Myostatin Polymorphisms Research Articles

Polymorphisms and association analysis of the myostatin gene of the Chinese mitten crab (Eriocheir sinensis)

Marker-assisted selection (MAS) technology has been successfully applied in selective breeding of aquatic animals. Myostatin (MSTN) is a vital regulator of muscle growth, development, and differentiation. Five single-nucleotide polymorphisms (SNPs) of MSTN (S1: C712T; S2: C714T; S3: C716T; S4: A729G; S5: G753T) have potential application in MAS of Eriocheir sinensis (E. sinensis). Comparisons of the MSTN polymorphisms of wild, breeding and cultured populations of E. sinensis found that the S1 locus strongly deviated from the Hardy–Weinberg equilibrium in the breeding and cultured populations, likely due to continued selective breeding over the past 20 years. Associations of the five SNPs with the survival coefficient and body weight were assessed in cultured juvenile and adult crabs. The results found that the survival coefficient was significantly greater with the CC genotype at the S1 locus in male and female crabs (p < 0.05). Conversely, individuals with the TT genotype at the S1 locus had excellent growth characteristics, with significant differences only in male crabs (p < 0.05). These results suggested that the S1 locus of EsMSTN could be used for MAS of E. sinensis.

THE SINGLE NUCLEOTIDE POLYMORPHISMS OF MYOSTATIN GENE AND THEIR ASSOCIATIONS WITH GROWTH AND CARCASS TRAITS IN DAHENG BROILER

ABSTRACT Myostatin (MSTN) is a negative regulator of skeletal muscle growth. In order to investigate whether there is a correlation between MSTN polymorphisms and chicken production performance, in this study, single nucleotide polymorphisms (SNPs) in MSTN gene were examined across 180 Daheng broilers by direct sequencing of PCR product, and the correlations between the genotype and body weight at the age of 1-10 weeks and carcass traits at the age of 73 day were analyzed. Five SNPs (rs313622770, rs313744840, rs316247861, rs314431084, rs317126751) of MSTN gene were identified across Daheng broiler samples, and four haplotypes were reconstructed based on the five SNPs. Results of association analysis showed that four (rs313622770, rs313744840, rs316247861 and rs317126751) of these SNPs had significant association with some growth traits (p<0.05), but there were no significant effect on carcass traits and the four SNPs were strong linkage. For rs314431084, there was no significant correlation between different genotypes and growth or carcass traits. The AA genotype of rs313622770, GG genotype of rs313744840, CC genotype of rs316247861, TT genotype of rs317126751 were good for chicken growth. Diplotypes were significantly associated with chest muscle and leg muscle weight (p<0.05). Overall, these results provide evidence that polymorphisms in MSTN gene are associated with growth traits in chicken. The SNPs in MSTN gene could be utilized as potential markers for marker-assisted selection (MAS) during chicken breeding.

Enhanced estimates of carcass and meat quality effects for polymorphisms in myostatin and µ-calpain genes.

The objective of this study was to enhance estimates of additive, dominance, and epistatic effects of marker polymorphisms on beef carcass and quality traits. Myostatin (MSTN) F94L SNP and the µ-calpain (CAPN1) 316 and 4751 SNP haplotype have previously been associated with fat and muscle traits in beef cattle. Multiyear selection in a composite population segregating these polymorphisms increased minor allele (F94L L) and chosen haplotype (CAPN1 CC and GT) frequencies to intermediate levels resulting in more precise estimates of additive and nonadditive genetic effects. During the 3 yr after selection, 176 steers were evaluated for growth, carcass, meat quality, tenderness (n = 103), and meat color traits. The statistical model included year, age of dam, age of the steer, and genotype in a random animal model. The 9 genotypes (3 CAPN1 diplotypes × 3 F94L genotypes) affected marbling score, ribeye area, adjusted fat thickness, vision yield grade (all P < 0.001), slice shear force (P = 0.03), and CIE L* reflectance (P = 0.01). Linear contrasts of the 9 genotypes estimated additive, recessive, and epistatic genetic effects. Significant additive effects of the F94L L allele decreased marbling score, adjusted fat thickness, vision yield grade, and slice shear force; and increased ribeye area and CIE L* reflectance. The homozygous F94L FF and LL genotypes differed by 1.3 to 1.9 phenotypic SD for most carcass traits and by 0.8 to 0.9 SD for slice shear force and CIE L* reflectance but carcass weight differed by only 3 kg (0.1 SD). The L allele was partially recessive to F for ribeye area (P = 0.02) and the heterozygous FL means tended to be closer to the FF genotype than the LL genotype for other carcass traits but differences from additive were not significant. The CAPN1 additive × F94L additive effect on slice shear force was the only significant epistatic estimate. The F94L L allele is prevalent in Limousin but nearly absent in other U.S. purebreds. This allele had about half of the effects on birth weight, muscle, and fat traits reported for severe MSTN mutations in Belgian Blue and Piedmontese breeds. The interaction between MSTN and CAPN1 genotypes may reflect the strong additive effects of MSTN F94L L allele on fat and muscle traits interfering with the phenotypic effect of CAPN1 genotype on meat tenderness.

Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians.

Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the ‘highly oxidative/efficient’ rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a “healthy” metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved.

Frequencies of polymorphisms in myostatin vary in Icelandic horses according to the use of the horses.

Frequencies of polymorphisms in myostatin vary in Icelandic horses according to the use of the horses

Myostatin Gene Polymorphism in an Elderly Sarcopenic Turkish Population.

One of the genetic contributors to sarcopenia predisposition is Myostatin (MSTN), which in humans encodes myostatin, a 376 amino acid growth factor protein that negatively regulates muscle growth. The aim of this study was to investigate MSTN polymorphisms in an elderly sarcopenic population in Turkey and determine how they relate to sarcopenia. The study included nursing home residents who were aged ≥65 years. Sarcopenia screening was performed using "The European Working Group on Sarcopenia in Older People" guidelines. Blood sample was taken from each participant and DNA was obtained from the peripheral blood. MSTN polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism methods. A total of 152 elderly patients were included in the study. The rate of sarcopenia was determined to be 41.4%. The DNA nucleotide sequence of all three MSTN exons was determined for each study participant. Among the 152 patients, only 6 (3.9%) showed an MSTN K153R heterozygous mutation. Among these, three participants were sarcopenic and three were nonsarcopenic. No statistically significant difference in the polymorphism frequency between the sarcopenic and control groups was observed (p=0.664). MSTN genotyping revealed that only 3.9% (6/152) of participants had the MSTN K153R heterozygous mutation. Despite the detection of this mutation in the study group, no relationship was found between this mutation and sarcopenia.

Association of myostatin (MSTN) gene polymorphisms with morphological traits in the Italian Heavy Draft Horse breed

The myostatin (MSTN) gene encodes a protein well known as a negative regulator of muscle mass in mammalian species. In a previous study, we identified single nucleotide polymorphisms (SNPs) in the equine MSTN gene that could be associated with variability of morphological traits in different horse breeds. In this study we carried out a first evaluation of the association of MSTN gene with morphological traits and body measurements obtained at adult age in the Italian Heavy Draft Horse (IHDH), an autochthonous cold-blooded breed currently selected for meat production and for heavy draught. We genotyped 202 horses for four SNPs of the MSTN gene: two located in the promoter (GQ193900:g.26T>C and GQ193900:g.156T>C) and two in the first intron (GQ193900:g.2077T>C and GQ193900:g.2115A>G). Minor allele frequencies of SNPs varied from 0.118 to 0.148. The haplotype [g.26T:g.156T:g.2077T:g.2115A] showed the greater frequency (0.596). Biometric measurements of three body measurements (height at withers, chest girth, and cannon bone circumference) and 14 linear type data related to general aspects (head size and expression, temperament/blood, frame size, fleshiness and bone incidence), trunk (thorax depth, fore diameter, rear diameter, upper line length, and upper line direction) and feet and legs (e.g. side and back view of rear legs, fore and rear feet) were used in the association study. Among the investigated SNPs, the GQ193900:g.26T>C polymorphism was the most interesting as it resulted associated with cannon bone circumference (P nominal=0.001) and side view of rear legs (P nominal=0.006) and suggestively associated with fleshiness (P nominal=0.027). In silico transcription factors binding sites (TFBSs) prediction located putative TFBSs involved in growth and differentiation of multiple cell types, including myoblasts and osteoblasts in the SNP positions, suggesting that the analyzed SNPs could play a functional role. Gene expression studies should be carried out to verify this hypothesis. Further association studies in the present and other heavy horse breeds are needed to confirm the effects of MSTN polymorphisms on morphological traits, and potentially apply these markers in breeding programs to improve selection efficiency for muscularity and strength in horses.

