RESUMO
BACKGROUND: Cultivated soybean (Glycine max) is a major agricultural crop that provides a crucial source of edible protein and oil. Decreased amounts of saturated palmitic acid and increased amounts of unsaturated oleic acid in soybean oil are considered optimal for human cardiovascular health and therefore there has considerable interest by breeders in discovering genes affecting the relative concentrations of these fatty acids. Using a genome-wide association (GWA) approach with nearly 30,000 single nucleotide polymorphisms (SNPs), we investigated the genetic basis of protein, oil and all five fatty acid levels in seeds from a sample of 570 wild soybeans (Glycine soja), the progenitor of domesticated soybean, to identify quantitative trait loci (QTLs) affecting these seed composition traits. RESULTS: We discovered 29 SNPs located on ten different chromosomes that are significantly associated with the seven seed composition traits in our wild soybean sample. Eight SNPs co-localized with QTLs previously uncovered in linkage or association mapping studies conducted with cultivated soybean samples, while the remaining SNPs appeared to be in novel locations. Twenty-four of the SNPs significantly associated with fatty acid variation, with the majority located on chromosomes 14 (6 SNPs) and seven (8 SNPs). Two SNPs were common for two or more fatty acids, suggesting loci with pleiotropic effects. We also identified some candidate genes that are involved in fatty acid metabolism and regulation. For each of the seven traits, most of the SNPs produced differences between the average phenotypic values of the two homozygotes of about one-half standard deviation and contributed over 3% of their total variability. CONCLUSIONS: This is the first GWA study conducted on seed composition traits solely in wild soybean populations, and a number of QTLs were found that have not been previously discovered. Some of these may be useful to breeders who select for increased protein/oil content or altered fatty acid ratios in the seeds. The results also provide additional insight into the genetic architecture of these traits in a large sample of wild soybean, and suggest some new candidate genes whose molecular effects on these traits need to be further studied.
Assuntos
Genoma de Planta , Estudo de Associação Genômica Ampla , Glycine max/genética , Característica Quantitativa Herdável , Sementes/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Genes de Plantas , Genótipo , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Sementes/química , Glycine max/químicaRESUMO
Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18â h at <0.1% O2 followed by 1â h of reoxygenation) using hypoxia-tolerant intertidal clams Mercenaria mercenaria and hypoxia-sensitive subtidal scallops Argopecten irradians as models. We also assessed H/R-induced changes in cellular energy balance, oxidative damage and unfolded protein response to determine the potential links between mitochondrial dysfunction and cellular injury. Mitochondrial responses to H/R in scallops strongly resembled those in other hypoxia-sensitive organisms. Exposure to hypoxia followed by reoxygenation led to a strong decrease in the substrate oxidation (SOX) and phosphorylation (PHOS) capacities as well as partial depolarization of mitochondria of scallops. Elevated mRNA expression of a reactive oxygen species-sensitive enzyme aconitase and Lon protease (responsible for degradation of oxidized mitochondrial proteins) during H/R stress was consistent with elevated levels of oxidative stress in mitochondria of scallops. In hypoxia-tolerant clams, mitochondrial SOX capacity was enhanced during hypoxia and continued rising during the first hour of reoxygenation. In both species, the mitochondrial PHOS capacity was suppressed during hypoxia, likely to prevent ATP wastage by the reverse action of FO,F1-ATPase. The PHOS capacity recovered after 1â h of reoxygenation in clams but not in scallops. Compared with scallops, clams showed a greater suppression of energy-consuming processes (such as protein turnover and ion transport) during hypoxia, indicated by inactivation of the translation initiation factor EIF-2α, suppression of 26S proteasome activity and a dramatic decrease in the activity of Na(+)/K(+)-ATPase. The steady-state levels of adenylates were preserved during H/R exposure and AMP-dependent protein kinase was not activated in either species, indicating that the H/R exposure did not lead to severe energy deficiency. Taken together, our findings suggest that mitochondrial reorganizations sustaining high oxidative phosphorylation flux during recovery, combined with the ability to suppress ATP-demanding cellular functions during hypoxia, may contribute to high resilience of clams to H/R stress and help maintain energy homeostasis during frequent H/R cycles in the intertidal zone.
