving pork quality in current breeding programs.

Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats.

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague- Dawley rats.