Contribution of Myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring

Myostatin gene is a member of the transforming growth factor-β (TGF-β) family that negatively regulates skeletal muscle growth. Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women. The purpose of this study was to investigate whether myostatin played a role in the normal variation in peak BMD, lean mass (LM), and fat mass (FM) of Chinese men. Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited. Anthropometric measurements, including the peak BMD, body LM and FM were measured using dual-energy X-ray absorptiometry (DXA). The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing. Both rs2293284 and +2278GA were genotyped using TaqMan assay, and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis. The associations of the SNPs with anthropometric variations were analyzed using the quantitative transmission disequilibrium test (QTDT). Using QTDT to detect within-family associations, neither single SNP nor haplotype was found to be associated with peak BMD at any bone site. However, rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001). Moreover, for within-family associations, haplotypes AGG, AAA, and TGG were found to be significantly associated with the trunk fat mass (all P<0.001). Our results suggest that genetic variation within myostatin may play a role in regulating the variation in fat mass in Chinese males. Additionally, the myostatin gene may be a candidate that determines body fat mass in Chinese men.

Polymorphism of &lt;I&gt;MSTN&lt;/I&gt; gene and its association with growth traits in yellow catfish (&lt;I&gt;Pelteobagruse fulvidraco&lt;/I&gt;)

Myostatin (MSTN) gene has negative influence on the growth of muscle, which belongs to transforming growth factor-β family. Using single-strand conformation polymorphism (SSCP), single nucleotide polymorphisms (SNPs) of MSTN gene were detected in yellow catfish. Correlation analysis between MSTN polymorphisms and growth traits was also carried out. Results indicated that five genotypes (AA, BB, CC, CD and DD) were found in the first intron with one deletion site and two mutant sites (T1003del, G1022A and T1063G), two genotypes (EE and EF) were found in the third exon with one mutant site (T132C). The individuals with genotypes AA had a lager value than the individuals with the genotype CD and DD in total length, body length, body height, body width, head length and body weight (Plt;0.05). The female individuals with genotypes AA also had a lager value than the female individuals with genotypes DD in total length, body length, body height, body width, caudal peduncle height, caudal peduncle width and body weight (Plt;0.05). This implies that genotype AA has a positive influence on the growth traits of female yellow catfish, and genotype DD is opposite. Genotypes AA and DD can be used in marker assisted selection of female yellow catfish breeding in the future.

Single nucleotide polymorphisms in the myostatin (MSTN) and muscle creatine kinase (CKM) genes are not associated with elite endurance performance

Maximal oxygen uptake (VO2max) is one of the most important determinants of elite endurance performance. VO2max is determined by a whole range of genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in muscle myostatin (MSTN) and creatine kinase (CKM) genes are candidates for VO2max and skeletal muscle performance phenotypes. Common MSTN (rs3791783, rs11681628 and rs7570532) and CKM (rs344816, rs10410448, rs432979, rs1133190, rs7260359, rs7260463 and rs4884) SNPs, selected from HapMap CEU data in order to tag the genetic variability of the proteins, were genotyped in 316 male Caucasian elite endurance athletes and 304 sedentary controls from the Genathlete study. Association with elite endurance performance was determined by logistic regression analysis. The P-value for statistical significance was set at <0.01. None of the SNPs or haplotypes showed a significant association with elite endurance status. We conclude that common variants of MSTN and CKM genes do not play a role in attaining high-level endurance performance in Caucasian populations.