Assuntos
Organismos Aquáticos/fisiologia , Metabolismo Energético , Hipóxia/fisiopatologia , Mercenaria/fisiologia , Mitocôndrias/metabolismo , Pectinidae/fisiologia , Aconitato Hidratase/genética , Aconitato Hidratase/metabolismo , Difosfato de Adenosina/farmacologia , Aerobiose/efeitos dos fármacos , Anaerobiose/efeitos dos fármacos , Animais , Organismos Aquáticos/efeitos dos fármacos , Biomarcadores/metabolismo , Metabolismo Energético/efeitos dos fármacos , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/fisiopatologia , Homeostase/efeitos dos fármacos , Cinética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mercenaria/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/farmacologia , Pectinidae/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Protease La/genética , Protease La/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Prótons , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Descanso/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Estresse Fisiológico/efeitos dos fármacosRESUMO
Glyceollins, a family of phytoalexins elicited in legume species, play crucial roles in environmental stress response (e.g., defending against pathogens) and human health. However, little is known about the genetic basis of glyceollin elicitation. In the present study, we employed a metabolite-based genome-wide association (mGWA) approach to identify candidate genes involved in glyceollin elicitation in genetically diverse and understudied wild soybeans subjected to soybean cyst nematode. In total, eight SNPs on chromosomes 3, 9, 13, 15, and 20 showed significant associations with glyceollin elicitation. Six genes fell into two gene clusters that encode glycosyltransferases in the phenylpropanoid pathway and were physically close to one of the significant SNPs (ss715603454) on chromosome 9. Additionally, transcription factors (TFs) genes such as MYB and WRKY were also found as promising candidate genes within close linkage to significant SNPs on chromosome 9. Notably, four significant SNPs on chromosome 9 show epistasis and a strong signal for selection. The findings describe the genetic foundation of glyceollin biosynthesis in wild soybeans; the identified genes are predicted to play a significant role in glyceollin elicitation regulation in wild soybeans. Additionally, how the epistatic interactions and selection influence glyceollin variation in natural populations deserves further investigation to elucidate the molecular mechanism of glyceollin biosynthesis.
RESUMO
Driven by the recent obesity epidemic, interest in understanding the complex genetic and environmental basis of body weight and composition is great. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G(10) advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study and also measured for four exercise traits prior to death, allowing us to test for pre- and postexercise QTLs as well as QTL-by-diet and QTL-by-exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G(4)) generation. For those replicated QTLs, the confidence intervals were reduced from an average of 19 Mb in the G(4) to 8 Mb in the G(10). Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen.
Assuntos
Composição Corporal/genética , Peso Corporal/genética , Dieta , Condicionamento Físico Animal , Locos de Características Quantitativas/genética , Adiposidade/genética , Animais , Cruzamentos Genéticos , Dieta Hiperlipídica , Feminino , Genótipo , Escore Lod , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de TempoRESUMO
Intertidal bivalves are commonly exposed to multiple stressors including periodic hypoxia, temperature fluctuations and pollution, which can strongly affect energy metabolism. We used top-down control and elasticity analyses to determine the interactive effects of intermittent hypoxia, cadmium (Cd) exposure and acute temperature stress on mitochondria of the eastern oyster Crassostrea virginica. Oysters were acclimated at 20°C for 30 days in the absence or presence of 50 µg l(-1) Cd and then subjected to a long-term hypoxia (6 days at <0.5% O(2) in seawater) followed by normoxic recovery. Mitochondrial function was assessed at the acclimation temperature (20°C), or at elevated temperature (30°C) mimicking acute temperature stress in the intertidal zone. In the absence of Cd or temperature stress, mitochondria of oysters showed high resilience to transient hypoxia. In control oysters at 20°C, hypoxia/reoxygenation induced elevated flux capacity of all three studied mitochondrial subsystems (substrate oxidation, phosphorylation and proton leak) and resulted in a mild depolarization of resting mitochondria. Elevated proton conductance and enhanced capacity of phosphorylation and substrate oxidation subsystems may confer resistance to hypoxia/reoxygenation stress in oyster mitochondria by alleviating production of reactive oxygen species and maintaining high aerobic capacity and ATP synthesis rates during recovery. Exposure to environmental stressors such as Cd and elevated temperatures abolished the putative adaptive responses of the substrate oxidation and phosphorylation subsystems, and strongly enhanced proton leak in mitochondria of oysters subjected to hypoxia/reoxygenation stress. Our findings suggest that Cd exposure and acute temperature stress may lead to the loss of mitochondrial resistance to hypoxia and reoxygenation and thus potentially affect the ability of oysters to survive periodic oxygen deprivation in coastal and estuarine habitats.
