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1.
Genet Sel Evol ; 51(1): 29, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221081

RESUMO

BACKGROUND: Selection of cattle that are less sensitive to environmental variation in unfavorable environments and more adapted to harsh conditions is of primary importance for tropical beef cattle production systems. Understanding the genetic background of sensitivity to environmental variation is necessary for developing strategies and tools to increase efficiency and sustainability of beef production. We evaluated the degree of sensitivity of beef cattle performance to environmental variation, at the animal and molecular marker levels (412 K single nucleotide polymorphisms), by fitting and comparing the results of different reaction norm models (RNM), using a comprehensive dataset of Nellore cattle raised under diverse environmental conditions. RESULTS: Heteroscedastic RNM (with different residual variances for environmental level) provided better fit than homoscedastic RNM. In addition, spline and quadratic RNM outperformed linear RNM, which suggests the existence of a nonlinear genetic component affecting the performance of Nellore cattle. This nonlinearity indicates that within-animal sensitivity depends on the environmental gradient (EG) level and that animals may present different patterns of sensitivity according to the range of environmental variations. The spline RNM showed that sensitivity to environmental variation from harsh to average EG is lowly correlated with sensitivity from average to good EG, at both the animal and molecular marker levels. Although the genomic regions that affect sensitivity in harsher environments were not the same as those associated with less challenging environments, the candidate genes within those regions participate in common biological processes such as those related to inflammatory and immune response. Some plausible candidate genes were identified. CONCLUSIONS: Sensitivity of tropical beef cattle to environmental variation is not continuous along the environmental gradient, which implies that animals that are less sensitive to harsher conditions are not necessarily less responsive to variations in better environmental conditions, and vice versa. The same pattern was observed at the molecular marker level, i.e. genomic regions and, consequently, candidate genes associated with sensitivity to harsh conditions were not the same as those associated with sensitivity to less challenging conditions.


Assuntos
Bovinos/genética , Interação Gene-Ambiente , Animais , Feminino , Estudo de Associação Genômica Ampla/veterinária , Masculino , Polimorfismo de Nucleotídeo Único , Clima Tropical , Ganho de Peso/genética
2.
J Anim Sci ; 97(6): 2450-2459, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31100117

RESUMO

One hundred ninety-one Angus steers (age = 546 d ± 33.5; BW = 36.4 kg ± 4.2), sired by bulls divergently selected for feed efficiency over a 3-yr period, were used to compare growth, efficiency, body composition, and carcass characteristics. Selected Angus sires were either high (Hi) or low (Lo) for residual average daily gain (RADG) expected progeny differences (EPDs) and either high (Hi) or low (AVG; breed average) for marbling (MARB) EPDs. Steer weight and body composition, via ultrasound, were measured at weaning (205 d) and at 1 yr (365 d) of age. Steers entered the feedlot at 454 d of age and completed a 70-d GROWSAFE BEEF System evaluation to determine DMI, ADG, and residual feed intake (RFI). Steers were then slaughtered as they reached a backfat thickness of 1.3 cm. Carcasses were chilled for 48 h at 2 °C, ribbed, and USDA yield and quality grade data were collected. The right side of the carcass was fabricated and primal and subprimal weights were collected. A 2.5-cm longissimus steak was removed, vacuum-packaged, aged for 14 d, and frozen for slice shear force determination. Additionally, a 1.3-cm longissimus steak was removed from year 3 steers for proximate analysis. The GLM procedure of SAS was used and the main effects of RADG and MARB and their interaction were tested by the error term, SIRE(RADG*MARB). Year was evaluated as a replicate. Weight, ultrasound backfat, and REA were increased (P ≤ 0.05) at weaning in the Hi compared with AVG MARB steers. Feed efficiency, measured by RFI, was improved (P = 0.05) in the Hi RADG steers compared with Lo RADG steers. Slaughter weight and HCW were heavier (P ≤ 0.03) in the Hi RADG steers compared with Lo RADG steers. An interaction (P = 0.05) between RADG and MARB selection was found for marbling score, steers selected for Lo RADG and Hi MARB had greater marbling scores than all other groups. Longissimus proximate composition from year 3 showed that lipid content was greater (P < 0.01) in the Hi MARB and Lo RADG groups compared with the AVG MARB and Hi RADG groups, respectively. These findings suggest that selection using RADG or MARB EPDs has minimal impact on carcass yield. However, positive selection pressure placed on these breeding values can potentially improve efficiency and carcass quality. Lastly, it appears that improvements in feed efficiency can be obtained without negatively affecting beef carcass merit, especially USDA quality grade.


