Genetic Variation In Response Research Articles

Genetic differ in TLR4 gene polymorphisms and expression involved in Salmonella natural and artificial infection respectively in Chinese native chicken breeds

Salmonella enteritidis (SE) is a foodborne pathogen that negatively affects both animal and human health. Genetic variations in response to pathogenic SE colonization or to SE vaccination were measured in chicken resource populations. Toll-like receptor 4 (TLR4) is part of a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens and in the innate defense against infection. In this study, TLR4 was investigated the association of TLR4 gene polymorphisms with Salmonella natural infection situation of birds from two distinct Chinese genetic breeds. One SNP G1894C in the second intron of chicken TLR4 (chTLR4) was scanned in the two hens breed, which showed significant association with Salmonella natural infection situation (P<0.05). Genetic variations in response to pathogenic SE colonization also existed in distinct Chinese chicken resource population. In this study, mRNA expression of TLR4 was detected to investigate the association with the effect of artificial SE challenge in heterophil granulocytes and spleen of chicks from two distinct Chinese genetic breeds at 1, 3 and 10 day post-infection during the acute infection period. It clearly showed that young chicks' response to SE infection was regulated by TLR4 mRNA expression. The results suggest that genetics, time, gender, and interactions among these factors, play important roles in TLR4 mRNA basic values and copies modulation of SE mediated immune response in distinct Chinese chickens.

Potential for adaptation in response to thermal stress in an intertidal macroalga.

Understanding responses of marine algae to changing ocean temperatures requires knowledge of the impacts of elevated temperatures and the likelihood of adaptation to thermal stress. The potential for rapid evolution of thermal tolerance is dependent on the levels of heritable genetic variation in response to thermal stress within a population. Here, we use a quantitative genetic breeding design to establish whether there is a heritable variation in thermal sensitivity in two populations of a habitat-forming intertidal macroalga, Hormosira banksii (Turner) Descaisne. Gametes from multiple parents were mixed and growth and photosynthetic performance were measured in the resulting embryos, which were incubated under control and elevated temperature (20°C and 28°C). Embryo growth was reduced at 28°C, but significant interactions between male genotype and temperature in one population indicated the presence of genetic variation in thermal sensitivity. Selection for more tolerant genotypes thus has the ability to result in the evolution of increased thermal tolerance. Furthermore, genetic correlations between embryos grown in the two temperatures were positive, indicating that those genotypes that performed well in elevated temperature also performed well in control temperature. Chlorophyll a fluorescence measurements showed a marked decrease in maximum quantum yield of photosystem II (PSII) under elevated temperature. There was an increase in the proportion of energy directed to photoinhibition (nonregulated nonphotochemical quenching) and a concomitant decrease in energy used to drive photochemistry and xanthophyll cycling (regulated nonphotochemical quenching). However, PSII performance between genotypes was similar, suggesting that thermal sensitivity is related to processes other than photosynthesis.

Genetic variation in responses to dietary restriction — An unbiased tool for hypothesis testing

Dietary restriction (DR) extends lifespan in a wide range of animal models. A major obstacle to understanding how DR modulates lifespan and aging-related dysfunction is the multiplicity of physiological and molecular changes associated with DR. Unraveling their importance to the longevity effect of DR remains a major challenge. In this perspective, we review the marked genetic variation in the response to DR of multiple recombinant inbred (RI) mouse strains. We illustrate how this genetic variation can be exploited to probe the mechanisms mediating lifespan extension by DR, as well as uncover its limits as an intervention. RI strains exhibit marked variation in their lifespan as well as physiological responses to DR. Quantitative genetic and statistical tools can use this phenotypic variation to probe the importance of physiological and molecular changes that have been hypothesized to play roles in DR-mediated lifespan extension.

Health effects of low-carbohydrate diets: where should new research go?

There has been considerable debate about the metabolic effects of restricting carbohydrate intake in weight and diabetes management. However, the American Diabetes Association has noted that weight and metabolic improvements can be achieved with low carbohydrate, low fat (implicitly higher carbohydrate), or a Mediterranean style diet (usually an intermediate level of carbohydrate). Our paper addresses variability in the definition for low or restricted carbohydrate, the effects of carbohydrate restriction on diabetes-related health outcomes, strategies for restricting carbohydrate intake, and potential genetic variability in response to dietary carbohydrate restriction. Issues for future research are also addressed.