Assuntos
Cádmio/toxicidade , Crassostrea/efeitos dos fármacos , Crassostrea/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxigênio/farmacologia , Temperatura , Difosfato de Adenosina/farmacologia , Análise de Variância , Animais , Hipóxia Celular/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Metabolismo Energético , Cinética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Prótons , Estresse Fisiológico/efeitos dos fármacosRESUMO
Cadmium (Cd) is a toxic metal and an important environmental pollutant that can strongly affect mitochondrial function and bioenergetics in animals. We investigated the mechanisms of Cd action on mitochondrial function of a marine mollusk (the eastern oyster Crassostrea virginica) by performing a top-down control analysis of the three major mitochondrial subsystems (substrate oxidation, proton leak, and phosphorylation). Our results showed that the substrate oxidation and proton leak subsystems are the main targets for Cd toxicity in oyster mitochondria. Exposure to 12.5 µM Cd strongly inhibited the substrate oxidation subsystem and stimulated the proton conductance across the inner mitochondrial membrane. Proton conductance was also elevated and substrate oxidation inhibited by Cd in the presence of a mitochondrially targeted antioxidant, MitoVitE, indicating that Cd effects on these subsystems were to a large extent ROS independent. Cd did not affect the kinetics of the phosphorylation system, indicating that it has negligible effects on F1, F(O) ATP synthase and/or the adenine nucleotide transporter in oyster mitochondria. Cd exposure altered the patterns of control over mitochondrial respiration, increasing the degree of control conferred by the substrate oxidation subsystem, especially in resting (state 4) mitochondria. Taken together, these data suggest that Cd-induced decrease of mitochondrial efficiency and ATP production are predominantly driven by the high sensitivity of substrate oxidation and proton leak subsystems to this metal.
Assuntos
Cádmio/farmacologia , Crassostrea/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Antioxidantes/farmacologia , Modelos Animais , Compostos Organofosforados/farmacologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/farmacologiaRESUMO
A number of quantitative trait loci (QTLs) recently have been discovered that affect various activity traits in mice, but their collective impact does not appear to explain the consistently moderate to high heritabilities for these traits. We previously suggested interactions of genes, or epistasis, might account for additional genetic variability of activity, and tested this for the average distance, duration and speed run by mice during a 3 week period. We found abundant evidence for epistasis affecting these traits, although, recognized that epistatic effects may well vary within individuals over time. We therefore conducted a full genome scan for epistatic interactions affecting these traits in each of seven three-day intervals. Our intent was to assess the extent and trends in epistasis affecting these traits in each of the intervals. We discovered a number of epistatic interactions of QTLs that influenced the activity traits in the mice, the majority of which were not previously found and appeared to affect the activity traits (especially distance and speed) primarily in the early or in the late age intervals. The overall impact of epistasis was considerable, its contribution to the total phenotypic variance varying from an average of 22-35% in the three traits across all age intervals. It was concluded that epistasis is more important than single-locus effects of genes on activity traits at specific ages and it is therefore an essential component of the genetic architecture of physical activity.
