960 resultados para Genetic differences
Resumo:
Neurocysticercosis (NC) is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht), which were clustered in four haplogroups (Hg), were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.
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Arbuscular mycorrhizal fungi (AMF) are important symbionts of plants that improve plant nutrient acquisition and promote plant diversity. Although within-species genetic differences among AMF have been shown to differentially affect plant growth, very little is actually known about the degree of genetic diversity in AMF populations. This is largely because of difficulties in isolation and cultivation of the fungi in a clean system allowing reliable genotyping to be performed. A population of the arbuscular mycorrhizal fungus Glomus intraradices growing in an in vitro cultivation system was studied using newly developed simple sequence repeat (SSR), nuclear gene intron and mitochondrial ribosomal gene intron markers. The markers revealed a strong differentiation at the nuclear and mitochondrial level among isolates. Genotypes were nonrandomly distributed among four plots showing genetic subdivisions in the field. Meanwhile, identical genotypes were found in geographically distant locations. AMF genotypes showed significant preferences to different host plant species (Glycine max, Helianthus annuus and Allium porrum) used before the fungal in vitro culture establishment. Host plants in a field could provide a heterogeneous environment favouring certain genotypes. Such preferences may partly explain within-population patterns of genetic diversity.
Resumo:
The species Formica aquilonia and F. lugubris of the mound-building red wood ants have a disjunct boreoalpine distribution in Europe. The populations of F. aquilonia in Finland, Switzerland and the British Isles show little genetic differentiation, whereas the populations of F. lugubris show considerable differentiation. The Central European populations morphologically identified as F. lugubris can be genetically divided into two groups (here called types A and B). Type B is found in the Alps and the Jura mountains, and is genetically inseparable from F. aquilonia. Type A lives sympatrically with type B in the Jura mountains and is also found in the British Isles. Sympatry of the two types in the Jura shows that these are separate species. It remains open whether type B is morphologically atypical F. aquilonia or whether it is a separate species, perhaps with a past history of introgression between F. aquilonia and F. lugubris. The gene frequencies in the Finnish populations of F. lugubris differ from those of both types A and B. Genetic differences within F. lugubris indicate that the populations have evolved separately for a long time. The social structure of F. lugubris colonies also shows geographic variation. The nests in Finland and the British Isles seem to be mainly monogynous and monodomous, whereas the nests in Central Europe are polygynous and form polydomous colonies. F. aquilonia has polygynous and polydomous colonies in all populations studied.
Resumo:
Sleep deprivation (SD) results in increased electroencephalographic (EEG) delta power during subsequent non-rapid eye movement sleep (NREMS) and is associated with changes in the expression of circadian clock-related genes in the cerebral cortex. The increase of NREMS delta power as a function of previous wake duration varies among inbred mouse strains. We sought to determine whether SD-dependent changes in circadian clock gene expression parallel this strain difference described previously at the EEG level. The effects of enforced wakefulness of incremental durations of up to 6 h on the expression of circadian clock genes (bmal1, clock, cry1, cry2, csnk1epsilon, npas2, per1, and per2) were assessed in AKR/J, C57BL/6J, and DBA/2J mice, three strains that exhibit distinct EEG responses to SD. Cortical expression of clock genes subsequent to SD was proportional to the increase in delta power that occurs in inbred strains: the strain that exhibits the most robust EEG response to SD (AKR/J) exhibited dramatic increases in expression of bmal1, clock, cry2, csnkIepsilon, and npas2, whereas the strain with the least robust response to SD (DBA/2) exhibited either no change or a decrease in expression of these genes and cry1. The effect of SD on circadian clock gene expression was maintained in mice in which both of the cryptochrome genes were genetically inactivated. cry1 and cry2 appear to be redundant in sleep regulation as elimination of either of these genes did not result in a significant deficit in sleep homeostasis. These data demonstrate transcriptional regulatory correlates to previously described strain differences at the EEG level and raise the possibility that genetic differences underlying circadian clock gene expression may drive the EEG differences among these strains.
