The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle

We herein report new evidence that the QTL effect on chromosome 20 in Finnish Ayrshire can be explained by variation in two distinct genes, growth hormone receptor (GHR) and prolactin receptor (PRLR). In a previous study in Holstein-Friesian dairy cattle an F279Y polymorphism in the transmembrane domain of GHR was found to be associated with an effect on milk yield and composition. The result of our multimarker regression analysis suggests that in Finnish Ayrshire two QTL segregate on the chromosomal region including GHR and PRLR. By sequencing the coding sequences of GHR and PRLR and the sequence of three GHR promoters from the pooled samples of individuals of known QTL genotype, we identified two substitutions that were associated with milk production traits: the previously reported F-to-Y substitution in the transmembrane domain of GHR and an S-to-N substitution in the signal peptide of PRLR. The results provide strong evidence that the effect of PRLR S18N polymorphism is distinct from the GHR F279Y effect. In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested.     

Polymorphism within the 3' flanking region of the bovine growth hormone receptor gene

Growth hormone receptor (GHR) has a major role in the regulation of growth hormone action, and thus, is an obvious candidate gene associated with milk production traits in mammals. The present authors have sequenced 273 bp of the 3' flanking region of the bovine GHR , and found three length variants and one base substitution polymorphism in this region. Allele frequencies of the length variants differ between Finnish native and commercial dairy cattle breeds. The chromosomal localization of GHR was confirmed to bovine chromosome 20 by synteny mapping and linkage analysis.     

Study of the association between alleles of the growth hormone receptor and prolactin receptor genes of bulls and the milk productivity of their daughters

A substitution of thyrosine for phenylalanine (F297Y) in the transmembrane domain of the growth hormone receptor (GHR) was tested for significance for breeding evaluation of bulls of the holstenized Black-and-White breed. The breeding value was estimated by the method of daughter yield deviation to contemporaries with modification. The frequency of genotype FF in the bulls examined was 0.37, lower than in Holstein bulls (0.67). The F297Y substitution exerted the greatest effect on the milk fat content (1.5??) and milk yield (0.8 ??) and a lower effect on the milk fat yield (0.6 ??), milk protein yield (0.5 ??), and milk protein content (0.6 ??). The GHR4.2 single nucleotide substitution (SNP) in the promoter of the GHR gene did not affect the milk production traits. A substitution of asparagine for serine (S18N) in the transmembrane domain of the prolactin receptor (PRLR) was also examined, but it did not significantly affect the milk production traits. The results are discussed in the context of the hypothesis that multiplicity of causal mutations of a particular gene is common and should be taken into account in the genetics of quantitative traits.     

Associations of the IGF2 gene with growth and meat efficiency in Large White pigs

The insulin-like growth factor 2 gene (IGF2) has been described in several studies as a candidate gene for meat efficiency in pigs. IGF2 is a member of the growth factors family and has an effect on development of muscle tissue. The effect of IGF2 gene polymorphism on meat efficiency was analysed in a population of 121 Large White pigs. A PCR-based test and RFLP methods were used for detection of genotypes. Allele A, lacking the restriction site, was characterised by the presence of a 0.9-kb fragment. In allele B, the amplimer was cut into a 0.8-kb fragment and some barely detectable fragments. The statistical analysis was carried out according to the General Linear Model procedure. The genotype frequencies observed were: 1.65%, 33.88%, 64.46% for AA, AB and BB genotypes, respectively. There was a significant difference (P < or = 0.05) between the AB and BB genotypes in live weight before the test. A significant association between AB and BB genotypes and body weight before the test was found. No significant difference in other traits of growth and meat efficiency was observed (P > 0.05).     