Assuntos
Epistasia Genética , Atividade Motora/genética , Locos de Características Quantitativas/genética , Animais , Feminino , Pleiotropia Genética , Variação Genética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: In recent years it has become increasingly apparent that physical inactivity can predispose individuals to a host of health problems. While many studies have analyzed the effect of various environmental factors on activity, we know much less about the genetic control of physical activity. Some studies in mice have discovered quantitative trait loci (QTL) influencing various physical activity traits, but mostly have analyzed inter-individual variation rather than variation in activity within individuals over time. We conducted a genome scan to identify QTLs controlling the distance, duration, and time run by mice over seven consecutive three-day intervals in an F2 population created by crossing two inbred strains (C57L/J and C3H/HeJ) that differed widely (average of nearly 300%) in their activity levels. Our objectives were (a) to see if we would find QTLs not originally discovered in a previous investigation that assessed these traits over the entire 21-day period and (b) to see if some of these QTLs discovered might affect the activity traits only in the early or in the late time intervals. RESULTS: This analysis uncovered 39 different QTLs, over half of which were new. Some QTLs affected the activity traits only in the early time intervals and typically exhibited significant dominance effects whereas others affected activity only in the later age intervals and exhibited less dominance. We also analyzed the regression slopes of the activity traits over the intervals, and found several QTLs affecting these traits that generally mapped to unique genomic locations. CONCLUSIONS: It was concluded that the genetic architecture of physical activity in mice is much more complicated than has previously been recognized, and may change considerably depending on the age at which various activity measures are assessed.
Assuntos
Variação Genética , Camundongos/genética , Atividade Motora/genética , Locos de Características Quantitativas , Animais , Genótipo , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Polimorfismo de Nucleotídeo Único , Análise de RegressãoRESUMO
BACKGROUND: Physical activity is beneficial in reducing the weight gain and associated health problems often experienced by individuals as they age, but the association of weight change with physical activity remains complex. We tested for a possible genetic basis for this association between 9-12-week body weight change (WTC) and the distance, duration, and speed voluntarily run by 307 mice in an F2 population produced from an intercross of two inbred strains (C57L/J and C3H/HeJ) that differed dramatically in their physical activity levels. RESULTS: In this population WTC did show the expected negative association with the physical activity traits, but only the phenotypic correlation of WTC with speed (-0.18) reached statistical significance. Using an interval mapping approach with single-nucleotide polymorphism markers, we discovered five (four suggestive and one significant) quantitative trait loci (QTLs) affecting body weight change, only one of which appeared to show pleiotropic effects on the physical activity traits as well. Genome-wide epistasis scans also detected several pairwise interactions of QTLs with pleiotropic effects on WTC and the physical activity traits, but these effects made a significant contribution (51%) only to the covariance of WTC with speed. CONCLUSION: It was concluded that the genetic contribution to the phenotypic association between WTC and the physical activity traits in this population of mice was primarily epistatic in origin, restricted to one measure of physical activity, and could be quite variable among different populations depending on the genetic background, experimental design and traits assessed.
Assuntos
Peso Corporal/genética , Variação Genética , Condicionamento Físico Animal , Locos de Características Quantitativas , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Epistasia Genética , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Polimorfismo de Nucleotídeo Único , Análise de RegressãoRESUMO
BACKGROUND: A sedentary lifestyle is often assumed to lead to increases in body weight and potentially obesity and related diseases but in fact little is known about the genetic association between physical activity and body weight. We tested for such an association between body weight and the distance, duration, and speed voluntarily run by 310 mice from the F2 generation produced from an intercross of two inbred lines that differed dramatically in their physical activity levels. METHODS: We used a conventional interval mapping approach with SNP markers to search for QTLs that affected both body weight and activity traits. We also conducted a genome scan to search for relationship QTLs (relQTLs), or chromosomal regions that affected an activity trait variably depending on the phenotypic value of body weight. RESULTS: We uncovered seven quantitative trait loci (QTLs) affecting body weight, but only one co-localized with another QTL previously found for activity traits. We discovered 19 relQTLs that provided evidence for a genetic (pleiotropic) association of physical activity and body weight. The three genotypes at each of these loci typically exhibited a combination of negative, zero, and positive regressions of the activity traits on body weight, the net effect of which was to produce overall independence of body weight from physical activity. We also demonstrated that the relQTLs produced these varying associations through differential epistatic interactions with a number of other epistatic QTLs throughout the genome. CONCLUSION: It was concluded that individuals with specific combinations of genotypes at the relQTLs and epiQTLs might account for some of the variation typically seen in plots of the association of physical activity with body weight.