Assuntos
Composição Corporal/genética , Cruzamento , Carne/normas , Ganho de Peso/genética , Animais , Composição Corporal/fisiologia , Bovinos/genética , Masculino , Seleção Genética
3.
Genet Sel Evol ; 51(1): 13, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991944

RESUMO

BACKGROUND: We used stable isotope profiling (15N and 13C) to obtain indicator phenotypes for feed efficiency in aquaculture. Our objectives were to (1) examine whether atom percent of stable isotopes of nitrogen and carbon can explain more of the variation in feed conversion ratio than growth alone, and (2) estimate the heritabilities of and genetic correlations between feed efficiency, growth and indicator traits as functions of nitrogen and carbon metabolism in various tissues. A 12-day experiment was conducted with 2281 Atlantic salmon parr, with an average initial weight of 21.8 g, from 23 full-sib families that were allocated to 46 family tanks and fed an experimental diet enriched with 15N and 13C. RESULTS: Using leave-one-out cross-validation, as much as 79% of the between-tank variation in feed conversion ratio was explained by growth, indicator traits, and sampling day, compared to 62% that was explained by growth and sampling day alone. The ratio of tissue metabolism, estimated by a change in isotope fractions relative to body growth, was used as an individual indicator for feed efficiency. For these indicator ratio traits, the estimated genetic correlation to feed conversion ratio approached unity but their heritabilities were low (0.06 to 0.11). These results indicate that feed-efficient fish are characterized by allocating a high fraction of their metabolism to growth. Among the isotope indicator traits, carbon metabolism in the liver had the closest estimated genetic correlation with feed conversion ratio on a tank level (- 0.9) but a low estimated genetic correlation with individually recorded feed efficiency indicator ratio traits. The underlying determinants of these correlations are largely unknown. CONCLUSIONS: Our findings show that the use of indicator ratio traits to assess individual feed efficiency in Atlantic salmon has great prospects in selection programs. Given that large quantities of feeds with contrasting isotope profiles of carbon and/or nitrogen can be produced cost-effectively, the use of stable isotopes to monitor nitrogen and carbon metabolism in various tissues has potential for large-scale recording of individual feed efficiency traits, without requiring individual feed intake to be recorded.


Assuntos
Aquicultura/métodos , Salmo salar/genética , Seleção Genética/genética , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cruzamento/métodos , Isótopos de Carbono/metabolismo , Dieta , Genótipo , Nitrogênio/metabolismo , Isótopos de Nitrogênio/metabolismo , Fenótipo , Característica Quantitativa Herdável , Salmo salar/fisiologia , Ganho de Peso/genética
4.
BMC Womens Health ; 19(1): 33, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30755194

RESUMO

BACKGROUND: Although family factors can greatly impact adult health, little is known about the extent to which family factors are related to body weight gain (BWG) in adulthood. This study aimed to examine the associations between family factors and BWG from 20 years old. METHODS: Among the 6395 possible participants aged 35 to 79 years, 2884 men and 2171 women were eligible for the study. Present body mass indexes (BMI) were measured, and family factors and body weight from 20 years old (i.e., BMI_20yr) were collected using a self-administered questionnaire. The differences between BMI and BMI_20yr were calculated, and those with increases of BMI ≥2.5 kg/m2 (i.e., ≥7.5 and 6.0 kg in men and women, respectively) were defined as 'cases' of BWG. Using a multiple logistic regression analysis, the odds ratios (ORs, 95% confidence intervals [CIs] and p for trend) were estimated. RESULTS: In the men, no association was found. In the women, the ORs were 0.31, 1.00 and 0.77 (0.17-0.58, [reference], and (0.52-1.29), p < 0.001) as per their marital status: unmarried, married, and bereaved/divorced, respectively. Although no association was found with family structure (i.e., single, couple, and two and three generations living together), for familial relationships, the ORs were 1.00, 1.11 and 1.86 ([reference], 0.85-1.46, and 1.25-2.79, p < 0.01) for 'good', 'somewhat good', and 'not so good/not good', respectively. Even if a 'case' of BWG was ≥3.5 kg/m2, nearly the same risks remained. CONCLUSION: Marital status and family relationships were associated with decreased and increased risks of BWG only in the female participants. Family factors should be considered when advising women on body weight control.


