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2.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 145-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538461

RESUMO

Nonsyndromic cleft lip with or without cleft palate is the most common craniofacial anomaly affecting around 1 in 700 live births worldwide. Clefts of the human face can be classified anatomically as cleft palate only (CPO), cleft lip only (CLO), cleft lip and palate (CLP) or a combined group of cleft lip with or without cleft palate (CL/P), based on different in embryologic development. These malformations have some genetic origin, in fact several association studies have been performed to obtain important information about the candidate genes; but more important are gene-environment interactions that play an increasing role in its etiology. Epidemiological studies have shown how environmental factors (alcohol, smoking, drugs), as well as possible gene-environment interactions, play an important role in the onset of the malformation. On the contrary, folic acid intake seems to have a protective effect. In this review, we analyze the role of environmental factors related to onset of cleft.


Assuntos
Fenda Labial/etiologia , Fissura Palatina/etiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Fenda Labial/genética , Fissura Palatina/genética , Ácido Fólico/administração & dosagem , Interação Gene-Ambiente , Humanos , Fumar/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações
3.
Adv Exp Med Biol ; 1193: 229-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368108

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the detoxification of toxic aldehydes, especially acetaldehyde, which is commonly considered as a carcinogen. ALDH2 mutation and impaired enzymatic activity will cause acetaldehyde accumulation and thus participate in the development of cancers. It deserves more attention since around 40% of East Asian population carry the inactive ALDH2 allele. Moreover, the risk for cancers will be even higher when ALDH2 mutation combined with heavy alcohol consumption, suggesting a genetic-environmental interaction in carcinogenesis. This may provide us with a potential target for cancer prevention and treatment.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Interação Gene-Ambiente , Acetaldeído , Carcinogênese , Humanos
5.
Medicine (Baltimore) ; 98(26): e16131, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261535

RESUMO

BACKGROUND: The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. METHODS: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. RESULTS: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). CONCLUSION: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Seguimentos , Expressão Gênica , Interação Gene-Ambiente , Estudos de Associação Genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
6.
DNA Cell Biol ; 38(8): 814-823, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31314552

RESUMO

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723, p = 0.031 and adjusted OR = 1.450, 95% CI = 1.112-1.890, p = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105-3.138, p = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354-3.769, p = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078-1.719, p = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122-1.745, p = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Estudos de Casos e Controles , Culinária , Estudos Cross-Over , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Fumar
7.
Nature ; 571(7766): 489-499, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31341302

RESUMO

Epigenetic research has accelerated rapidly in the twenty-first century, generating justified excitement and hope, but also a degree of hype. Here we review how the field has evolved over the last few decades and reflect on some of the recent advances that are changing our understanding of biology. We discuss the interplay between epigenetics and DNA sequence variation as well as the implications of epigenetics for cellular memory and plasticity. We consider the effects of the environment and both intergenerational and transgenerational epigenetic inheritance on biology, disease and evolution. Finally, we present some new frontiers in epigenetics with implications for human health.


Assuntos
Doença/genética , Epigênese Genética/genética , Epigenômica/tendências , Interação Gene-Ambiente , Envelhecimento/genética , Animais , Cromatina/genética , Cromatina/metabolismo , Metilação de DNA/genética , Variação Genética/genética , Humanos , Neoplasias/genética
8.
Plant Dis ; 103(9): 2204-2211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31355735

RESUMO

One hundred and one rice genotypes were evaluated for response to sheath blight disease under greenhouse and lowland irrigated field conditions in Guyana. The level of resistance varied from highly resistant to resistant in 14 genotypes over five experimental trials. These genotypes were also observed with low area under the disease progress curve values and slow blighting reactions against artificial inoculation of the pathogen. Genotypes GR1568-31-9-1-1-2-1 and cultivar Rustic had susceptible reactions in all experiments. Additive main effect and multiplicative interaction analysis was used to study the genotype and environment interactions. The analysis revealed that 52.98% of the total sum of square was attributed to genotype effect, 7.50% was attributable to environment effect, and 39.52% was attributable to genotype by environment interaction (G × E) effects. The G × E was almost as large as the genotype effect, thus indicating significant differences of genotypes across the testing environments. This revealed that resistance was slightly influenced by the G × E. The genotypes that showed stable resistance in all environments in this study could be used for breeding the sheath blight resistance in rice.