English

&nbsp; The objective of this study was to assess the association of polymorphisms in myostatin (MSTN) genes with growth and carcass traits in lines of Peking ducks. The polymorphism of the ducks MSTN gene promoter region was researched by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing methods. Three mutations: G-753A, G-658T and G-235C were detected in the duck MSTN gene. Altogether, 300 Peking ducks of three lines (Z2&nbsp;line, Z4&nbsp;line and Z2&times;Z4&nbsp;cross line) were genotyped and allele frequencies were determined. The effects of MSTN polymorphisms on growth and carcass traits were analyzed. The G-753A was significantly associated with breast meat percentages (BMP) (P = 0.0225). The G-235C indicated significant association with abdominal fat percentages (AFP) (P = 0.0297). No significant association, however, was detected between any of the marker genotype and other traits measured in this study. Results from this study suggest that MSTN gene-specific single-nucleotide polymorphism (SNP) may be a useful marker for growth and carcass traits in future marker assisted selection programs in ducks. &nbsp; Key words:&nbsp;Duck, myostatin gene, SNPs, PCR-SSCP, growth and carcass traits, association analysis.

Role of Myostatin Signaling in Aging: Applications for Age-Related Sarcopenia

Myostatin is a member of the TGFbeta family which is known to promote muscle wasting. Reduction of function mutations in this signaling molecule results in increased muscle mass in many different species examined including mice and humans. Age-related sarcopenia results in loss of strength and is a major contributing factor to falls and loss of independence in the elderly. Studies in rodents have demonstrated a decrease in myostatin expression in skeletal muscle whereas in humans there appears to be an increase in myostatin expression with age. Myostatin knockout mice have been reported to be resistant to the development of age-related sarcopenia and in humans, myostatin polymorphisms have been correlated with changes in muscle mass in the elderly. Treatment with an inhibitory antibody to myostatin increases muscle mass and, in combination with exercise, improves physical performance and metabolic parameters in aged mice and inhibition of myostatin pathway signaling with a dominant negative protein in aged mice speeds muscle regeneration after injury. Studies in old mice and rats suggest inhibition or loss of myostatin improves key features of skeletal muscle organization which are compromised in age-related sarcopenia and understanding the role of myostatin in aging skeletal muscle may reveal potential novel therapies for this unmet medical need. Keywords: Myostatin, aging, sarcopenia, TGFbeta, muscle, myofiber, motor neuron, TGF, GH, IGF-1, total body fat, Skeletal muscle, oxidative stress, mRNA, glycolytic fibers, hypertrophy, Genetic, Genomic, BrdU, WHASII, K153R, K153R allele, ACVR2B, PF-354, PCNA, immunoreactive, Testosterone, myoanabolic, FDA, mmobilization

Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families

We identified 17 polymorphisms in myostatin by sequencing, and three informative single nucleotide polymorphisms (SNPs) were selected for further observation for their association with peak BMD of women in 401 Chinese nuclear families. Our results suggest that genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women. Myostatin is a TGF-beta family member that is a negative regulator of skeletal muscle growth. We identified SNPs in myostatin by direct sequencing. Furthermore, using a quantitative transmission disequilibrium test (QTDT). we tested and further test whether SNPs were associated with peak bone mineral density (BMD) variation at the spines and hips of 401 Chinese nuclear families. We identified 17 polymorphisms in myostatin by sequencing. Next, we selected three informative SNPs for further observation of an association with peak BMD of premenopausal women in 401 Chinese nuclear families. Using QTDT for the within-family association, we found significant association between rs2293284 and total hip, femoral neck, and trochanter BMD (all p < 0.05), while rs7570532 was associated with total hip and trochanter BMD (p = 0.034 and p = 0.035, respectively). The within-family association was significant between BMI and +2278G > A (p = 0.022). Subsequent permutations were in agreement with these significant within-family association results. Moreover, analyses of the haplotypes confer further evidence for association of rs2293284 and rs7570532 with hip peak BMD variation. These results suggest, for the first time, the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women.