Assuntos
Índice de Massa Corporal , Peso Corporal/genética , Peso Corporal/fisiologia , Características da Família , Ganho de Peso/genética , Ganho de Peso/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco , Adulto Jovem
5.
PLoS Genet ; 15(2): e1007970, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30768595

RESUMO

Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-κB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes.


Assuntos
Inflamação/prevenção & controle , Doenças Metabólicas/prevenção & controle , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Expressão Gênica , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/prevenção & controle , Inflamação/genética , Inflamação/metabolismo , Insulina/sangue , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Macrófagos/metabolismo , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/antagonistas & inibidores , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/prevenção & controle , Proteínas Proto-Oncogênicas c-akt/genética , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/genética
6.
J Anim Breed Genet ; 136(3): 168-173, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30687950

RESUMO

The aim of this experiment was to evaluate the significance of neonatal environment on feed efficiency. For that purpose, rabbits from a line selected for residual feed intake (RFI) during 10 generations (G10 kits) were cross-fostered with non-selected control does (i.e., G0 line), and reciprocally. In parallel, sibs were fostered by mothers from their original line. Nine hundred animals were raised in individual (N = 456) or collective (N = 320) cages. Traits analysed in this study were body weight at 32 days and at 63 days, average daily gain (ADG), feed intake between weaning and 63 days (FI), feed conversion ratio (FCR) and RFI. The maternal environment offered by does from the line selected for RFI deteriorated the FCR of the kits, independently of their line of origin, during fattening (+0.08 ± 0.02) compared to FCR of kits nursed by G0 does. The line, the type of housing and the batch were significant effects for all the measured traits: G10 kits were lighter than their G0 counterparts at 32 days (-82.9 ± 9 g, p < 0.0001) and at 63 days (-161 ± 16 g, p < 0.0001). They also had a lower ADG (-2.36 ± 0.36 g/day, p < 0.0001), RFI (-521 ± 24 g/day, p < 0.0001) and a lower FI (-855 ± 31 g, p < 0.0001), resulting in a more desirable feed efficiency (FCR: -0.35 ± 0.02). There was no significant difference in the contrast of G10 and G0 performances between collective and individual/digestive cages (p > 0.22): -2.35 g/day versus 2.94 g/day for ADG, -0.39 versus -0.40 for FCR, -577 g versus -565 g for RFI and -879 g versus -859 g for FI, respectively). Thus, no genotype-by-environment (housing) interaction is expected at the commercial level, that is, no re-ranking of the animals due to collective housing.


Assuntos
Peso Corporal/genética , Cruzamento , Herança Materna/genética , Ganho de Peso/genética , Ração Animal , Animais , Ingestão de Alimentos/genética , Genótipo , Carne , Fenótipo , Coelhos
7.
BMC Genomics ; 20(1): 31, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630414

RESUMO

BACKGROUND: Average daily gain (ADG) is an important trait that contributes to the production efficiency and economic benefits in the beef cattle industry. The molecular mechanisms of ADG have not yet been fully explored because most recent association studies for ADG are based on SNPs or haplotypes. We reported a systematic CNV discovery and association analysis for ADG in Chinese Simmental beef cattle. RESULTS: Our study identified 4912 nonredundant CNVRs with a total length of ~ 248.7 Mb, corresponding to ~ 8.9% of the cattle genome. Using probe-based CNV association, we identified 24 and 12 significant SNP probes within five deletions and two duplications for ADG, respectively. Among them, we found one common deletion with 89 kb imbedded in LHFPL Tetraspan Subfamily Member 6 (LHFPL6) at 22.9 Mb on BTA12, which has high frequency (12.9%) dispersing across population. CNV selection test using VST statistic suggested this common deletion may be under positive selection in Chinese Simmental cattle. Moreover, this deletion was not overlapped with any candidate SNP for ADG compared with previous SNPs-based association studies, suggesting its important role for ADG. In addition, we identified one rare deletion near gene Growth Factor Receptor-bound Protein 10 (GRB10) at 5.1 Mb on BTA4 for ADG using both probe-based association and region-based approaches. CONCLUSIONS: Our results provided some valuable insights to elucidate the genetic basis of ADG in beef cattle, and these findings offer an alternative perspective to understand the genetic mechanism of complex traits in terms of copy number variations in farm animals.