Resumo:
Arbuscular mycorrhizal fungi (AMF) are ecologically important root symbionts of most terrestrial plants. Ecological studies of AMF have concentrated on differences between species; largely assuming little variability within AMF species. Although AMF are clonal, they have evolved to contain a surprisingly high within-species genetic variability, and genetically different nuclei can coexist within individual spores. These traits could potentially lead to within-population genetic variation, causing differences in physiology and symbiotic function in AMF populations, a consequence that has been largely neglected. We found highly significant genetic and phenotypic variation among isolates of a population of Glomus intraradices but relatively low total observed genetic diversity. Because we maintained the isolated population in a constant environment, phenotypic variation can be considered as variation in quantitative genetic traits. In view of the large genetic differences among isolates by randomly sampling two individual spores, <50% of the total observed population genetic diversity is represented. Adding an isolate from a distant population did not increase total observed genetic diversity. Genetic variation exceeded variation in quantitative genetic traits, indicating that selection acted on the population to retain similar traits, which might be because of the multigenomic nature of AMF, where considerable genetic redundancy could buffer the effects of changes in the genetic content of phenotypic traits. These results have direct implications for ecological research and for studying AMF genes, improving commercial AMF inoculum, and understanding evolutionary mechanisms in multigenomic organisms.
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In their invasive ranges, Argentine ant populations often form one geographically vast supercolony, genetically and chemically uniform within which there is no intraspecific aggression. Here we present regional patterns of intraspecific aggression, cuticular hydrocarbons (CHCs) and population genetics of 18 nesting sites across Corsica and the French mainland. Aggression tests confirm the presence of a third European supercolony, the Corsican supercolony, which exhibits moderate to high levels of aggression, depending on nesting sites, with the Main supercolony, and invariably high levels of aggression with the Catalonian supercolony. The chemical analyses corroborated the behavioural data, with workers of the Corsican supercolony showing moderate differences in CHCs compared to workers of the European Main supercolony and strong differences compared to workers of the Catalonian supercolony. Interestingly, there were also clear genetic differences between workers of the Catalonian supercolony and the two other supercolonies at both nuclear and mitochondrial markers, but only very weak genetic differentiation between nesting sites of the Corsican and Main supercolonies (F(ST) = 0.06). A detailed comparison of the genetic composition of supercolonies also revealed that, if one of the last two supercolonies derived from the other, it is the Main supercolony that derived from the Corsican supercolony rather than the reverse. Overall, these findings highlight the importance of conducting more qualitative and quantitative analyses of the level of aggression between supercolonies, which has to be correlated with genetic and chemical data.
Resumo:
It has been known for some time that different arbuscular mycorrhizal fungal (AMF) taxa confer differences in plant growth. Although genetic variation within AMF species has been given less attention, it could potentially be an ecologically important source of variation. Ongoing studies on variability in AMF genes within Glomus intraradices indicate that at least for some genes, such as the BiP gene, sequence variability can be high, even in coding regions. This suggests that genetic variation within an AMF may not be selectively neutral. This clearly needs to be investigated in more detail for other coding regions of AMF genomes. Similarly, studies on AMF population genetics indicate high genetic variation in AMF populations, and a considerable amount of variation seen in phenotypes in the population can be attributed to genetic differences among the fungi. The existence of high within-species genetic variation could have important consequences for how investigations on AMF gene expression and function are conducted. Furthermore, studies of within-species genetic variability and how it affects variation in plant growth will help to identify at what level of precision ecological studies should be conducted to identify AMF in plant roots in the field. A population genetic approach to studying AMF genetic variability can also be useful for inoculum development. By knowing the amount of genetic variability in an AMF population, the maximum and minimum numbers of spores that will contain a given amount of genetic diversity can be estimated. This could be particularly useful for developing inoculum with high adaptability to different environments.
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The objective of this work was to determine the genetic differences among eight Brazilian populations of the tomato leafminer Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), from the states of Espírito Santo (Santa Tereza), Goiás (Goianápolis), Minas Gerais (Uberlândia and Viçosa), Pernambuco (Camocim de São Félix), Rio de Janeiro (São João da Barra) and São Paulo (Paulínia and Sumaré), using the amplified fragment length polymorphism (AFLP) technique. Fifteen combinations of EcoRI and MseI primers were used to assess divergence among populations. The data were analyzed using unweighted pair-group method, based on arithmetic averages (UPGMA) bootstrap analysis and principal coordinate analysis. Using a multilocus approach, these populations were divided in two groups, based on genetic fingerprints. Populations from Goianápolis, Santa Tereza, and Viçosa formed one group. Populations from Camocim de São Félix, Paulínia, São João da Barra, Sumaré, and Uberlândia fitted in the second group. These results were congruent with differences in susceptibility of this insect to insecticides, previously identified by other authors.
