Distância genética entre linhagens avançadas de germoplasma de algodão com uso de marcadores de RAPD e microssatélites

O objetivo deste trabalho foi selecionar coeficientes de similaridade para serem aplicados a conjuntos de genótipos de algodoeiro com baixa diversidade genética. Analisou-se um conjunto de 65 linhagens e 4 cultivares de algodão, com marcadores de RAPD e SSR, e estimou-se a similaridade genética de acordo com sete coeficientes de similaridade: Coincidência Simples, Rogers & Tanimoto, Ochiai, Hamman, Jaccard, Dice e Russel & Rao. A adequação dos coeficientes ao conjunto de genótipos foi verificada por correlação entre as matrizes de distância, índice de consenso entre os dendrogramas e otimização de Tocher. As análises mostraram que o coeficiente de Russel e Rao foi divergente em relação aos demais e seu uso não é recomendável. Entre os parâmetros usados para avaliar a qualidade de informação de cada coeficiente, apenas o índice de consenso estabeleceu diferenças e os classificou em dois grupos: aquele em que a ausência simultânea é considerada e aquele em que ela é desconsiderada. Considerando-se a presença de apenas dois alelos microssatélites por loco e os maiores índices de consenso, os coeficientes de Coincidência Simples, Hamman e Rogers & Tanimoto devem ser preferidos, quando em conjuntos de genótipos de algodoeiro melhorados e com baixa diversidade.

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.

Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

In situ and genetic characterization of Gossypium barbadense populations from the states of Pará and Amapá, Brazil

The objective of this work was to characterize the populations of Gossypium barbadense in the states of Amapá and Pará, Brazil. In situ characterization was conducted through interviews with the owners of the plants and environmental observations. Leaf or petal tissue as well as seed samples were collected for genetic characterization by single sequence repeats markers and for storage in germplasm banks, respectively. The plants were maintained in dooryards and used mainly for medical purposes. The genetic analysis showed no heterozygous plants at the loci tested (f = 1), indicating that reproduction occurs mainly through selfing. The total genetic diversity was high (He = 0.39); and a high level of differentiation was observed between cotton plants from the two states (F ST = 0.36). Conventional methods of in situ maintenance of G. barbadense populations are not applicable. The conservation of the genetic variability of populations present in the two states could be achieved through germplasm collection and establishing of ex situ seed banks.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Fixação biológica e transferência de nitrogênio por leguminosas em pomar orgânico de mangueira e gravioleira

O objetivo deste trabalho foi avaliar a fixação biológica de nitrogênio (FBN) e a transferência do N derivado da FBN das espécies leguminosas - gliricídia (Gliricidia sepium), crotalária (Crotalaria juncea) e feijão-guandu anão (Cajanus cajan) - para um pomar orgânico de mangueira e gravioleira, pelo método da abundância natural de N. Foram avaliados os seguintes sistemas de cultivos consorciados: mangueira e gravioleira com gliricídia; mangueira e gravioleira com crotalária; mangueira e gravioleira com feijão-guandu; e a testemunha mangueira e gravioleira. Agliricídia apresentou maior potencial de FBN (80%), seguida da crotalária (64,5%) e feijão-guandu (45%). Em dois cortes, a crotalária forneceu 149,5 kg ha-1 por ano de N, com 96,5kg derivados da FBN. A gliricídia com três podas anuais forneceu 56,4 e 80,3 kg ha-1 por ano de N, com 45 e 64 kg derivados da FBN, em dois anos consecutivos. A quantidade de N fornecida foi superior à demandada pela mangueira e gravioleira. Variações na abundância natural de 15N foram detectadas somente na gravioleira. Gliricídia e crotalária destacaram-se na transferência de N, com cerca de 22,5 e 40% do N fixado, respectivamente. A adubação verde com gliricídia possibilita o parcelamento do N, com melhor aproveitamento pelas espécies frutíferas.

The peroxisome proliferator-activated receptor (PPAR) β/δ agonist GW501516 inhibits IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation and insulin resistance in human liver cells.

AIM/HYPOTHESIS: IL-6 induces insulin resistance by activating signal transducer and activator of transcription 3 (STAT3) and upregulating the transcription of its target gene SOCS3. Here we examined whether the peroxisome proliferator-activated receptor (PPAR)β/δ agonist GW501516 prevented activation of the IL-6-STAT3-suppressor of cytokine signalling 3 (SOCS3) pathway and insulin resistance in human hepatic HepG2 cells. METHODS: Studies were conducted with human HepG2 cells and livers from mice null for Pparβ/δ (also known as Ppard) and wild-type mice. RESULTS: GW501516 prevented IL-6-dependent reduction in insulin-stimulated v-akt murine thymoma viral oncogene homologue 1 (AKT) phosphorylation and in IRS-1 and IRS-2 protein levels. In addition, treatment with this drug abolished IL-6-induced STAT3 phosphorylation of Tyr⁷⁰⁵ and Ser⁷²⁷ and prevented the increase in SOCS3 caused by this cytokine. Moreover, GW501516 prevented IL-6-dependent induction of extracellular-related kinase 1/2 (ERK1/2), a serine-threonine protein kinase involved in serine STAT3 phosphorylation; the livers of Pparβ/δ-null mice showed increased Tyr⁷⁰⁵- and Ser⁷²⁷-STAT3 as well as phospho-ERK1/2 levels. Furthermore, drug treatment prevented the IL-6-dependent reduction in phosphorylated AMP-activated protein kinase (AMPK), a kinase reported to inhibit STAT3 phosphorylation on Tyr⁷⁰⁵. In agreement with the recovery in phospho-AMPK levels observed following GW501516 treatment, this drug increased the AMP/ATP ratio and decreased the ATP/ADP ratio. CONCLUSIONS/INTERPRETATION: Overall, our findings show that the PPARβ/δ activator GW501516 prevents IL-6-induced STAT3 activation by inhibiting ERK1/2 phosphorylation and preventing the reduction in phospho-AMPK levels. These effects of GW501516 may contribute to the prevention of cytokine-induced insulin resistance in hepatic cells.

Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosus

Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Análise espacial dos fatores da equação universal de perda de solo em área de nascentes

O objetivo deste trabalho foi avaliar a perda de solo de área de nascentes da Microbacia do Córrego do Tijuco, SP. Foi utilizada a análise espacial dos fatores da equação universal da perda de solo (EUPS), em integração com análise de componentes principais e geoestatística. A perda de solo média, estimada para a área, foi de 118,5 Mg ha‑1 por ano, considerada alta. Próximo à zona urbana, houve alta interação dos fatores erosividade da chuva e práticas conservacionistas, o que evidencia grande perda de solo, em razão da concentração da água proveniente da camada impermeabilizada urbana, com alta velocidade de escoamento. Nos divisores de águas, a atuação da erodibilidade foi proeminente, em contraste com o fator topográfico. Foram observadas áreas com atuação conjunta destes fatores, inclusive em locais de inclinação suave, porém com alto potencial natural de erosão. A interação das análises multivariadas e geoestatística permite a estratificação da área, identifica locais com propriedades específicas quanto à perda de solo, e espacializa os fatores do processo erosivo e suas interações ao longo do relevo.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

Metodologia para análise de adaptabilidade e estabilidade por meio de regressão quantílica

O objetivo deste trabalho foi desenvolver e validar uma metodologia de análise da adaptabilidade e da estabilidade fenotípica baseada em regressão quantílica (RQ). Para tanto, foram simulados valores fenotípicos com distribuição simétrica e com distribuição assimétrica à direita e à esquerda, com ou sem a presença de "outliers". A metodologia proposta foi aplicada a um conjunto de dados provenientes de um experimento com 92 genótipos de alfafa (Medicago sativa), avaliados em 20 ambientes, e comparada às metodologias de Eberhart & Russell e de regressão não paramétrica. A metodologia da RQ proporcionou resultados iguais ou superiores aos obtidos com as metodologias alternativas avaliadas. No entanto, a ocorrência de resultados discordantes entre as metodologias evidencia a importância de se avaliar a simetria na distribuição dos valores fenotípicos. Para distribuições simétricas, na presença de "outliers", deve-se utilizar a RQ com valor de quantil estimado (τ) em 0,50; na ausência de "outliers", pode-se utilizar tanto a metodologia de Eberhart & Russell quanto a RQ (τ = 0,50). Para distribuições assimétricas, indica-se o uso da RQ com τ = 0,25, para assimetria à direita, e com τ = 0,75, para assimetria à esquerda, independentemente da presença de "outliers".

Optimal use of SSR markers for varietal identification of upland cotton

Abstract: The objective of this work was to identify polymorphic simple sequence repeat (SSR) markers for varietal identification of cotton and evaluation of the genetic distance among the varieties. Initially, 92 SSR markers were genotyped in 20 Brazilian cotton cultivars. Of this total, 38 loci were polymorphic, two of which were amplified by one primer pair; the mean number of alleles per locus was 2.2. The values of polymorphic information content (PIC) and discrimination power (DP) were, on average, 0.374 and 0.433, respectively. The mean genetic distance was 0.397 (minimum of 0.092 and maximum of 0.641). A panel of 96 varieties originating from different regions of the world was assessed by 21 polymorphic loci derived from 17 selected primer pairs. Among these varieties, the mean genetic distance was 0.387 (minimum of 0 and maximum of 0.786). The dendrograms generated by the unweighted pair group method with arithmetic average (UPGMA) did not reflect the regions of Brazil (20 genotypes) or around the world (96 genotypes), where the varieties or lines were selected. Bootstrap resampling shows that genotype identification is viable with 19 loci. The polymorphic markers evaluated are useful to perform varietal identification in a large panel of cotton varieties and may be applied in studies of the species diversity.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Perspectiva bayesiana na seleção de genótipos de feijão-caupi em ensaios de valor de cultivo e uso

Resumo:O objetivo deste trabalho foi selecionar, sob a perspectiva bayesiana, genótipos de feijão-caupi (Vigna unguiculata) que reúnam alta adaptabilidade e estabilidade fenotípicas, no Estado do Mato Grosso do Sul. Foram utilizados dados de quatro experimentos, conduzidos em delineamento de blocos ao acaso, em que a produtividade de grãos de 20 genótipos de feijão-caupi semiprostrado foi avaliada. Para representar as distribuições a priori pouco informativas, utilizaram-se distribuições de probabilidade com grande variância; e, para representar distribuições a priori informativas, adotou-se o conceito de metanálise, com uso de informações de trabalhos anteriores. A comparação entre as distribuições a priori foi realizada por meio do fator de Bayes. A abordagem bayesiana proporciona maior acurácia na seleção de genótipos de feijão-caupi semiprostrado, com elevadas adaptabilidade e estabilidade fenotípicas avaliadas por meio da metodologia de Eberhart & Russell. Com base nas prioris informativas, os genótipos MNC99-507G-4, TE97-309G-24, MNC99-542F-7 e BR 17-Gurguéia são classificados como de alta adaptabilidade a ambientes favoráveis. Já os genótipos TE96-290-12G, MNC99-510F-16, MNC99-508G-1, MNC99-541F-21, MNC99-542F-5 e MNC99-547F-2 apresentam alta adaptabilidade a ambientes desfavoráveis.