Assuntos
Bovinos/genética , Variações do Número de Cópias de DNA , Deleção de Sequência , Ganho de Peso/genética , Animais , Sequência de Bases , Proteína Adaptadora GRB10/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Carne Vermelha
8.
Neurosci Bull ; 35(3): 561-580, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30607769

RESUMO

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.


Assuntos
Antipsicóticos/efeitos adversos , Testes Farmacogenômicos , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Metabolismo dos Lipídeos/genética , Sistemas Neurossecretores/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos/genética , Receptores Dopaminérgicos/genética , Receptores Histamínicos/genética , Receptores de Serotonina/genética
9.
Transplant Proc ; 51(1): 164-166, 2019 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30655132

RESUMO

The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation. METHODS: In 198 kidney transplant recipients, FTO rs9939609 was investigated in association with body mass index (BMI)/obesity and with other clinical markers of posttransplant risk, then monitored up to 5 years after transplantation. Genotyping was performed using an allelic discrimination method on a real-time polymerase chain (PCR) system. Associations were analyzed using the chi-square test; differences between genotypes were examined with analysis of variance or Kruskal-Wallis test; tests for repeated measures and a general linear model analysis controlling for age and gender were also utilized. RESULTS: Allele and genotype frequencies of FTO rs9939609 in recipients (T/T, 29.8%; T/A, 49.0%; A/A, 21.2%; A, 45.7%; T, 54.3%) reflect those present in healthy Caucasian populations. In the face of pre-/posttransplant differences in total cholesterol, triglycerides, or fasting glucose, results did not show significant changes in these factors among genotypes either before or after transplantation. CONCLUSION: This study highlights a lack of association of FTO rs9939609T>A genotypes and posttransplant weight gain, plasma lipids, and fasting blood glucose in kidney transplantation.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Transplante de Rim , Obesidade/genética , Ganho de Peso/genética , Adulto , Glicemia/genética , Índice de Massa Corporal , Colesterol/sangue , Colesterol/genética , Feminino , Genótipo , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Triglicerídeos/sangue , Triglicerídeos/genética
10.
Eur Neuropsychopharmacol ; 29(2): 211-221, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30554862

RESUMO

Weight gain is a common adverse effect of lithium augmentation. Previous studies indicate an impact of genetic variants at the leptin gene on weight gain as a consequence of psychopharmacological treatment. The primary aim of our study was to identify variants at the leptin locus that might predict lithium-induced weight gain. The secondary aim was to investigate if these variants modulate leptin levels. In 180 patients with acute major depressive disorder, body mass index was measured before and after 4 weeks of lithium augmentation, in a subsample also after 4 and/or 7 months. In a subsample of 89 patients, leptin serum concentrations were measured before and during lithium augmentation. We used linear mixed model analyzes to investigate the effects of 2 polymorphisms at the leptin locus (rs4731426 and rs7799039, employing the respective proxy SNPs rs2278815 and rs10487506) on changes in body mass index and leptin levels. For both polymorphisms, which are in high linkage disequilibrium, body mass index was significantly lower in homozygous A-allele carriers than in carriers of other genotypes at baseline. Over the follow-up period, body mass index increased less in homozygous A-allele carriers of rs4731426 than in carriers of other genotypes. This was not the case for rs7799039. Neither polymorphism modulated leptin protein expression. Our study strongly supports the hypothesis that genetic variability at the leptin locus is involved in lithium augmentation-associated weight gain in major depressive disorder. Furthermore, Genotype-Tissue Expression data provide strong evidence that rs4731426 influences the expression of leptin messenger ribonucleic acid in fibroblasts.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Leptina/genética , Lítio/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/genética , Adulto , Transtorno Depressivo Maior/sangue , Feminino , Genótipo , Humanos , Peso Corporal Ideal , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos
11.
Anim Sci J ; 89(10): 1381-1388, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30073716