Resumo:
The objective of this work was to evaluate the efficiency of EST‑SSR markers in the assessment of the genetic diversity of rubber tree genotypes (Hevea brasiliensis) and to verify the transferability of these markers for wild species of Hevea. Forty‑five rubber tree accessions from the Instituto Agronômico (Campinas, SP, Brazil) and six wild species were used. Information provided by modified Roger's genetic distance were used to analyze EST‑SSR data. UPGMA clustering divided the samples into two major groups with high genetic differentiation, while the software Structure distributed the 51 clones into eight groups. A parallel could be established between both clustering analyses. The 30 polymorphic EST‑SSRs showed from two to ten alleles and were efficient in amplifying the six wild species. Functional EST‑SSR microsatellites are efficient in evaluating the genetic diversity among rubber tree clones and can be used to translate the genetic differences among cultivars and to fingerprint closely related materials. The accessions from the Instituto Agronômico show high genetic diversity. The EST‑SSR markers, developed from Hevea brasiliensis, show transferability and are able to amplify other species of Hevea.
Resumo:
Genetic variants influence the risk to develop certain diseases or give rise to differences in drug response. Recent progresses in cost-effective, high-throughput genome-wide techniques, such as microarrays measuring Single Nucleotide Polymorphisms (SNPs), have facilitated genotyping of large clinical and population cohorts. Combining the massive genotypic data with measurements of phenotypic traits allows for the determination of genetic differences that explain, at least in part, the phenotypic variations within a population. So far, models combining the most significant variants can only explain a small fraction of the variance, indicating the limitations of current models. In particular, researchers have only begun to address the possibility of interactions between genotypes and the environment. Elucidating the contributions of such interactions is a difficult task because of the large number of genetic as well as possible environmental factors.In this thesis, I worked on several projects within this context. My first and main project was the identification of possible SNP-environment interactions, where the phenotypes were serum lipid levels of patients from the Swiss HIV Cohort Study (SHCS) treated with antiretroviral therapy. Here the genotypes consisted of a limited set of SNPs in candidate genes relevant for lipid transport and metabolism. The environmental variables were the specific combinations of drugs given to each patient over the treatment period. My work explored bioinformatic and statistical approaches to relate patients' lipid responses to these SNPs, drugs and, importantly, their interactions. The goal of this project was to improve our understanding and to explore the possibility of predicting dyslipidemia, a well-known adverse drug reaction of antiretroviral therapy. Specifically, I quantified how much of the variance in lipid profiles could be explained by the host genetic variants, the administered drugs and SNP-drug interactions and assessed the predictive power of these features on lipid responses. Using cross-validation stratified by patients, we could not validate our hypothesis that models that select a subset of SNP-drug interactions in a principled way have better predictive power than the control models using "random" subsets. Nevertheless, all models tested containing SNP and/or drug terms, exhibited significant predictive power (as compared to a random predictor) and explained a sizable proportion of variance, in the patient stratified cross-validation context. Importantly, the model containing stepwise selected SNP terms showed higher capacity to predict triglyceride levels than a model containing randomly selected SNPs. Dyslipidemia is a complex trait for which many factors remain to be discovered, thus missing from the data, and possibly explaining the limitations of our analysis. In particular, the interactions of drugs with SNPs selected from the set of candidate genes likely have small effect sizes which we were unable to detect in a sample of the present size (<800 patients).In the second part of my thesis, I performed genome-wide association studies within the Cohorte Lausannoise (CoLaus). I have been involved in several international projects to identify SNPs that are associated with various traits, such as serum calcium, body mass index, two-hour glucose levels, as well as metabolic syndrome and its components. These phenotypes are all related to major human health issues, such as cardiovascular disease. I applied statistical methods to detect new variants associated with these phenotypes, contributing to the identification of new genetic loci that may lead to new insights into the genetic basis of these traits. This kind of research will lead to a better understanding of the mechanisms underlying these pathologies, a better evaluation of disease risk, the identification of new therapeutic leads and may ultimately lead to the realization of "personalized" medicine.