Assuntos
Comportamento Animal , Peso Corporal , Variação Genética , Endogamia , Camundongos/fisiologia , Animais , Feminino , Genótipo , Masculino , Camundongos/genética , Atividade Motora , Locos de Características Quantitativas , Característica Quantitativa HerdávelRESUMO
PURPOSE: Isometric handgrip (IHG) training lowers systolic and diastolic blood pressure (SBP and DBP, respectively), but the efficacy of IHG training in cardiopulmonary rehabilitation patients is unknown. The purpose of this study was to determine if IHG decreases blood pressure in cardiopulmonary rehabilitation patients. METHODS: Cardiopulmonary rehabilitation program participants (n = 11; 50-80 yr old) were randomized to IHG (n = 6) or control (CON; no treatment; n = 5) groups. IHG participants completed an IHG training program at 30% maximal voluntary contraction, 3 d/wk for 6 wk. Resting SBP, DBP, and heart rate were assessed weekly. RESULTS: Mean regression for SBP following IHG was negative (-1.04 ± 0.80). Mean regression in the CON group was positive (0.50 ± 0.88), but there was no significant difference between groups. Separate analysis of weeks 1 to 7 yielded a negative mean regression (-1.12 ± 0.54) in the IHG group, but positive (1.2 ± 0.60) in the CON group. A Wilcoxon test of these differences yielded significance for SBP (P = .009). In 3 of 6 IHG participants, SBP was lower (mean ± SD: -16 ± 11 mm Hg; P = .12), and in 2 IHG participants, DBP was lower (-9 ± 1 mm Hg; P = .06) compared with baseline. In 2 of 5 CON participants, SBP was not significantly lower (-11 ± 7 mm Hg) and, in 3 of 5 CON participants, DBP was lower (-7 ± 4 mm Hg; P = .04). CONCLUSIONS: Our data suggest that standard IHG training may be inadequate for blood pressure management immediately following a major cardiac or pulmonary event. Future work with a larger cohort and more developed training protocol to determine the efficacy of IHG training in patients with cardiopulmonary disease is warranted.
Assuntos
Reabilitação Cardíaca/métodos , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Força da Mão/fisiologia , Hipertensão/terapia , Pneumopatias/reabilitação , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Hipertensão/complicações , Pneumopatias/complicações , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
The genomic locations and identities of the genes that regulate voluntary physical activity are presently unknown. The purpose of this study was to search for quantitative trait loci (QTL) that are linked with daily mouse running wheel distance, duration, and speed of exercise. F(2) animals (n = 310) derived from high active C57L/J and low active C3H/HeJ inbred strains were phenotyped for 21 days. After phenotyping, genotyping with a fully informative single-nucleotide polymorphism panel with an average intermarker interval of 13.7 cM was used. On all three activity indexes, sex and strain were significant factors, with the F(2) animals similar to the high active C57L/J mice in both daily exercise distance and duration of exercise. In the F(2) cohort, female mice ran significantly farther, longer, and faster than male mice. QTL analysis revealed no sex-specific QTL but at the 5% experimentwise significance level did identify one QTL for duration, one QTL for distance, and two QTL for speed. The QTL for duration (DUR13.1) and distance (DIST13.1) colocalized with the QTL for speed (SPD13.1). Each of these QTL accounted for approximately 6% of the phenotypic variance, whereas SPD9.1 (chromosome 9, 7 cM) accounted for 11.3% of the phenotypic variation. DUR13.1, DIST13.1, SPD13.1, and SPD9.1 were subsequently replicated by haplotype association mapping. The results of this study suggest a genetic basis of voluntary activity in mice and provide a foundation for future candidate gene studies.