Synergistic and threshold effects of GH1 and GHR promoter size variation on body growth and fat accrual in young Nelore (Bos indicus) bulls

A synergistic effect in the somatotropic axis (GH1-GHR-IGF1) was observed in 736 young Nelore (Bos indicus) bulls under ad libitum grass feeding conditions on irrigated pasture in central Brazil. Stepwise substitution of shorter alleles of the promoter region of the growth hormone gene (GH1) and the P1 promoter of the GH1 receptor gene (GHR) with longer alleles was associated with significantly increased body weight gain (W550, weight at age 550 days; ADG, average daily gain) and fat accrual (FAT, rib eye fat thickness). A threshold effect on ADG was associated with allele size variation at the GH1. A best fit model indicated a 3- to 6-fold effect of GH1 variation on ADG, when compared to the variation at the GHR and a known microsatellite at the somatomedin gene (IGF1, insulin-like growth factor 1). A threshold effect on FAT was associated with substitution of the short GHR allele by the longer GHR alleles; the effect of the GHR variation on FAT was 10-fold that of the variation at the GH1 and IGF1 loci. Among the 10 GH1-GHR-IGF1 multi-genotypes identified, the predominant genotype was homozygous for the large GH1 promoter (long/long, G2/G2 or domestic type), short GHR promoter (short/short or wild type), and short IGF1 microsatellite (short/short or wild type). This predominant multi-genotype suggests that selection pressure in the Nelore breed has been directed towards high ADG and W550, and low FAT. Our results mirror previous findings in the oMtla-oGH transgenic mouse model, in which the level of somatotropic gene expression acts through a threshold mechanism, and low expression results in adipogenesis, while high expression increases body growth.     

Association and haplotype analysis of purH gene with inosine monophosphate content in chickens

The current study was designed to investigate the effects of the purH gene on chicken muscle inosine monophosphate (IMP) content. Muscle IMP content was measured in five chicken breeds. Single nucleotide polymorphisms (SNPs) were detected by PCR-SSCP and DNA sequencing. Two SNPs were detected, A/T substitution at position 8023 in exon 9, and T/C substitution at position 17446 in exon 16. The results indicated that only T17446C polymorphism was associated with IMP content. The haplotype effect was higher than the single genotype effect. We tentatively conclude that purH gene is a candidate locus or linked to a major gene that affects muscle IMP content. Haplotypes are superior to single genotypes as potential molecular markers for meat quality traits in chicken.     

Effect of myostatin F94L on carcass yield in cattle

In this study, a highly significant quantitative trait locus (QTL) for meat percentage, eye muscle area (EMA) and silverside percentage was found on cattle chromosome 2 at 0-15 cM, a region containing the positional candidate gene growth differentiation factor 8 (GDF8), which has the common alias myostatin (MSTN). Loss-of-function mutations in the MSTN gene are known to cause an extreme 'double muscling' phenotype in cattle. In this study, highly significant associations of MSTN with cattle carcass traits were found using maternally inherited MSTN haplotypes from outbred Limousin and Jersey cattle in a linkage disequilibrium analysis. A previously reported transversion in MSTN (AF320998.1:g.433C>A), resulting in the amino acid substitution of phenylalanine by leucine at position 94 of the protein sequence (F94L), was the only polymorphism consistently related to increased muscling. Overall, the size of the g.433C>A additive effect on carcass traits was moderately large, with the g.433A allele found to be associated with a 5.5% increase in silverside percentage and EMA and a 2.3% increase in total meat percentage relative to the g.433C allele. The phenotypic effects of the g.433A allele were partially recessive. This study provides strong evidence that a MSTN genotype can produce an intermediate, non-double muscling phenotype, which should be of significant value for beef cattle producers.     

AGHR polymorphism and its associations with carcass traits in Harrwoo cattle

The growth hormone receptor (GHR) is a membrane transmitter for the growth hormone signal transduction pathway that regulates various metabolic activities, including cell growth and expressions of cytokine genes. The presence or absence of a genetic polymorphism for the LINE-1 retroposon in the PI promoter, which specifically regulates theGHR gene expression in the liver, was screened by a novel detection method and examined for its relationships with carcass traits in Hanwoo cattle. Han woo cattle had taurine type LINE-1 present (alleleI) as well as incidine type LINE-1 absent (alleleA) promoter sequences. Three genotypes,I/I, I/A andA/A, showed frequencies of 49.1, 36.7 and 14.2%, respectively. The effects of allele A were significant on mean differences for final weight, eye muscle area, marbling score and fat color (p<0.05), but not for carcass weight, backfat thickness, final meat quality grade or meat color (p>0.05). Most 30-month old Hanwoo steers bearing the LINE-1 absent promoter had whiter fat color, heavier live weight and higher marbling score, reflecting intramuscular fat deposition inM. longissimus dorsi, compared to animals bearing a LINE-1 present promoter. This suggests that aGHR polymorphism could be a potential genetic marker for improving beef production of Hanwoo cattle.     