RESUMO

Genetic parameters and trends in the average daily gain (ADG), backfat thickness (BF), loin muscle area (LMA), lean percentage (LP), and age at 90 kg (D90) were estimated for populations of Landrace and Yorkshire pigs. Additionally, the correlations between these production traits and litter traits were estimated. Litter traits included total born (TB) and number born alive (NBA). The data used for this study were obtained from eight farms during 1999 to 2016. Analyses were carried out with a multivariate animal model to estimate genetic parameters for production traits while bivariate analyses were performed to estimate the correlations between production and litter traits. The heritability estimates were 0.52 and 0.43 for ADG; 0.54 and 0.45 for BF; 0.25 and 0.26 for LMA; 0.54 and 0.48 for LP; and 0.56 and 0.46 for D90 in the Landrace and Yorkshire breeds, respectively. The ADG and D90 showed low genetic correlation with BF and LP. The LMA had -0.40, -0.32, 0.49, and 0.39 genetic correlations with ADG, BF, LP, and D90, respectively. Genetic correlations between production and litter traits were generally low, except for the correlations between LMA and TB (-0.23) in Landrace and ADG and TB (-0.16), ADG and NBA (-0.18), D90 and TB (0.19), and D90 and NBA (0.20) in Yorkshire. Genetic trends in production traits were all favorable except for LMA.


Assuntos
Estudos de Associação Genética/veterinária , Tamanho da Ninhada de Vivíparos/genética , Característica Quantitativa Herdável , Reprodução/genética , Suínos/anatomia & histologia , Suínos/genética , Suínos/fisiologia , Tecido Adiposo/anatomia & histologia , Animais , Feminino , Masculino , Músculo Esquelético/anatomia & histologia , Ganho de Peso/genética
12.
Psychopharmacology (Berl) ; 235(9): 2665-2673, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29984389

RESUMO

RATIONALE: Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect. OBJECTIVE: The aim of this study was to investigate the association of selected single nucleotide polymorphisms (SNPs) of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor γ (PPARγ) with VPA-induced weight gain and obesity in epileptic patients. METHODS: A total of 225 Chinese Han epilepsy patients receiving VPA treatment were recruited in the study. Height and weight for the calculation of body mass index (BMI) were measured at the initiation of VPA therapy and in the follow-up examination. A BMI of 25 kg/m2 or higher was defined as obesity on the basis of the World Health Organization (WHO) criteria for Asian populations. Four SNPs in CD36 (rs1194197, rs7807607) and PPARγ (rs10865710, rs2920502) were genotyped using the Sequenom® MassArray iPlex platform. RESULTS: About 19.6% of epileptic patients receiving VPA therapy were found to become obese. After covariate analysis of age, gender, sex, height, initial BMI, and VPA dosage, the CD36 rs1194197 C allele and rs7807607 T allele (OR, 0.31; 95%CI, 0.13-0.72; P = 0.009 and OR, 0.38; 95%CI; 0.18-0.83; P = 0.02, respectively) were identified as protective factors for VPA-induced obesity. The PPARγ rs10865710 C allele carriers were found to be less likely to suffer from VPA-induced obesity compared with GG genotype carriers (OR, 0.04; 95%CI, 0.01-0.12; P < 0.001). After a Bonferroni correction for multiple comparisons, the genotypic associations of CD36 rs1194197 and PPARγ rs10865710 and the allelic association of CD36 rs7807607 with obesity remained statistically significant. CONCLUSIONS: Our data first indicated that CD36 and PPARγ polymorphisms may be associated with VPA-induced obesity and weight gain, suggesting that CD36 and PPARγ may have potential value in predicting VPA-induced obesity in Chinese Han epileptic patients.


Assuntos
Anticonvulsivantes/efeitos adversos , Antígenos CD36/genética , Epilepsia/genética , Obesidade/genética , PPAR gama/genética , Ácido Valproico/efeitos adversos , Adolescente , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Peso Corporal/genética , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Obesidade/induzido quimicamente , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/genética , Adulto Jovem
13.
Genet Sel Evol ; 50(1): 33, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925306