Assuntos
Resistência à Doença , Interação Gene-Ambiente , Modelos Estatísticos , Oryza , Cruzamento , Resistência à Doença/genética , Fungos/fisiologia , Genótipo , Guiana , Oryza/genética , Oryza/microbiologia
9.
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
10.
Nat Commun ; 10(1): 2548, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186427

RESUMO

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.


Assuntos
Metilação de DNA/genética , DNA/sangue , Interação Gene-Ambiente , Estudos de Coortes , Epigênese Genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
11.
Gene ; 707: 30-35, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31055022

RESUMO

BACKGROUND: Alcohol intake and tobacco smoking have significant negative health consequences and both are influenced by genetic predispositions. Some studies suggest that the FTO gene is associated with alcohol consumption. We investigated whether a tagging variant (rs17817449) within the FTO gene is associated with alcohol intake, problem drinking and smoking behaviour. METHODS: We analysed data from 26,792 Caucasian adults (47.2% of males; mean age 58.9 (±7.3) years), examined through the prospective cohort HAPIEE study. The primary outcomes were daily alcohol consumption, binge drinking, problem drinking (CAGE score 2+) and smoking status in relation to tagging variants within the FTO and ADH1B genes. RESULTS: We found no significant association of the FTO polymorphism with smoking status in either sex. The associations of the FTO polymorphism with drinking pattern were inconsistent and differed by gender. In men, GG homozygote carriers had lower odds of problem drinking (OR 0.85, 95% CI 0.75-0.96, p = 0.03). In women, the combination of the FTO/ADH1B GG/+A genotypes doubled the risk of binge drinking (OR 2.10, 95% CI 1.19-3.71, p < 0.05), and the risk was further increased among smoking women (OR 4.10, 95% CI 1.64-10.24, p = 0.008). CONCLUSIONS: In this large population study, the FTO gene appeared associated with binge and problem drinking, and the associations were modified by sex, smoking status and the ADH1B polymorphism.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Bebedeira/genética , Polimorfismo de Nucleotídeo Único , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Fumar/genética
12.
BMC Plant Biol ; 19(1): 174, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046677

RESUMO

BACKGROUND: Senescence affects the quality and yield of plants by regulating different traits of plants. A few members of S40 gene family, the barley HvS40 and the Arabidopsis AtS40-3, have been shown to play a role in leaf senescence in Barley and Arabidopsis. Although we previously reported that S40 family exist in most of plants, up to now, no more function of S40 members in plant has been demonstrated. The aim of this study was to provide the senescence related information of S40 gene family in rice as rice is a major crop that feeds about half of the human population in the world. RESULTS: A total of 16 OsS40 genes were identified from the genome database of Oryza sativa L. japonica by bioinformatics analysis. Phylogenetic analysis reveals that the 16 OsS40 proteins are classified into five groups, and 4 of the 16 members belong to group I to which also the HvS40 and AtS40-3 is assigned. S40 genes of rice show high structural similarities, as 13 out of the 16 genes have no intron and the other 3 genes have only 1 or 2 introns. The expression patterns of OsS40 genes were analyzed during natural as well as stress-induced leaf senescence in correspondence with senescence marker genes. We found that 6 of them displayed differential but clearly up-regulated transcript profiles under diverse situations of senescence, including darkness, nitrogen deficiency, hormone treatments as well as pathogen infection. Furthermore, three OsS40 proteins were identified as nuclear located proteins by transient protoplast transformation assay. CONCLUSIONS: Taking all findings together, we concluded that OsS40-1, OsS40-2, OsS40-12 and OsS40-14 genes have potential regulatory function of crosstalk among abiotic, biotic and developmental senescence in rice. Our results provide valuable baseline for functional validation studies of the rice S40 genes in rice leaf senescence.