Resumo:
Les Champignons Endomycorhiziens Arbusculaires (CEA) forment une symbiose racinaire avec environ 80% des espèces connues de plantes vasculaires. Ils occupent une position écologique très importante liée aux bénéfices qu'ils confèrent aux plantes. Des études moléculaires effectuées sur des gènes ribosomaux ont révélé un très grand polymorphisme, tant à l'intérieur des espèces qu'entre celles-ci. Ces champignons étant coenocytiques et multinucléés, l'organisation de cette variabilité génétique intraspécifique pourrait avoir différentes origines. Ce travail se propose d'examiner l'organisation et l'évolution de cette variabilité. Sur la base de fossiles, l'existence des CEA remonte à au moins 450 millions d'années. Cette symbiose peut donc être considérée comme ancienne. Les premières données moléculaires n'indiquant pas de reproduction sexuée, une hypothèse fut élaborée stipulant que les CEA seraient des asexués ancestraux. La première partie de cette thèse (chapitre 2) met en évidence l'existence de recombinaison dans différents CEA mais montre également que celle-ci est insuffisante pour purger les mutations accumulées. La reproduction étant essentiellement asexuée, on peut prédire que les nombreux noyaux ont probablement divergé génétiquement. En collaboration avec M. Hijri nous avons pu vérifier cette hypothèse (chapitre 2). Dans le chapitre 3 j'ai cherché à comprendre si le polymorphisme était également présent dans une population naturelle du CEA Glomus intraradices au niveau intraspécifique, ce qui n'avait encore jamais été examiné. En comparant les empreintes génétiques d'individus obtenus chacun à partir d'une spore mise en culture, j'ai clairement démontré que d'importantes différences génétiques existent entre ceux-ci. Un résultat similaire, portant sur des traits quantitatifs d'individus de la même population, a été trouvé par A. Koch. Les deux études en ensemble montre que le polymorphisme génétique dans cette population est suffisamment grand pour être important au niveau écologique. Dans le chapitre 4, j'ai cherché a examiner le polymorphisme des séquences du gène BiP au sein d'un individu. C'est la première étude qui examine la diversité génétique du génome de CEA avec un autre marqueur que l'ADN ribosomique. J'ai trouvé 31 types de séquences différentes du gène BiP issu d'un isolat de G. intraradices mis en culture à partir d'une seule spore. Cette variation n'était pas restreinte à des zones sélectivement neutres du BiP. Mes résultats montrent qu'il y a un grand nombre de variants non-fonctionnels, proportionnellement au faible nombre de copies attendues par noyau. Ceci va dans le sens d'une partition de l'information génétique entre les noyaux.<br/><br/>Arbuscular mycorrhizal fungi (AMF) are root symbionts with about 80% of all known species of vascular land plants. AMF are ecologically important because of the benefits that they confer to plants. Molecular studies on AMF showed that rDNA sequences were highly variable between species and within species. Because AMF are coenocytic and multinucleate there are several possibilities how this intraspecific genetic variation could be organized. Therefore, the organization and evolution of this variation in AMF were investigated in the present work. Based on fossil records the AMF symbiosis has existed for 450 Million years and is therefore considered ancient. First molecular data indicated no evident sexual reproduction and gave rise to the hypothesis that AMF might be ancient asexuals. The first part of this thesis (Chapter 2) shows evidence for recombination in different AMF but also indicates that it has not been frequent enough to purge accumulated mutations. Given asexual reproduction, it has been predicted that the many nuclei in AMF should diverge leading to genetically different nuclei. This hypothesis has been confirmed by an experiment of M. Hijri and is also included in chapter 2 as the results were published together. In chapter 3 I then investigated whether intraspecific genetic variation also exists in a field population of the AMF Glomus intraradices. Comparing genetic fingerprints of individuals derived from single spores I could clearly show that large genetic differences exist. A similar result, based on quantitative genetic traits, was found for the same population by A. Koch. The two studies taken together show that the genetic variation observed in the population is high enough to be of ecological relevance. Lastly, in chapter 4, I investigated within individual genetic variation among BiP gene sequences. It is the first study that has analyzed genetic diversity in the AMF genome in a region of DNA other than rDNA. I found 31 sequence variants of the BiP gene in one G. intraradices isolate that originated from one spore. Genetic variation was not only restricted to selectively neutral parts of BiP. A high number of predicted non-functional variants compared to a likely low number of copies per nucleus indicated that functional genetic information might even be partitioned among nuclei. The results of this work contribute to our understanding of potential evolutionary strategies of ancient asexuals, they also suggest that genetic differences in a population might be ecologically relevant and they show that this variation even occurs in functional regions of the AMF genome.
Resumo:
Twenty isolates of four fungal species, agents of "Helminthosporium" diseases in cereals, were collected from different regions: nine Bipolarisoryzae isolated from rice (Oryza sativa), seven B.sorokiniana from wheat (Triticum aestivum), two B. maydis, and two Exserohilumturcicum from maize (Zea mays). The strains were compared by PCR-RFLP and RAPD analysis. Size polymorphism among the isolates in the ITS region comprising the 5.8 S rDNA indicated genetic differences among the isolates, while a UPGMA phenogram constructed after the digestion of this region with restriction enzymes showed inter- and intra-specific polymorphism. The RAPD profiles indicated an expressive level of polymorphism among different species, compared with a low level of polymorphism among isolates of the same species. A UPGMA phenogram grouped the isolates according to the species and their host plant. RAPD profiles did not reveal polymorphism that directly correlated climatic factors with geographic source of the isolates of B. sorokiniana, and B. oryzae. Teleomorphic species revealed high similarity with their correspondent anamorphs.
Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology
Resumo:
Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.
Resumo:
Although exceptions may be readily identified, two generalizations concerning genetic differences among species may be drawn from the available allozyme and chromosome data. First, structural gene differences among species vary widely. In many cases, species pairs do not differ more than intraspecific populations. This suggests that either very few or no gene substitutions are required to produce barriers to reproduction (Avise 1976). Second, chromosome form and/or number differs among even closely related species (White 1963; 1978; Fredga 1977; Wright 1970). Many of the observed chromosomal differences involve translocational rearrangements; these produce severe fitness depression in heterozygotes and were, thus, long considered unlikely candidates for the fixation required of genetic changes leading to speciation (Wright 1977). Nonetheless, the fact that species differences are frequently translocational argues convincingly for their fixation despite prejudices to the contrary. Haldane's rule states that in the F of interspecific crosses, the heterogametic sex is absent or sterile in the preponderance of cases (Haldane 1932). This rule definitely applies in the genus Dr°sophila (Ehrman 1962). Sex chromosome translocations do not impose a fitness depression as severe as that imposed by autosomal translocations, and X-Y translocations may account for Haldane's rule (Haldane 1932). Consequently a study of the fit ness parameters of an X·yL and a yS chromosome in Drosophila melanogaster populations was initiated by Tracey (1972). Preliminary results suggested that x.yL//YSmales enjoyed a mating advantage with X·yL//X·yL females, that this advantage was frequency dependent, that the translocation produced sexual isolation and that interactions between the yL, yS and a yellow marker contributed to the observed isolation (Tracey and Espinet 1976; Espinet and Tracey 1976). Encouraged by the results of these prelimimary studies, further experiments were performed to clarify the genetic nature of the observed sexual isolation, S the reality of the y frequency dependent fitness .and the behavioural changes, if any, produced by the translocation. The results of this work are reported herein. Although the marker genes used in earlier studies, sparkling poliert an d yellow have both been found to affect activity,but only yellow effects asymmetric sexual isolation. In addition yellow effects isolation through an interaction with the T(X-y) chromosomes, yS also effects isolation, and translocational strains are isolated from those of normal karyotype in the absence of marker gene differences. When yS chromosomes are in competition with y chromosomes on an X.yL background, yS males are at a distinct advantage only when their frequency is less than 97%. The sex chromosome translocation alters the normal courtship pattern by the incorporation of circling between vibration and licking in the male repertoire. Finally a model of speciation base on the fixation of this sex chromosome translocation in a geographically isolated gene pool is proposed.
Resumo:
A dispersal polymorphism may exist in emigrants from cyclic populations of Microtus '~nnsylvanicus biasing trap-revealed movements of unenclosed animals in favour of sedentary or colonizing individuals. The dispersal tendency of emigrants from an enclosed population was investigated by releasing animals via tubes into one of two adjacent enclosures, one vacant and one inhabited. Individuals from the enclosed population were monitored for age, sex, weight and electrophoretically detectable serum transferrin genotype in an intensive live-trapping program. In 1973 the minimum number alive in the introduced enclosed study population reached approximately l67/ha when breeding stopped in October. In 1974 intensive breeding increased the population density to 333/ha by mid-July when a long decline in numbers and breeding intensity began without an intervening plateau. An adjacent unenclosed area had a much lower density and longer breeding season in 1974. The growth rate of young males in the enclosed population tended to be lowest during the decline period in 1974. Survival of the enclosed population was high throughout but was lowest during the decline phase in both sexes, especially males. Low transferrin heterozygote survival during the decline coincided with a significant heterozygote deficiency in females whereas in males genotype frequencies did not depart from Hardy-Weinberg equilibrium values throughout th.e study. Twenty-nine suitable ani.mals were released during the decline in five periods from July to November 1974. The proportions of males and transferrin heterozygotes in the released graun were generally greater than in the source population~ In the test enclosures 21% of the released animals continued their movement through the vacant area while 41% (no significant difference) moved through the inhabited enclosure. In the vacant test area, females had a greater tendency than males to continue dispersal whereas no difference was noted in the inhabited area. Low frequency of captures in the tubes, predator disturbances and cold weather forced the termination of the study. The role of dispersal as a population regulating mechanism was further substantiated. The genetic differences between emigrant and resident animals lend support to Howard's hypothesis that a genetic polymorphism influences the tendency to disperse. Support is also given to Myers' and Krebs' contention that among dispersers an additional density dependent polymorphism influences the distance dispersed.