De novo assembly of the transcriptome of an invasive snail and its multiple ecological applications

Studying how invasive species respond to environmental stress at the molecular level can help us assess their impact and predict their range expansion. Development of markers of genetic polymorphism can help us reconstruct their invasive route. However, to conduct such studies requires the presence of substantial amount of genomic resources. This study aimed to generate and characterize genomic resources using high throughput transcriptome sequencing for Pomacea canaliculata, a nonmodel gastropod indigenous to Argentina that has invaded Asia, Hawaii and southern United States. De novo assembly of the transcriptome resulted in 128,436 unigenes with an average length of 419 bp (range: 150-8556 bp). Many of the unigenes (2439) contained transposable elements, showing the existence of a source of genetic variability in response to stressful conditions. A total of 3196 microsatellites were detected in the transcriptome; among 20 of the randomly tested microsatellites, 10 were validated to exhibit polymorphism. A total of 15,412 single-nucleotide polymorphisms (SNPs) were detected in the ORFs. LC-MS/MS analysis of the proteome of juveniles revealed 878 proteins, of which many are stress related. This study has demonstrated the great potential of high throughput DNA sequencing for rapid development of genomic resources for a nonmodel organism. Such resources can facilitate various molecular ecological studies, such as stress physiology and range expansion.

Identification of quantitative trait loci for ion homeostasis and salt tolerance in barley (Hordeum vulgare L.)

Ion homeostasis is considered to be one of the most important mechanisms underlying salt stress tolerance. We used the Steptoe × Morex barley doubled haploid population to screen for genetic variation in response to salinity stress at an early development stage in a hydroponics system, focusing on ion homeostasis. Salinity induced a strong adverse effect on growth of the parents and their derived population, with Steptoe as the more tolerant parent. Steptoe maintained higher concentrations of K+, Na+ and Cl− in the roots and a similar shoot/root ion ratio (<1) under stress conditions compared to control conditions. In contrast, Morex had higher concentrations of these ions in the shoots under stress and a doubled shoot/root ion ratio relative to control conditions, indicating that salt exclusion might contribute to the higher tolerance of Steptoe. Correlation and path analysis demonstrated that shoot Cl− contents most strongly affected salt tolerance and suggest that both Na+ and Cl− contents are important for salinity stress tolerance in barley. We identified 11 chromosomal regions involved in the control of the variation observed for salt tolerance and various salt stress response traits, including Na+, Cl− and K+ contents in shoots. Two specific regions on chromosomes 2H and 3H were found controlling ion contents and salt tolerance, pointing to genes involved in ion homeostasis that contribute to salt tolerance.

Agronomic performance of wheat cultivars in response to nitrogen fertilization levels

The release of wheat cultivars with different nutritional demands and yield potential hinders generalized recommendations for nitrogen fertilization. This study was designed to evaluate the effects of different nitrogen fertilization levels (0, 60, 120 and 180 kg ha-1 of N) on the agronomic performance of six wheat cultivars (Triticum aestivum L.) in two harvests. A randomized block factorial design with three replications was used. The response to fertilization levels was evaluated through AMMI (Additive Main effects and Multiplicative Interaction) and GGE (Genotype main effects and Genotype x Environment interaction) biplot graphic methodologies and polynomial regression. There was genetic variability in response to nitrogen fertilization in the cultivars studied. The biggest increases in yield were observed under a more suitable water regime. The higher performance of yield components was associated with higher nitrogen fertilization levels.

Meta‐Analysis of Susceptibility of Woody Plants to Loss of Genetic Diversity through Habitat Fragmentation