Assuntos
Oryza/fisiologia , Folhas de Planta/fisiologia , Proteínas de Plantas/fisiologia , Envelhecimento , Interação Gene-Ambiente , Genes de Plantas , Oryza/genética , Folhas de Planta/genética , Proteínas Ribossômicas
13.
Nat Genet ; 51(6): 952-956, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31110353

RESUMO

The development of germplasm adapted to changing climate is required to ensure food security1,2. Genomic prediction is a powerful tool to evaluate many genotypes but performs poorly in contrasting environmental scenarios3-7 (genotype × environment interaction), in spite of promising results for flowering time8. New avenues are opened by the development of sensor networks for environmental characterization in thousands of fields9,10. We present a new strategy for germplasm evaluation under genotype × environment interaction. Yield was dissected in grain weight and number and genotype × environment interaction in these components was modeled as genotypic sensitivity to environmental drivers. Environments were characterized using genotype-specific indices computed from sensor data in each field and the progression of phenology calibrated for each genotype on a phenotyping platform. A whole-genome regression approach for the genotypic sensitivities led to accurate prediction of yield under genotype × environment interaction in a wide range of environmental scenarios, outperforming a benchmark approach.


Assuntos
Agricultura , Meio Ambiente , Genoma de Planta , Genômica , Fenótipo , Zea mays/genética , Grão Comestível , Europa (Continente) , Interação Gene-Ambiente , Estudos de Associação Genética , Genômica/métodos , Geografia
14.
Dis Markers ; 2019: 8062397, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061683

RESUMO

Recent research has shown that prenatal famine exposure may be one of the risk factors for schizophrenia and that people born in famine years may be at an increased risk of schizophrenia due to alteration of the DNA methylation of genes. In this study, the association of rs2283291/rs4648635 and the incidence of schizophrenia and prenatal famine exposure at the genetic level were investigated to provide clues to the pathogenesis of schizophrenia. A total of 960 participants were recruited, comprising 473 prenatal famine-exposed individuals (225 patients and 248 controls) and 487 prenatal non-famine-exposed individuals (220 patients and 267 controls). The association of prenatal famine, schizophrenia, and their interaction with DNA methylation levels was analyzed using SPSS and GMDR software. Gender stratification analysis revealed a significant association between the rs2283291 genotype and schizophrenia in male patients (P = 0.017), and difference still existed after correction by the Bonferroni method. It was also found that an increasing risk of schizophrenia was associated with rs2283291 in males (OR: 1.62, 95% CI: 1.13-2.33, P = 0.0086, AIC = 669.7) in an overdominant model. The results of gene-environment interaction and gene-gene interaction revealed no association with the risk of schizophrenia. This study reported for the first time that rs2283291 was associated with schizophrenia in Chinese males.


Assuntos
Canais de Cálcio Tipo L/genética , Desnutrição/epidemiologia , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , China , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/epidemiologia , Fatores Sexuais
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(5): 480-485, 2019 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-31091605

RESUMO

Objective: To explore the association of TBX5 polymorphisms and environmental exposure index with susceptibility to oral cancer. Methods: A case-control study was conducted to collect 300 oral cancer patients hospitalized in the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University from September 2010 to December 2016. A total of 445 non-tumor patients were selected as the control group. Questionnaires were used to collect the information of all subjects and 5 ml peripheral blood was collected to detect single nucleotide polymorphisms (SNPs) of the rs10492336 locus of TBX5 gene. According to the environmental exposure index score, subjects were divided into two groups, low risk group (0-2.31) and high risk group (2.32-11.76). To analyze the association of TBX5 gene rs10492336 SNPs, environmental exposure index and oral cancer and its interactions. Results: The age of all subjects in the case group and control group were (56.19±13.10) years and (54.56±12.48) years old. Compared with CC genotype, the OR (95%CI) values of the co-dominant genetic model AC genotype and the dominant genetic model AC+AA genotype were 0.69 (0.49-0.98) and 0.70 (0.51-0.97), respectively. Compared with the low risk group, the OR (95%CI) risk of oral cancer in the high risk group was 3.72 (2.55-5.43). The results of gene-environment interaction analysis showed that compared with the group with CC genotype and high risk of environmental exposure index, the OR (95%CI) value of oral cancer in the group with AC+AA genotype and low risk of environmental exposure index was 0.18(0.10-0.31). Furthermore there was a multiplicative interaction between rs10492336 SNPs and environmental exposure index (ß=-0.405, P<0.001). Conclusion: This study suggests that the TBX5 gene rs10492336 SNPs and environmental exposure index were associated with oral cancer. And there was a multiplication interaction between rs10492336 SNPs and environmental exposure index.