Assuntos
Camundongos/genética , Atividade Motora/genética , Locos de Características Quantitativas , Animais , Cruzamentos Genéticos , Epistasia Genética , Feminino , Genótipo , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos , Fenótipo , Polimorfismo de Nucleotídeo Único , Corrida , Fatores Sexuais , Especificidade da Espécie , Fatores de TempoRESUMO
BACKGROUND: Genomic imprinting is an epigenetic source of variation in quantitative traits that results from monoallelic gene expression, where commonly either only the paternally- or the maternally-derived allele is expressed. Imprinting has been shown to affect a diversity of complex traits in a variety of species. For several such quantitative traits sex-dependent genetic effects have been discovered, but whether imprinting effects also show such sex-dependence has yet to be explored. Moreover, theoretical work on the evolution of sex-dependent genomic imprinting effects makes specific predictions about the phenotypic patterns of such effects, which, however, have not been assessed empirically to date. RESULTS: Using a genome-scan for loci affecting a set of complex growth and body composition traits from an intercross between two divergent mouse strains, we investigated possible sex-dependent imprinting effects. Our results demonstrate for the first time the existence of genomic imprinting effects that depend on sex and are not related to sex-chromosome effects. We detected a total of 13 loci on 11 chromosomes that showed significant differences between the sexes in imprinting effects. Most loci showed imprinting effects in only one sex, with eight imprinted effects found in males and six in females. One locus showed sex-dependent imprinting effects in both sexes for different traits. The absence of an imprinting effect in one sex was not necessarily indicative of the overall inactivity of the locus in that sex, as for several loci a significant additive or dominance effect was detected. Moreover, three loci exhibited significant additive effects in both sexes but their imprinting effect was restricted to one sex. CONCLUSION: Our results clearly show that imprinting effects can be sex-dependent and also suggest that new candidate imprinted loci can be detected when taking account of sex-specific imprinting effects. However, predictions made about the evolution of sex-dependent imprinting effects and associated phenotypic patterns cannot be unequivocally supported at present and further research into the selection pressures applied to the strains of mice used in our study is required.
Assuntos
Variação Genética , Impressão Genômica/genética , Fenótipo , Animais , Peso Corporal/genética , Feminino , Genótipo , Masculino , Camundongos , Locos de Características Quantitativas/genética , Fatores SexuaisRESUMO
The contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant and teratogen that has been shown to alter craniofacial development. Differences in sensitivity to TCDD are attributed primarily to differences in alleles at the Ahr locus coding for the aryl-hydrocarbon receptor (AHR) that binds TCDD and mediates its effects by altering gene expression. The authors used geometric morphometric methods to evaluate differences in the effects of small in utero exposures of TCDD on adult mandible size and shape in five different inbred mouse strains with the same Ahr alleles. Because of the known effects of this toxicant on bone and craniofacial structures, the authors hypothesized that TCDD would decrease mandible size and alter mandible shape, but that the effects of TCDD exposure would differ among the inbred strains. The authors found that TCDD did alter mandible size and shape, but these effects were limited to specific strains and also differed between the sexes. The relative sensitivity to TCDD's effects on mandibles did not correspond with the previously reported sensitivity to TCDD's effects on molars. The authors hypothesize that beyond Ahr-related effects, variation in response to TCDD reflects differences in the genetic architecture controlling the trait being evaluated, thus explaining the species, strain, and trait specificity of TCDD.
Assuntos
Mandíbula/efeitos dos fármacos , Exposição Materna/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/genética , Teratogênicos/toxicidade , Análise de Variância , Animais , Feminino , Predisposição Genética para Doença , Masculino , Mandíbula/crescimento & desenvolvimento , Mandíbula/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Dibenzodioxinas Policloradas/administração & dosagem , GravidezRESUMO
We recently identified several (4-8) quantitative trait loci (QTL) for 3 physical activity traits (daily distance, duration, and speed voluntarily run) in an F(2) population of mice derived from an original intercross of 2 strains that exhibited large differences in activity. These QTL cumulatively explained from 11% to 34% of the variation in these traits, but this was considerably less than their total genetic variability estimated from differences among inbred strains. We therefore decided to test whether epistatic interactions might account for additional genetic variation in these traits in this same population of mice. We conducted a full genome epistasis scan for all possible interactions of QTL between each pair of 20 chromosomes. The results of this scan revealed an abundance of epistasis, with QTL throughout the genome being involved in significant interactions. Overall, epistatic effects contributed an average of 26% of the total variation among the 3 activity traits. These results suggest that epistatic interactions of genes may play as important a role in the genetic architecture of physical activity traits as single-locus effects and need to be considered in future candidate gene identification studies.