北极狐GHR基因单核苷酸多态性及其与生长性状的相关性分析

文章采用单链构象多态性(PCR-SSCP)和DNA测序的方法检测了北极狐生长激素受体(Growth hormne receptor, GHR)基因的单核苷酸多态性(SNPs), 并针对该群体的特点建立合适的统计分析模型, 对GHR基因多态性与生长性状的相关性进行了分析。结果表明, 在北极狐GHR基因的外显子1和外显子5上发现了4个多态位点, 分别为5′UTR上的G3A和外显子1上的C99T突变, 外显子5上的T59C和G65A突变; GHR基因G3A和C99T多态性与母狐的体重性状显著相关(P<0.05), T59C和G65A多态性与公狐的体重性状显著相关(P<0.05), 与母狐的皮张长度性状极显著相关(P<0.01)。因此, 可以利用以上点突变对北极狐的体重及皮张长度性状进行标记辅助选择研究, 以达到快速选育出快大、优质的北极狐的目的。     

Association and Haplotype Analysis of purH Gene with Inosine Monophosphate Content in Chickens

The current study was designed to investigate the effects of the purH gene on chicken muscle inosine monophosphate (IMP) content. Muscle IMP content was measured in five chicken breeds. Single nucleotide polymorphisms (SNPs) were detected by PCR-SSCP and DNA sequencing. Two SNPs were detected, A/T substitution at position 8023 in exon 9, and T/C substitution at position 17446 in exon 16. The results indicated that only T17446C polymorphism was associated with IMP content. The haplotype effect was higher than the single genotype effect. We tentatively conclude that purH gene is a candidate locus or linked to a major gene that affects muscle IMP content. Haplotypes are superior to single genotypes as potential molecular markers for meat quality traits in chicken.     

Biochemical, ECF18R, and RYR1 Gene Polymorphisms and Their Associations with Osteochondral Diseases and Production Traits in Pigs

This study reports the association of five blood types, three enzymes, two proteins, Escherichia coli F18 receptor gene (ECF18R), and the Ryanodin receptor (RYR1) gene with six production traits, four meat quality traits, and two osteochondral diseases in Swiss pig populations. Data on on-farm traits (daily weight gain, percent premium cuts, and backfat) and on station-tested traits (daily weight gain, feed conversion ratio, meat quality, and osteochondral lesions) were available on 3,918 and 303 animals, respectively. A mixed linear model with allele substitution effects was used for each trait by marker analysis (144 analyses). Significant marker-trait associations and allele substitution effects are presented. In general, heritability estimates for production and meat quality traits were higher than those for osteochondral lesions. Blood types lack significant associations with many traits except H and S types. Enzymes (mainly, glucose phosphate isomerase) and protein polymorphisms show significant associations with daily weight gain, premium cuts, and backfat as well as osteochondral lesions. The RYR and ECF18R genes significantly affected all growth, production, and lean meat content traits and osteochondral lesions; RYR also affected pH values. This study reports many novel marker-trait associations, particularly between the incidence of osteochondral lesions and polymorphisms at glucose phosphate isomerase, 6-phosphogluconate dehydrogenase, postalbumin 1A, RYR, and ECF18R loci. These results should be useful in selection and for further functional genomics and proteomics investigations.     

Effects of DGAT1 and GHR on milk yield and milk composition in the Chinese dairy population

Previous studies have demonstrated that the p.Lys232Ala substitution in the acylCoA: diacylglycerol acyltransferase ( DGAT1 ) gene and the p.Phe279Tyr mutation in the growth hormone receptor ( GHR ) gene are the causative quantitative trait loci underlying milk yield and composition on BTA14 and BTA20 respectively. To examine their applications in the genetic improvement of Chinese dairy cattle productivity, we herein investigated the effects of the DGAT1 p.Lys232Ala and GHR p.Phe279Tyr mutations on milk, fat and protein yield, as well as fat and protein percentage in the milk of 1222 Holstein cows. Genotyping was performed using PCR-RFLP for DGAT1 or primer-introduced restriction analysis (PCR-PIRA) for GHR . With a mixed animal model, the significant associations of the DGAT1 p.Lys232Ala substitution with 305-day milk, fat and protein yield were identified ( P  =   0.0001). The DGAT1 allele that encode lysine at position 232 was associated with increased 305-day milk fat yield, but with decreased 305-day milk and protein yield, whereas the GHR p.Phe279Tyr mutation was found to be significantly associated with protein percentage ( P  =   0.0014). The allele substitution effect of p.279Phe by p.279Tyr may lead to a significant increase in protein percentage. Our findings indicate that DGAT1 p.232Ala and GHR p.279Phe could be used to increase milk yield and protein yield of Chinese Holstein cows.     