Shrubs and trees are assumed less likely to lose genetic variation in response to habitat fragmentation because they have certain life-history characteristics such as long lifespans and extensive pollen flow. To test this assumption, we conducted a meta-analysis with data on 97 woody plant species derived from 98 studies of habitat fragmentation. We measured the weighted response of four different measures of population-level genetic diversity to habitat fragmentation with Hedge's d and Spearman rank correlation. We tested whether the genetic response to habitat fragmentation was mediated by life-history traits (longevity, pollination mode, and seed dispersal vector) and study characteristics (genetic marker and plant material used). For both tests of effect size habitat fragmentation was associated with a substantial decrease in expected heterozygosity, number of alleles, and percentage of polymorphic loci, whereas the population inbreeding coefficient was not associated with these measures. The largest proportion of variation among effect sizes was explained by pollination mechanism and by the age of the tissue (progeny or adult) that was genotyped. Our primary finding was that wind-pollinated trees and shrubs appeared to be as likely to lose genetic variation as insect-pollinated species, indicating that severe habitat fragmentation may lead to pollen limitation and limited gene flow. In comparison with results of previous meta-analyses on mainly herbaceous species, we found trees and shrubs were as likely to have negative genetic responses to habitat fragmentation as herbaceous species. We also found that the genetic variation in offspring was generally less than that of adult trees, which is evidence of a genetic extinction debt and probably reflects the genetic diversity of the historical, less-fragmented landscape.

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross

The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.

Overview of Symposium “Systems Genetics in Nutrition and Obesity Research”1,2

Systems genetics is a novel approach for identifying the complex genetic architecture of quantitative traits and gene-environment interactions via detection of connections from genetic variation through intermediate phenotypes to overlying systems level phenotypes. This symposium, conducted at the Experimental Biology 2010 conference, aimed at educating nutrition researchers about the use of systems genetics as a tool for linking genetic variation to nutrient metabolism and energy balance and their overlying effects on health and disease. Basic concepts of systems genetics and the analytical framework used in these studies were presented. Further, the utility of genetic reference populations for gene-environment interaction studies along with specific studies addressing genetic variation in responsiveness to nutrients were discussed.

Is there genetic variation in the response to competition intensity in juvenile brown troutSalmo trutta?

Effects of intraspecific competition intensities on the relative performance (growth and movement) of juvenile brown trout Salmo trutta originating from nine different families were tested in tank experiments and in semi-natural streams. Both growth and movement differed consistently among families, indicating genetic variation in these traits. There were no significant interaction effects, however, between the intensity of competition and family origin on performance in either of the two experimental systems. Thus, genetic variation in response to competition intensity appeared to be limited in the population from which the juveniles used in this experiment originate.

Platelet function variability and non-genetic causes

Dual antiplatelet therapy (DAPT) has been established for the treatment of coronary artery disease, especially in and after acute coronary syndromes, and after coronary interventions. Data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and intrinsic mechanisms. The clinical consequence of clopidogrel non-responsiveness is severe cardiovascular complications. Besides genetic variability in response to antiplatelet therapy, non-genetic causes such as drug interactions (proton-pump inhibitors, statins, calcium-channel blockers, coumarin derivates, antibiotics, antimycotics) and co-morbidities (diabetes mellitus, renal failure, obesity) are responsible for this phenomenon. Large clinical trials with standardised laboratory methods and hard clinical endpoints are needed to identify these interactions with clopidogrel and predictors for its non-responsiveness.

Genetic variability in response to clopidogrel therapy and its clinical implications

This article concentrates on individual genetic differences responsible for variations of action of clopidogrel, which have been found to be partially responsible for increased cardiovascular events in patients with coronary artery disease under dual antiplatelet therapy. According to these results, genotyping for the relevant gene polymorphisms, especially for the CYP2C19 loss-of-function alleles, has been discussed to be an effective method of individualising and optimising clopidogrel treatment. However, due to the facts that 1) there are no prospective studies demonstrating a clinical benefit of personalising antiplatelet therapy based on genotyping; 2) CYP2C19 polymorphisms account for only approximately 12% of variability in clopidogrel platelet response; 3) the positive predictive value of CYP2C19 loss-of-function polymorphisms for cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention is only approximately 12% - 20%; 4) it is likely that other clinical factors and risk constellations might be of greater clinical importance; and 5) it is unknown whether a specific genetic polymorphism is capable of influencing outcome for the individual patient; genetic profiling cannot be recommended for routine use at present but will remain of considerable scientific interest.