RESUMO

BACKGROUND: This study aimed at (1) deriving Bayesian methods to predict breeding values for ratio (i.e. feed conversion ratio; FCR) or linear (i.e. residual feed intake; RFI) traits; (2) estimating genetic parameters for average daily feed consumption (ADFI), average daily weight gain (ADG), lean meat percentage (LMP) along with the derived traits of RFI and FCR; and (3) deriving Bayesian estimates of direct and correlated responses to selection on RFI, FCR, ADG, ADFI, and LMP. Response to selection was defined as the difference in additive genetic mean of the selected top individuals, expected to be parents of the next generation, and the total population after integrating genetic trends out of the posterior distribution of selection responses. Inferences were based on marginal posterior distributions obtained from the Bayesian method for integration over unknown population parameters and "fixed" environmental effects and for appropriate handling of ratio traits. Terminal line pigs (n = 3724) were used for a multi-variate model for ADFI, ADG, and LMP. RFI was estimated from the conditional distribution of ADFI given ADG and LMP, using either genetic (RFIG) or phenotypic (RFIP) partial regression coefficients. The posterior distribution of the FCR's breeding values was derived from the posterior distribution of "fixed" environmental effects and additive genetic effects on ADFI and ADG. RESULTS: Posterior means of heritability were 0.32, 0.26, 0.56, 0.20, and 0.15 for ADFI, ADG, LMP, RFIP, and RFIG, respectively. Selection against RFIG showed a direct response of - 0.16 kg/d and correlated responses of - 0.16 kg/kg for FCR and - 0.15 kg/d for ADFI, with no effect on other production traits. Selection against FCR resulted in a direct response of - 0.17 kg/kg and correlated responses of - 0.14 kg/d for RFIG, - 0.18 kg/d for ADFI, and 0.98% for LMP. CONCLUSIONS: The Bayesian methodology developed here enables prediction of breeding values for FCR and RFI from a single multi-variate model. In addition, we derived posterior distributions of direct and correlated responses to selection. Genetic parameter estimates indicated a genetic basis for the studied traits and that genetic improvement through selection was possible. Direct selection against FCR or RFIP resulted in unexpected responses in production traits.


Assuntos
Cruzamento , Expressão Gênica , Característica Quantitativa Herdável , Seleção Genética , Animais , Teorema de Bayes , Feminino , Masculino , Carne/análise , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Suínos , Ganho de Peso/genética
14.
Acta Diabetol ; 55(9): 901-908, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29855804

RESUMO

AIMS: Previous genome-wide association studies reported rs1440581 was significantly associated with circulating branched chain amino acids (BCAAs) levels in Europeans. We aimed to investigate association of BCAAs related variant rs1440581 with incident T2D risk and longitudinal changes in glucose-related metabolic traits in a community-based prospective cohort of Chinese. METHODS: 6043 non-diabetic participants aged ≥ 40 years from a community-based population at baseline were included and followed-up for 5 years. The BCAAs related variant rs1440581 was genotyped. Incident T2D was defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L or taking anti-diabetic therapy. Anthropometry and biochemical measurements were evaluated at both baseline and follow-up. RESULTS: 576 (9.5%) participants developed T2D during the 5-year follow-up. Each C-allele was associated with a 20% higher risk of incident T2D (odds ratio = 1.20, 95% confidence interval [1.05, 1.36]) after adjustments for the confounders. We did not find a main effect of the variant on increase in fasting serum insulin (FSI) level or insulin resistance (IR). However, we found rs1440581 significantly modified effect of weight gain on increase in FSI and HOMA-IR. In the C-allele carriers, body mass index increase was associated with greater increase in Log10_FSI (ß ± SE 0.027 ± 0.002) and Log10_HOMA-IR (0.030 ± 0.003), as compared to T-allele (both P for interaction = 0.003). CONCLUSIONS: BCAAs related genetic variant rs1440581 was associated with an increased risk of incident T2D in a Chinese population. This variant might modify effect of weight gain on development in IR.


Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único , Proteína Fosfatase 2C/genética , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ganho de Peso/genética
15.
J Anim Sci ; 96(7): 2579-2595, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29741705