Assuntos
Exposição Ambiental/efeitos adversos , Interação Gene-Ambiente , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Adulto , Idoso , Estudos de Casos e Controles , Genótipo , Humanos , Pessoa de Meia-Idade
16.
Microb Pathog ; 133: 103544, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121270

RESUMO

Interleukin-10 (IL-10) is an anti-inflammatory cytokine associated with the inhibition of HIV replication. IL-10 polymorphisms were found to be linked to drug-induced hepatotoxicity. Hence we examined the prevalence of IL-10 (-819C/T,-1082A/G) polymorphisms in a total of 165 HIV patients which included 34 patients with hepatotoxicity, 131 without hepatotoxicity and 155 healthy controls by the PCR-RFLP method. In HIV patients with hepatotoxicity, the IL-10-819TT genotype increased the risk of ARV associated hepatotoxicity severity (OR = 1.61, P = 0.35). IL-10-819TT genotype was overrepresented in patients with hepatotoxicity as compared to healthy controls (26.5% vs. 13.5%, OR = 1.61, P = 0.46). IL-10 -819CT genotype was associated with advance HIV disease stage (OR = 0.49, P = 0.045). In HIV patients without hepatotoxicity, the IL-10-819TT genotype was more prevalent in patients consuming tobacco as compared to non-users (OR = 1.60, P = 0.41). In HIV patients without hepatotoxicity using both alcohol + efavirenz along with IL-10 -819CT genotype resulted in increased risk for the acquisition of ARV associated hepatotoxicity (OR = 4.00, P = 0.36). In multivariate logistic regression, taking nevirapine was associated with the risk hepatotoxicity severity (OR = 0.23, P = 0.005). In conclusion, an insignificant association between IL-10 polymorphisms and susceptibility to ARV associated hepatotoxicity.


Assuntos
Antirretrovirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Predisposição Genética para Doença , Infecções por HIV/complicações , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas , Benzoxazinas/uso terapêutico , Estudos de Casos e Controles , Citocinas , Suscetibilidade a Doenças , Epistasia Genética , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Análise de Regressão , Fatores de Risco , Índice de Gravidade de Doença , Uso de Tabaco
17.
PLoS Comput Biol ; 15(4): e1006445, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31002665

RESUMO

Genetic spaces are often described in terms of fitness landscapes or genotype-to-phenotype maps, where each genetic sequence is associated with phenotypic properties and linked to other genotypes that are a single mutational step away. The positions close to a genotype make up its "mutational landscape" and, in aggregate, determine the short-term evolutionary potential of a population. Populations with wider ranges of phenotypes in their mutational neighborhood are known to be more evolvable. Likewise, those with fewer phenotypic changes available in their local neighborhoods are more mutationally robust. Here, we examine whether forces that change the distribution of phenotypes available by mutation profoundly alter subsequent evolutionary dynamics. We compare evolved populations of digital organisms that were subject to either static or cyclically-changing environments. For each of these, we examine diversity of the phenotypes that are produced through mutations in order to characterize the local genotype-phenotype map. We demonstrate that environmental change can push populations toward more evolvable mutational landscapes where many alternate phenotypes are available, though purely deleterious mutations remain suppressed. Further, we show that populations in environments with harsh changes switch phenotypes more readily than those in environments with more benign changes. We trace this effect to repeated population bottlenecks in the harsh environments, which result in shorter coalescence times and keep populations in regions of the mutational landscape where the phenotypic shifts in question are more likely to occur. Typically, static environments select solely for immediate optimization, at the expensive of long-term evolvability. In contrast, we show that with changing environments, short-term pressures to deal with immediate challenges can align with long-term pressures to explore a more productive portion of the mutational landscape.