Associations between newly discovered polymorphisms in the Bos taurusgrowth hormone receptor gene and performance traits in Holstein–Friesian dairy cattle

Variations in the growth hormone receptor (GHR) gene sequence are associated with performance traits in cattle. For example, the single nucleotide polymorphism (SNP) F279Y in transmembrane exon 8 has a strong association with milk yield. In this study, 32 previously unreported, putative novel SNPs (31 in the 5′ non‐coding region) were identified by resequencing ～19 kb of the GHR gene in genomic DNA from 22 cattle of multiple breeds. A population of 848 Holstein–Friesian AI sires was subsequently genotyped for the 32 putative novel SNPs and seven published SNPs (including F279Y, one in exon 1A promoter and five in exon 10). Associations between each segregating SNP and genetic merit for performance were quantified in the 848 Holstein–Friesians using weighted animal linear mixed models. Six of the published SNPs and seven of the novel SNPs were associated with at least one of the traits – milk yield, fat yield, protein yield, fat percentage, protein percentage, somatic cell score, calving interval, survival and growth and size traits. Even when the allelic substitution effect (P < 0.001) of F279Y was accounted for, the allelic substitution effect of one of the novel SNPs (GHR4.2) in the 5′ non‐coding region of GHR was associated with a lactation milk yield of 37.46 kg (P < 0.001). GHR4.2 and F279Y were not in linkage disequilibrium (r² = 0.00, D’ = 0.04) in the 848 Holstein–Friesians, indicating that their association with milk yield was independent.     

Genetic variants affecting meat and milk production traits appear to have effects on reproduction traits in cattle

Polymorphisms located in the genes ABCG2, DGAT1, LEP, PRLR, RORC, CAPN1 and CAST previously have been associated with milk or meat production traits. In this study, these polymorphisms were examined for significant effects on reproductive traits [age at puberty (AGECL), post-partum anoestrus interval (PPAI) and the ability ovulate prior to weaning (PW)] and on a panel of correlated traits such as weight, growth and serum concentration of insulin-like growth factor I. The effects of the polymorphisms were examined in two samples of tropically adapted beef cattle: Brahman (N = 932) and Tropical Composites (N = 1097). A polymorphism in the gene DGAT1 was associated with age at puberty in the combined sample (P = 0.042), and two polymorphisms in CAPN1 were associated with PPAI (P = 0.033) and with the ability ovulate PW (P = 0.017). The favourable allele for reproductive traits was not always the favourable allele associated with production traits. The effects of these polymorphisms on reproductive traits were small compared to their effects on the traits for which they were originally discovered.     

Single nucleotide polymorphisms in CAPN and leptin genes associated with meat color and tenderness in Nellore cattle

We analyzed single nucleotide polymorphisms in calpain, leptin, leptin receptor, and growth hormone receptor genes and their association with color, drip and cooking losses of longissimus muscle at 7, 14 and 21 days postmortem in 638 purebred Nellore bulls slaughtered between 22 and 26 months of age. Meat samples were vacuum-packed and aged at 4°C. The single nucleotide polymorphisms T945M, GHR2, E2FB, and CAPN4751 were evaluated. All genotypic classes were observed; however, the T/T genotype of T945M and E2FB was found at a low frequency. A significant association of E2FB with drip loss (a measure of water-holding capacity) was detected at seven days of meat aging. CAPN4751 had an additive effect on red and yellow color intensities. The T allele of CAPN4751 was found to be positively associated with improved meat color, but not with meat tenderness, differing from a previous report indicating that it is associated with meat tenderness. We conclude that the potential for use of CAPN4751 as a marker for these meat quality traits requires further research.     