RESUMO

The objective of the present study was to evaluate the accuracy and bias of direct and blended genomic predictions using different methods and cross-validation techniques for growth traits (weight and weight gains) and visual scores (conformation, precocity, muscling, and size) obtained at weaning and at yearling in Hereford and Braford breeds. Phenotypic data contained 126,290 animals belonging to the Delta G Connection genetic improvement program, and a set of 3,545 animals genotyped with the 50K chip and 131 sires with the 777K. After quality control, 41,045 markers remained for all animals. An animal model was used to estimate (co)variance components and to predict breeding values, which were later used to calculate the deregressed estimated breeding values (DEBV). Animals with genotype and phenotype for the traits studied were divided into 4 or 5 groups by random and k-means clustering cross-validation strategies. The values of accuracy of the direct genomic values (DGV) were moderate to high magnitude for at weaning and at yearling traits, ranging from 0.19 to 0.45 for the k-means and 0.23 to 0.78 for random clustering among all traits. The greatest gain in relation to the pedigree BLUP (PBLUP) was 9.5% with the BayesB method with both the k-means and the random clustering. Blended genomic value accuracies ranged from 0.19 to 0.56 for k-means and from 0.21 to 0.82 for random clustering. The analyses using the historical pedigree and phenotypes contributed additional information to calculate the GEBV, and in general, the largest gains were for the single-step (ssGBLUP) method in bivariate analyses with a mean increase of 43.00% among all traits measured at weaning and of 46.27% for those evaluated at yearling. The accuracy values for the marker effects estimation methods were lower for k-means clustering, indicating that the training set relationship to the selection candidates is a major factor affecting accuracy of genomic predictions. The gains in accuracy obtained with genomic blending methods, mainly ssGBLUP in bivariate analyses, indicate that genomic predictions should be used as a tool to improve genetic gains in relation to the traditional PBLUP selection.


Assuntos
Bovinos/genética , Genoma/genética , Genômica , Polimorfismo de Nucleotídeo Único/genética , Animais , Peso Corporal/genética , Cruzamento , Bovinos/crescimento & desenvolvimento , Análise por Conglomerados , Feminino , Genótipo , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Linhagem , Fenótipo , Desmame , Ganho de Peso/genética
16.
J Anim Sci ; 96(7): 2536-2544, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29741708

RESUMO

The objective of this study was to compare growth from birth to slaughter of different breed groups that were raised in Rio Grande do Sul, Brazil and estimate the consequent breed additive and heterosis effects. Caracu (C), Hereford (H), and Nelore (N) sires were mated with Angus (A) dams, and A sires were mated with H and N dams to produce a first generation of crossbred progeny that was contemporary with purebred A, H, and N calves. Heifers from this first generation (G1) were mated with Brangus (BN) and Braford (BO) sires to produce a second generation (G2) of progeny. Data were analyzed to estimate breed group means, individual and maternal breed additive effects, and heterosis effects on birth weight, weaning weight, preweaning average daily gain, yearling weight, postweaning average daily gain, fattening phase initial weight (around 19 mo), final weight (around 24 mo), average daily gain in the fattening phase, and age at slaughter. In general, crossbred calves outperformed purebred calves. Angus-N and CA crossbred cows weaned heavier calves. Individual taurine-indicine heterosis (Z) significantly increased weaning weight. The AN, NA, and CA steers were heaviest at yearling, whereas NA, CA, AN, and HA had the greatest final weights. However, AH steers were 1 mo older at slaughter than NA contemporaries. Taurine breed effects on postweaning traits and final weight were greater than for N. Maternal breed effects on birth weight and average daily gain in the fattening phase were greater for A and H than for N. In conclusion, heterosis effects were sufficiently large for use of N to be recommended as a component of such systems, despite their relatively low-breed additive effects compared with taurine breeds. Moreover, germplasm from the tropically adapted Bos taurus C may be particularly useful when increased milk production is desired. With the breed and heterosis effects derived in the present study, it is possible to predict the performance and infer which breed and breed crosses will perform better in crossbreeding systems designed for the subtropical conditions of southern Brazil and similar regions.


Assuntos
Peso ao Nascer/genética , Bovinos/crescimento & desenvolvimento , Vigor Híbrido , Reprodução , Animais , Brasil , Bovinos/genética , Bovinos/fisiologia , Cruzamentos Genéticos , Feminino , Hibridização Genética , Masculino , Parto , Fenótipo , Gravidez , Desmame , Ganho de Peso/genética
17.
Genet Sel Evol ; 50(1): 25, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29747574