Assuntos
Variação Biológica da População , Interação Gene-Ambiente , Modelos Genéticos , Biologia Computacional , Simulação por Computador , Meio Ambiente , Evolução Molecular , Aptidão Genética , Genética Populacional , Mutação , Filogenia , Software
18.
Plant Sci ; 282: 23-39, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31003609

RESUMO

New types of phenotyping tools generate large amounts of data on many aspects of plant physiology and morphology with high spatial and temporal resolution. These new phenotyping data are potentially useful to improve understanding and prediction of complex traits, like yield, that are characterized by strong environmental context dependencies, i.e., genotype by environment interactions. For an evaluation of the utility of new phenotyping information, we will look at how this information can be incorporated in different classes of genotype-to-phenotype (G2P) models. G2P models predict phenotypic traits as functions of genotypic and environmental inputs. In the last decade, access to high-density single nucleotide polymorphism markers (SNPs) and sequence information has boosted the development of a class of G2P models called genomic prediction models that predict phenotypes from genome wide marker profiles. The challenge now is to build G2P models that incorporate simultaneously extensive genomic information alongside with new phenotypic information. Beyond the modification of existing G2P models, new G2P paradigms are required. We present candidate G2P models for the integration of genomic and new phenotyping information and illustrate their use in examples. Special attention will be given to the modelling of genotype by environment interactions. The G2P models provide a framework for model based phenotyping and the evaluation of the utility of phenotyping information in the context of breeding programs.


Assuntos
Genoma de Planta/genética , Melhoramento Vegetal , Interação Gene-Ambiente , Genômica/métodos , Genótipo , Fenótipo , Seleção Genética
19.
Hum Genet ; 138(6): 547-561, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968250

RESUMO

Air pollution is recognized as causal factor for cardiovascular disease (CVD) and is associated with multiple CVD risk factors. Substantial research effort has been invested in understanding the linkages between genetic variation and CVD risk, resulting in over 50 CVD-associated genetic loci. More recently, gene-air pollution interaction studies have quantified the contribution of genetic variation to inter-individual heterogeneity in air pollution health risks, and aided in elucidating mechanisms of air pollution exposure health risks. Here, we perform a comprehensive review of gene-air pollution interaction studies for CVD, as well as risk factors and emerging CVD biomarkers. The literature review revealed that most published interaction studies have been candidate gene studies, causing observed interactions to cluster in a few genes related to detoxification (GSTM1 and GSTT1), inflammation (IL-6), iron processing (HFE), and microRNA processing (GEMIN4 and DGCR8). There have been a few genome-wide interaction studies with results indicating that interactions extend beyond commonly considered genetic loci. Gene-air pollution interactions are observed for exposure periods ranging from hours to years and a variety of air pollutants including particulate matter, gaseous pollutants, and pollutant sources such as traffic. Though the existing evidence for the existence of relevant gene-air pollution interactions for CVD outcomes is substantial, it could be strengthened by improved replication and meta-analyses as well as functional validation.


Assuntos
Poluição do Ar , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Exposição Ambiental/efeitos adversos , Interação Gene-Ambiente , Saúde Ambiental/métodos , Predisposição Genética para Doença/etiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Medição de Risco/métodos , Fatores de Risco
20.
Perspect Biol Med ; 62(1): 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31031294

RESUMO

New techniques have made genome modification cheaper, easier, and faster, leading to a boom in research, especially for biomedical uses. Given the scope and potential power of this research and its applications, people need accurate information about what is being done or proposed, and why, and what the social and political implications might be. Metaphors can be useful in explaining complex topics, as they present the new in terms of the familiar. However, they can also misrepresent both how genomes and bodies work and the social and political implications of research and applications. Existing research shows that this is happening and that we need new language. However, it is not always easy to decide whether an alternative does rhetorical work that will empower publics, patients, biologists, and physicians alike. This article offers a conceptual framework for developing, analyzing, critiquing, and choosing new metaphors that will help improve communication about genomes and genomic research.


Assuntos
Genômica , Metáfora , Pareamento de Bases , DNA , Interação Gene-Ambiente , Genes , Genoma , Humanos , Proteínas/genética
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