Associations of myostatin gene polymorphisms with performance and mortality traits in broiler chickens

Myostatin is a negative regulator of skeletal muscle growth. We evaluated effects of myostatin polymorphisms in three elite commercial broiler chicken lines on mortality, growth, feed conversion efficiency, ultrasound breast depth, breast percentage, eviscerated carcass weight, leg defects, blood oxygen level, and hen antibody titer to infectious bursal disease virus vaccine. Progeny mean data adjusted for fixed and mate effects and DNA from 100 sires per line were used. Single nucleotide polymorphisms (SNPs) of the myostatin gene segregating in these lines were identified by designing specific primers, amplifying individual DNA in each line by polymerase chain reaction, cloning, sequencing and aligning the corresponding products. Individual sires were genotyped for five identified SNPs which contributed to eight haplotypes. Frequencies of SNP alleles and haplotypes differed between lines. Using the allele substitution effect model, the myostatin SNPs were found to have significant (P < 0.031) associations with growth, mortality, blood oxygen and hen antibody titer to infectious bursal disease virus vaccine, although the associations were not often consistent across lines. These results suggest that the myostatin gene has pleiotropic effects on broiler performance.

Associations of myostatin gene polymorphisms with performance and mortality traits in broiler chickens

Myostatin is a negative regulator of skeletal muscle growth. We evaluated effects of myostatin polymorphisms in three elite commercial broiler chicken lines on mortality, growth, feed conversion efficiency, ultrasound breast depth, breast percentage, eviscerated carcass weight, leg defects, blood oxygen level, and hen antibody titer to infectious bursal disease virus vaccine. Progeny mean data adjusted for fixed and mate effects and DNA from 100 sires per line were used. Single nucleotide polymorphisms (SNPs) of the myostatin gene segregating in these lines were identified by designing specific primers, amplifying individual DNA in each line by polymerase chain reaction, cloning, sequencing and aligning the corresponding products. Individual sires were genotyped for five identified SNPs which contributed to eight haplotypes. Frequencies of SNP alleles and haplotypes differed between lines. Using the allele substitution effect model, the myostatin SNPs were found to have significant (P < 0.031) associations with growth, mortality, blood oxygen and hen antibody titer to infectious bursal disease virus vaccine, although the associations were not often consistent across lines. These results suggest that the myostatin gene has pleiotropic effects on broiler performance.

Individual Variations in Exercise Training-induced Physiological Effects and Genetic Factors

Regular exercise training brings about desirable physical effects, including an increase in both endurance capacity and muscle strength/volume and an improvement in arterial stiffness that regulate blood pressure. However, these effects vary greatly between individuals. In addition to environmental factors, the genetic backgrounds causing those individual variations are inferred. Research exploring genes which regulate physical capabilities and training-induced effects is widely being implemented. These studies will encourage an individually tailored prescription of lifestyle/exercise for health. This review focused on individual variations of exercise training-induced effects on physical endurance capacity, muscle strength/volume and arterial stiffness. The relation between these effects and the gene and genetic factors, and future perspectives were discussed. Concerning endurance capacity, many studies have been carried out on ACE genotype, and also the relation to polymorphisms of mtDNA, UCP gene or HIF1A gene. In our studies, the polymorphisms of mitochondria-related genes were explored, revealing a suggestion that polymorphism is related to the endurance capacity and the phenotypes in skeletal muscles. Regarding muscle strength and volume, polymorphisms in myostatin, AMPD and CNTFR have been investigated. Our study observed genes that indicated expression dynamics related to exercise training effects on muscle strength and volume. As a result of investigation of genes concerned with arterial stiffness improvements by exercise training, changes in many gene expressions were found. Moreover, using the genes regulated by the training as candidates, training-induced effects on arterial stiffness and polymorphisms of these candidate genes were studied. The results suggest the possibility of genetic factors influencing training-induced effects on arterial stiffness. Genetic factors are clearly involved in exercise training-induced effects on endurance capacity, muscle strength/volume and arterial stiffness. Considering the effects of exercise training, the time is approaching when genetic factors will be taken into consideration.

Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes

This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin (GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 (P = 0.0002). Second, maximum LOD scores of 3.4 (P = 0.00004) and 3.3 (P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12-14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22-23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.