Association of corticotropin-releasing hormone gene variation with performance and meat quality traits in commercial pig lines

The porcine corticotropin-releasing hormone(CRH) gene is a functional-positional candidate for quantitative tract loci on porcine chromosome 4 with major effects on growth and carcass composition. In addition, the central role of CRH in the neuroendocrine response to stress implicates the CRH gene as a functional candidate for meat quality. Association of a single nucleotide polymorphism (SNP) in the promoter region of the porcine CRH gene (g.233C > T) with several growth, carcass and meat quality traits was examined using more than 2000 individuals from four commercial lines: German Landrace (LR), Pietrain (Pi), German Large White x German Landrace (F1) and the German commercial fattening pig cross of Pietrain x F1 (PiF1). Significant association of the CRH SNP was found with feed conversion ratio in the PiF1 line, with carcass length in the LR line and with lean content in the F1, LR and Pi lines. Moreover, significant association with meat colour was found in the Pi and LR lines; however, the effects were in opposite directions. The presented results indicate that sequence variation in the porcine CRH gene has no major effect on growth and carcass composition in commercial pig lines, although it may significantly contribute to variation in meat quality. The g.233C>T SNP may be in incomplete linkage disequilibrium with causal mutations and/or exhibit effects in the context of DNA variation at other interacting loci.     

Association of melanocortin 4 receptor (MC4R) and high mobility group AT-hook 1 (HMGA1) polymorphisms with pig growth and fat deposition traits

The aim of this study was to analyse the combined effect of melanocortin 4 receptor (MC4R) and high mobility group AT-hook 1 (HMGA1) polymorphisms on growth and fatness traits in Duroc pigs. No significant interaction was observed between MC4R and HMGA1 for back-fat traits. An additive mode of inheritance of both gene effects was found for average daily gain and lean meat content. Maximum mean differences from combined genotypic effects were over 2 mm for back fat, 70 g/day for average daily gain and 2% for lean meat content. Therefore, utilization of polymorphisms in both MC4R and HMGA1 for marker-assisted selection could result in an economic benefit to the pig industry.     

Impact of the ESR gene on litter size and production traits in Czech Large White pigs

To evaluate the effect of the PvuII polymorphism of the oestrogen receptor gene on litter size and production traits in Czech Large White swine, data from 1250 sows and 3600 litters were analysed with two four-trait animal models. The traits in the first model were number of piglets born alive in a sow's first litter, number of piglets born alive in second and subsequent litters, lifetime daily gain and lean meat percentage. The second model included number of piglets born, number of piglets born alive, number of piglets weaned and litter weight at weaning from first and subsequent litters. The oestrogen receptor (ESR) locus significantly affected prolicacy in the first parity and averaged over all parities (P < 0.05), with allele A superior to allele B. In the first parity, AA sows produced approximately 0.5 more live piglets per litter than BB sows. Averaged over all parities, this difference was c. 0.25 piglets. Results for total number of piglets born and number of piglets weaned were similar to results for numbers born alive. No significant dominance effect was found for prolificacy traits. For litter weight at weaning, no significant additive effect was observed at the ESR locus, but a significant negative dominance effect (-1.5 kg) was estimated averaged across parities (litters of AB sows were similar to litters of BB sows for this trait). No pleiotropic effect of the ESR polymorphism on average daily gain or lean meat percentage was found.     

苏姜猪OLR1基因多态性及其与肉质性状的关联分析

探讨OLR1基因在苏姜猪群内的遗传多态性,以及该基因多态对苏姜猪猪肉质性状的影响。采用PCR-RFLP技术检测OLR1基因在苏姜猪试验群体中的PstⅠ酶切遗传多态性,运用单因素方差分析方法分析了该多态位点对苏姜猪肉质性状的影响。结果发现,苏姜猪试验群体OLR1基因内含子5区域内发现一个PstⅠ酶切多态性,检测到CC、CD和DD三种基因型,多态信息含量呈现中度多态性。CC型与DD型个体的肌肉失水率、大理石纹间的差异达到显著水平(P<0.05),CD型个体用色差仪测得的b值显著高于DD型(P<0.05)。因此,检测到的OLR1基因PCR-RFLP-PstⅠ多态性与大理石纹等肉质性状存在着显著的相关关系,可以作为肉质性状候选基因在苏姜猪的持续选育中加以应用。