Assuntos
Epistasia Genética , Atividade Motora/genética , Animais , Cruzamentos Genéticos , Feminino , Genoma , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Locos de Características QuantitativasRESUMO
Prenatal development is highly sensitive to the effects of environmental contaminants. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant that at very low levels causes teratogenic effects such as irregular tooth development. Variations in susceptibility to TCDD's effects have been attributed primarily to differences at the Ahr locus. There is some evidence, however, that genes at other loci may be involved in mediating TCDD's effects on various endpoints. Our hypothesis therefore was that the effect of TCDD on molar development would differ even among inbred mouse strains possessing similar Ahr alleles. To test this, geometric morphometric techniques were used to evaluate the effects of several different levels of TCDD on molar size, shape and asymmetry in the offspring of dosed females from five different inbred strains of mice bearing TCDD-sensitive Ahr alleles. The results indicated that a maternal dose of 1 microg TCDD/kg body weight on gestation day 13 altered the shape (but not the size or asymmetry) of the first two molars in mice from the C3H/HeJ and CBA/J strains of mice, but not in mice from the other strains. The C3H/HeJ and CBA/J strains appeared to be the most sensitive to the disruption of molar development via TCDD and the C57BL/6J strain appeared to be the least sensitive.
Assuntos
Camundongos Endogâmicos , Dente Molar/crescimento & desenvolvimento , Dibenzodioxinas Policloradas/farmacologia , Receptores de Hidrocarboneto Arílico/genética , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Dente Molar/efeitos dos fármacos , Dibenzodioxinas Policloradas/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Especificidade da EspécieRESUMO
Isometric exercise training (IET)-induced reductions in resting blood pressure (RBP) have been achieved in laboratory environments, but data in support of IET outside the laboratory are scarce. The aim of this study was to compare 12 weeks of home-based (HOM) IET with laboratory-based, face-to-face (LAB) IET in hypertensive adults. Twenty-two hypertensive participants (24-60 years) were randomized to three conditions: HOM, LAB, or control (CON). IET involved isometric handgrip training (4 × 2 minutes at 30% maximum voluntary contraction, 3 days per week). RBP was measured every 6 weeks (0, 6, and 12 weeks) during training and 6 weeks after training (18 weeks). Clinically meaningful, but not statistically significant reductions in RBP were observed after 12 weeks of LAB IET (resting systolic blood pressure [SBP] -9.1 ± 4.1; resting diastolic blood pressure [DBP] -2.8 ± 2.1; P > .05), which was sustained for 6 weeks of detraining (SBP -8.2 ± 2.9; DBP -4 ± 2.9, P > .05). RBP was reduced in the HOM group after 12 weeks of training (SBP -9.7 ± 3.4; DBP -2.2 ± 2.0; P > .05), which was sustained for an additional 6 weeks of detraining (SBP -5.5 ± 3.4; DBP -4.6 ± 1.8; P > .05). Unsupervised home-based IET programs present an exciting opportunity for community-based strategies to combat hypertension, but additional work is needed if IET is to be used routinely outside the laboratory.