RESUMO

BACKGROUND: Indirect genetic effects (IGE) are important components of various traits in several species. Although the intensity of social interactions between partners likely vary over time, very few genetic studies have investigated how IGE vary over time for traits under selection in livestock species. To overcome this issue, our aim was: (1) to analyze longitudinal records of average daily gain (ADG) in rabbits subjected to a 5-week period of feed restriction using a structured antedependence (SAD) model that includes IGE and (2) to evaluate, by simulation, the response to selection when IGE are present and genetic evaluation is based on a SAD model that includes IGE or not. RESULTS: The direct genetic variance for ADG (g/d) increased from week 1 to 3 [from 8.03 to 13.47 (g/d)2] and then decreased [6.20 (g/d)2 at week 5], while the indirect genetic variance decreased from week 1 to 4 [from 0.43 to 0.22 (g/d)2]. The correlation between the direct genetic effects of different weeks was moderate to high (ranging from 0.46 to 0.86) and tended to decrease with time interval between measurements. The same trend was observed for IGE for weeks 2 to 5 (correlations ranging from 0.62 to 0.91). Estimates of the correlation between IGE of week 1 and IGE of the other weeks did not follow the same pattern and correlations were lower. Estimates of correlations between direct and indirect effects were negative at all times. After seven generations of simulated selection, the increase in ADG from selection on EBV from a SAD model that included IGE was higher (~ 30%) than when those effects were omitted. CONCLUSIONS: Indirect genetic effects are larger just after mixing animals at weaning than later in the fattening period, probably because of the establishment of social hierarchy that is generally observed at that time. Accounting for IGE in the selection criterion maximizes genetic progress.


Assuntos
Ração Animal , Restrição Calórica/veterinária , Ganho de Peso/genética , Animais , Cruzamento , Simulação por Computador , Feminino , Gado , Estudos Longitudinais , Masculino , Coelhos
19.
PLoS One ; 13(5): e0196983, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29795582

RESUMO

Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer's disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome ("metaflammasome") mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome. In wild type (WT) and PKR-/- mice, blood glucose, insulin and lipid levels and the brain expression of the phosphorylated components of the metaflammasome-PKR, JNK, IRS1 and IKKbeta-were studied after the induction of obesity by a high fat diet (HFD). The results showed significant increased levels of activated brain metaflammasome proteins in exposed WT mice but the changes were not significant in PKR-/- mice. In addition, gain weight was observed in WT mice and also in PKR-/- mice exposed to HFD. Increased blood insulin level was more accentuated in PKR -/- mice. The modulation of PKR activity could be an appropriate therapeutic approach, aimed at reducing abnormal brain metabolism and inflammation linked to metabolic disorders in order to reduce the risk of neurodegeneration.


Assuntos
Glicemia/metabolismo , Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Insulina/sangue , Obesidade/metabolismo , eIF-2 Quinase/genética , Animais , Encéfalo/patologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamação , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/genética , Obesidade/patologia , Transdução de Sinais , Triglicerídeos/sangue , Ganho de Peso/genética , eIF-2 Quinase/deficiência
20.
Obesity (Silver Spring) ; 26(3): 492-498, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29399976

RESUMO

OBJECTIVE: During weight loss, the volume of adipocytes decreases, leading to stress because of the misfit between the cell contents and the surrounding extracellular matrix (ECM). This stress can be resolved by remodeling the ECM or the restorage of triglycerides within the adipocytes. The objective of this study was to investigate the existence of a connection between stress-related and ECM-related genes that is associated with weight regain. METHODS: Thirty-one participants with overweight or obesity followed a 5-week very-low-calorie diet (500 kcal/d) with a subsequent 4-week weight-stable diet (WS), and then an uncontrolled 9-month follow-up. Adipose tissue biopsies were collected for microarray analysis. A correlation and interaction analysis was performed with the weight regain percentage (WR%) ([weight after follow-up - weight after WS] ÷ weight after WS × 100%) by using two gene sets that were previously defined as "stress-related" (n = 107) and "ECM-related" genes (n = 277). RESULTS: During WS, a coexpression network of 8 stress-related genes and 15 ECM-related genes correlating with WR% could be constructed, with links to multiple biological processes. Interaction analysis between stress- and ECM-related genes revealed that several gene combinations were highly related to weight regain. CONCLUSIONS: Our findings underscore the importance of the connection between stress- and ECM-related genes in the risk for weight regain.


Assuntos
Matriz Extracelular/genética , Obesidade/genética , Sobrepeso/genética , Ganho de Peso/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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