Improved lentil production by utilizing genetic variability in response to phosphorus fertilization

A field experiment was undertaken for evaluating the performance of three lentil genotypes with phosphorus (P) fertilization at four rates: 0, 40, 60, and 80 kg P2O5 ha−1 under rain-fed conditions. Genotypes of lentil were: Masoor-93, Markaz-2001, and NARC-02/2. Masoor-93 showed the highest seed yield, crop-growth rate, net assimilation rate, and seed protein contents among all the tested cultivars. P applied at the highest rate (80 kg ha−1) caused the best positive response with respect to physiological traits, growth attributes, and yield components. Furthermore, the application of P-fertilizer was found to be feasible in economic terms, as the net return, value-to-cost ratio, and relative increase in income were enhanced successively at higher phosphorus rates. It was concluded that for maximum potential yield of lentil, genotype Masoor-93 is the best suited under rain-fed conditions provided that its P nutrition is enhanced. The pronounced genetic variability in lentil-yield traits suggests that nutrient-efficient germplasm can be screened through breeding programmes to promote lentil production.

Frequency ofBtResistance Alleles inHelicoverpa armigerain the Xinjiang Cotton-Planting Region of China

Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a key insect pest of cotton in Xinjiang cotton-planting region of northwest China. In this region, cotton is grown on average ≈ 1.65 million ha (1.53 ≈ 1.80 million ha) annually in largely monoculture agricultural landscapes, similarly to cropping systems in the United States or Australia. Under such cropping regimes, naturally occurring refuges (with non-Bt crops) may be insufficient to prevent H. armigera resistance development to Bt toxins. Therefore, we assessed frequency of alleles conferring resistance to Cry1Ac toxin of F(1) and F(2) offspring of H. armigera isofemale lines from two distinct localities in the region during 2005-2009. More specifically, a total of 224 isofemale lines was collected from Korla County (≈ 70% Bt cotton adoption) and 402 lines from Shache County (≈ 5% Bt cotton planting). Subsequent offspring was screened on Cry1Ac artificial diet. From 2005 to 2009, resistance gene frequency in Korla fluctuated between 0.0000 and 0.0040, while being 0.0000-0.0008 in individuals collected from Shache, and there were no significant increases in both counties from 2005 to 2009. Relative average development rates (RADRs) of larvae in F(1) tests showed significant increases from Korla, but not in Shache. RADR of F(1) larvae is significantly correlated with RADR of F(2) offspring, indicating genetic variation in response to toxin in field H. armigera population. Although the occurrence of Cry1Ac resistance alleles was low in Xinjiang cotton-planting region of China, particular attention should be given to H. armigera resistance development in Korla County.

Genetic variation in responses to different soil water treatments in Quercus robur L.

The effect of soil water content on growth and growth cessation was studied in 18 provenances from northern Europe and 20 Danish open-pollinated families of Quercus robur in a greenhouse experiment. The objective was to study the genotypic responses, phenotypic plasticity and genotype by environment interactions, with regards to growth and to different levels of soil water content. The aim was to increase the knowledge on the genetic and adaptive potential of Q. robur to grow under different water stress conditions. Knowledge on genetic and adaptive potential can be used for practical seed zone management. Differences in growth between provenances were strongly related to latitude. Provenances of southernmost origin reacted vigorously to irrigation compared with Scandinavian provenances. For growth, the rank of provenances was the same at high and medium soil water treatments. Increased growth correlated with a higher number of secondary shoots and a prolonged growing season. Low soil water content initiated early growth cessation in all provenances. Root biomass was affected by soil water treatment and the highest root biomass was observed with medium and high soil water treatments. The results demonstrated a large evolutionary potential in relation to water treatment. The southernmost genotypes responded more strongly in growth to increased soil water level, but the local material showed a large variation and was less prone to early frost damage. The growth of Danish provenances of Q. robur was not reduced with high soil water treatment, in contrast to a study using Danish Fagus sylvatica provenances, indicating that Q. robur is well adapted to high soil water conditions.

Genetic variability in response to clopidogrel therapy: clinical implications

This editorial refers to ‘CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case–control study’[†][1], by A.M. Harmsze et al ., on page 3046 In the past few years, it has been realized that cardiovascular events under dual antiplatelet therapy (DAPT) might be associated with a poor response to clopidogrel.1 Based on different platelet function assays, ∼20–25% of clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI) and coronary stenting have been defined as poor responders and were prone to an increased risk of recurrent cardiovascular events.2 Reasons for a diminished action of clopidogrel are multifactorial and include besides non-compliance, under-dosing, drug–drug interactions, and several co-morbidities (e.g. diabetes mellitus, hyperlipidaemia), also genetic disorders that interact with intestinal absorption, metabolic activation in the liver, and pharmacodynamics.3 In the current issue of the journal Harmsze and co-workers4 have elegantly demonstrated in the so far biggest patient cohort with stent thrombosis ( n = 176) during DAPT after PCI and stent implantation that carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk of stent thrombosis, while no effect of other investigated genetic variants for genes involved in clopidogrel absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C19*3, CYP2C9*2, CYP3A4*1B, and CYP3A5*3), or the P2Y1 receptor (P2Y1A1622G) was seen. Clopidogrel is an ADP receptor inhibitor prodrug. After intestinal absorption (ABCB1 gene), the majority (85%) of the … [1]: #fn-1