RESUMO
The role of genetics in the determination of maximal exercise endurance is unclear. Six- to nine-week-old F2 mice (n = 99; 60 female, 39 male), derived from an intercross of two inbred strains that had previously been phenotyped as having high maximal exercise endurance (Balb/cJ) and low maximal exercise endurance (DBA/2J), were treadmill tested to estimate exercise endurance. Selective genotyping of the F2 cohort (n = 12 high exercise endurance; n = 12 low exercise endurance) identified a significant quantitative trait locus (QTL) on chromosome X (53.7 cM, DXMit121) in the entire cohort and a suggestive QTL on chromosome 8 (36.1 cM, D8Mit359) in the female mice. Fine mapping with the entire F2 cohort and additional informative markers confirmed and narrowed the QTLs. The chromosome 8 QTL (EE8(F)) is homologous with two suggestive human QTLs and one significant rat QTL previously linked with exercise endurance. No effect of sex (P = 0.33) or body weight (P = 0.79) on exercise endurance was found in the F2 cohort. These data indicate that genetic factors in distinct chromosomal regions may affect maximal exercise endurance in the inbred mouse. Whereas multiple genes are located in the identified QTL that could functionally affect exercise endurance, this study serves as a foundation for further investigations delineating the identity of genetic factors influencing maximum exercise endurance.
Assuntos
Ligação Genética , Resistência Física/genética , Locos de Características Quantitativas , Cromossomo X , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Feminino , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Fenótipo , Especificidade da EspécieRESUMO
2,3,7,8-Tetracholorodibenzo-p-dioxin is a highly toxic substance that can cause a variety of adverse effects on organisms. While it has been shown that TCDD acts mainly through the aryl-hydrocarbon receptor (AHR), the mechanism of toxicity is not completely clear. To test the role of the AHR in mediating the effects of TCDD, we exposed two congenic strains of mice differing only at the Ahr locus (Ahr(b)/Ahr(b) and Ahr(d)/Ahr(d)) to TCDD (0, 0.01, 0, or 1 microg/kg body weight) in utero on gestation day 13 and examined the developmental effects on mandible and mandibular tooth row size and shape. Our hypothesis was that TCDD would significantly affect one or more of these endpoints in Ahr(b)/Ahr(b) mice, previously shown to be sensitive to the effects of TCDD, while causing little or no effect in mice carrying the less sensitive Ahr(d) allele. At the doses used in this study, TCDD did not alter the size of mandibles or molars in either Ahr(b)/Ahr(b) or Ahr(d)/Ahr(d) mice. However, we did find that the highest dose of TCDD altered mandible shape, but only in Ahr(b)/Ahr(b) (not Ahr(d)/Ahr(d)) male mice. Similarly, the highest dose of TCDD significantly altered molar shape in Ahr(b)/Ahr(b) but not Ahr(d)/Ahr(d) male mice, although females in both congenic strains were affected. These results suggest that the effects of TCDD on molar and mandible shape are influenced by the Ahr genotype but that males and females differ in sensitivity to both of these effects.
Assuntos
Anormalidades Induzidas por Medicamentos , Poluentes Ambientais/toxicidade , Mandíbula/efeitos dos fármacos , Dente Molar/efeitos dos fármacos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Relação Dose-Resposta a Droga , Feminino , Genótipo , Idade Gestacional , Masculino , Mandíbula/anormalidades , Mandíbula/crescimento & desenvolvimento , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Dente Molar/anormalidades , Dente Molar/crescimento & desenvolvimento , Tamanho do Órgão , Gravidez , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores SexuaisRESUMO
Deleterious effects of climate change and human activities, as well as diverse environmental stresses, present critical challenges to food production and the maintenance of natural diversity. These challenges may be met by the development of novel crop varieties with increased biotic or abiotic resistance that enables them to thrive in marginal lands. However, considering the diverse interactions between crops and environmental factors, it is surprising that evolutionary principles have been underexploited in addressing these food and environmental challenges. Compared with domesticated cultivars, crop wild relatives (CWRs) have been challenged in natural environments for thousands of years and maintain a much higher level of genetic diversity. In this review, we highlight the significance of CWRs for crop improvement by providing examples of CWRs that have been used to increase biotic and abiotic stress resistance/tolerance and overall yield in various crop species. We also discuss the surge of advanced biotechnologies, such as next-generation sequencing technologies and omics, with particular emphasis on how they have facilitated gene discovery in CWRs. We end the review by discussing the available resources and conservation of CWRs, including the urgent need for CWR prioritization and collection to ensure continuous crop improvement for food sustainability.