Genetic mapping of natural variation in a shade avoidance response: ELF3 is the candidate gene for a QTL in hypocotyl growth regulation

When plants become shaded by neighbouring plants, they perceive a decrease in the red/far-red (R/FR) ratio of the light environment, which provides an early and unambiguous warning of the presence of competing vegetation. The mechanistic bases of the natural genetic variation in response to shade signals remain largely unknown. This study demonstrates that a wide range of genetic variation for hypocotyl elongation in response to an FR pulse at the end of day (EOD), a light signal that simulates natural shade, exists between Arabidopsis accessions. A quantitative trait locus (QTL) mapping analysis was done in the Bayreuth×Shahdara recombinant inbred line population. EODINDEX1 is the most significant QTL identified in response to EOD. The Shahdara alleles at EODINDEX1 caused a reduced response to shade as a consequence of an impaired hypocotyl inhibition under white light, and an accelerated leaf movement rhythm, which correlated positively with the pattern of circadian expression of clock genes such as PRR7 and PRR9. Genetic and quantitative complementation analyses demonstrated that ELF3 is the most likely candidate gene underlying natural variation at EODINDEX1. In conclusion, ELF3 is proposed as a component of the shade avoidance signalling pathway responsible for the phenotypic differences between Arabidopsis populations in relation to adaptation in a changing light environment.

Hidden variation mapped

Many biological systems are insensitive to a certain degree of environmental variation. Because such systems present some buffering properties (for example, crosstalk between pathways, redundancies and feedback loops), phenotypic variation may occur within the developing system yet be buffered at the level of its output. This buffering allows the accumulation of mutations affecting the system, for example, the activity of signaling pathways, without affecting its end product. Such cryptic genetic variation may have an important function in phenotypic evolution (Wagner, 2005). For instance, it has been proposed that the epidemic aspect of several complex genetic diseases in modern human societies could be explained by the uncovering of cryptic genetic variation in response to the abrupt change of lifestyle in recent generations (Gibson, 2009). Consequently, it is of key interest to study the genetic architecture and molecular nature of cryptic variation that segregates in natural populations. The extent of such cryptic genetic variation has so far been underestimated because of the difficulty in detecting it. In this issue, cryptic genetic variation affecting somatic sex determination mechanisms is revealed among wild isolates of the nematode Caenorhabditis elegans (Chandler, 2010). Using a quantitative genetic approach, the author detected several genomic regions underlying this variation. This work opens interesting perspectives for understanding the evolution of sex determination at the intraspecific level and highlights the importance of considering cryptic variation when studying an apparently invariant system.

ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA “Boxed Warning”

The recent US Food and Drug Administration (FDA) “boxed warning” on clopidogrel raises important questions for practitioners and patients. The warning addresses the need for pharmacogenomic testing to identify patients’ altered clopidogrel metabolism and thus their risk for a suboptimal clinical response to clopidogrel. Although there is an expanding database on genetic polymorphisms that may affect clopidogrel metabolism and thus clinical outcomes, there are no evidence-based data upon which todevelop specific recommendations on the role of genetic testing in routine care nor strategies proven to improve the safety/efficacy of specific pharmacologic approaches. To provide guidance on this issue, the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) convened a writing committee. The ACCF and AHA adhere to a rigorous policy regarding relationships with industry and other entities (RWI) of authors and peer reviewers for clinical document development (see http://www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards/Relationships-With-Industry-Policy.aspx). This policy requires that a majority of writing committee members have no relevant relationships with industry to this topic, a standard that has been achieved for this document as indicated in Appendix 1. In the spirit of full disclosure, comprehensive RWI (RWI not relevant to this document) for all authors is available online for public view. RWI …