Analysis of the Genotype Interaction of Four-Year-Old Populus euramericana Using the BLUP-GGE Technique

Poplar is a commercially globalized tree species that provides energy and economic and ecological support. To evaluate the twelve hybrid Populus euramericana genotypes developed in China, a total of six locations were selected for the current study, comprising four climatic types and three kinds of soil. The objective of this study was to characterize the early stages of Populus euramericana growth and to test the locations; to identify good genotypes for stable and high yield; and to offer practical experience and technical assistance for further breeding of Populus euramericana. The main research methods included the statistical description of tree heights and diameter at breast height (DBH), the establishment of a mixed effect model to analyze the genotype and environmental interaction effect (G × E), the use of best linear unbiased prediction (BLUP) values as GGE biplots to achieve visual screening, and the calculation of genetic parameters. Results show that the genotype effect (G), the environmental effect (E), and the G × E interaction is significant; the BLUP value has a strong correspondence with the observed value; the goodness of fit of all biplots can explain more than 85% of the variation; the broad-sense heritability of tree height and DBH is 0.13 and 0.3, respectively; and the type-B correlation is 0.36 and 0.65. In addition, G5, G7, G4, and G9 are excellent genotypes with high yield and stability; using the tree height and DBH of these four genotypes can achieve genetic gains of 3.35% and 0.81%. The conclusions of this study are as follows: the rank-change and scale-effect interactions were distinct; G, E, and G × E all had a significant effect on the growth of poplar trees during their early stage; G4, G5, G7, and G9 genotypes have favorable development characteristics; and N146 is an excellent source of paternal genetics.

Plasticity across levels: relating epigenomic, transcriptomic, and phenotypic responses to osmotic stress in a halotolerant microalga

Phenotypic plasticity, the ability of a given genotype to produce alternative phenotypes in response to its environment of development, is an important mechanism for coping with variable environments. While the mechanisms underlying phenotypic plasticity are diverse, their relative contributions need to be investigated quantitatively to better understand the evolvability of plasticity across biological levels. This requires relating plastic responses of the epigenome, transcriptome, and organismal phenotype, and how they vary with the genotype. Here we carried out this approach for responses to osmotic stress in Dunaliella salina, a green microalga that is a model organism for salinity tolerance. We compared two strains that show markedly different demographic responses to osmotic stress, and showed that these phenotypic responses involve strain- and environment-specific variation in gene expression levels, but a relative low - but significant - effect of strain x environment interaction. We also found an important genotype effect on the genome-wide methylation pattern, but little contribution from environmental conditions to the latter. However, we did detect a significant marginal effect of epigenetic variation on gene expression, beyond the influence of genetic differences on epigenetic state, and we showed that hypomethylated regions are correlated with higher gene expression. Our results indicate that epigenetic mechanisms are either not involved in the rapid plastic response to environmental change in this species, or involve only few changes in trans that are sufficient to trigger concerted changes in the expression of many genes, and phenotypic responses by multiple traits.

Analysis of Genotype-Interaction of a 4-Year-Old Populus euramericana Using BLUP-GGE Technique

Poplar is a globalized commercial tree species that supports humanity's economy, energy, and ecology. To evaluate the twelve hybrid Populus euramericana genotypes developed in China, a total of six locations were selected for the test, comprising four climatic types and three soil kinds. The objective of this study is to characterize the early stages of Populus euramericana growth and test locations; to identify good genotypes for stable and high yield that may be encouraged; and to offer practical experience and technical assistance for further breeding of Populus euramericana. Main research methods include the statistical description of tree heights and diameter at breast heights[DBH], the establishment of a mixed effect model to analyze the genotype and environmental interaction effect [G×E], the use of best linear unbiased prediction[BLUP] values as GGE biplots to achieve visual screening, and the calculation of genetic parameters. Results show that the genotype effect [G], the environmental effect [E], and the G×E is significant; the BLUP value has a strong correspondence with the observed value; the goodness of fit of all biplots can explain more than 85% of the variation; broad-sense heritability of tree height and DBH is 0.13 and 0.3, type-B correlation is 0.36 and 0.65; G5, G7, G4 and G9 are excellent genotypes with high yield and stability; using these four genotypes tree height and DBH can get 3.35% and 0.81% genetic gains.The study concludes as follows: Rank-change interaction and scale-effect interaction were distinctly occurred. The G, E, and G×E all had a significant effect on the growth of poplar trees during their early stage. G4, G5, G7, and G9 genotypes have favorable development characteristics. N146 is a great source of paternal genetics.

The Role of the Serotonin Transporter as a Genetic Risk Factor in the Development of Drug Addiction

<p>Drug addiction is a ubiquitous phenomenon worldwide that places tremendous financial and psychological burden on societies, families and the individual. Interestingly, only a small percentage of individuals ( 20%), regardless their drug of choice, go on to develop the compulsive behaviours that define drug addiction. Clinical studies have shown that there is a subset of the population with a genetically determined reduction in the serotonin transporter that may increase vulnerability to developing a variety of psychiatric disorders like depression, anxiety and drug addiction. To investigate the influence of reduced serotonin transporter function in the laboratory we studied the effects of MDMA (‘ecstasy’) and heroin in a genetically altered animal model: the serotonin transporter (SERT) knockout rat. Homozygous (HOM) animals lack SERT function completely while heterozygous (HET) have about 50% SERT function compared to the wild type (WT). Groups of HOM, HET and WT animals completed MDMA or heroin self-administration experiments. A robust genotype effect emerged for animals self-administering MDMA; facilitation of MDMA self-administration was inversely related to SERT function. HOM animals, without exception, reached acquisition criterion significantly faster than the HET animals; HET animals then showed higher acquisition rates compared to the WT animals. In contrast, there were no differences between the genotypes when animals self-administered heroin. To investigate the driving force behind facilitated MDMA self-administration in animals with reduced SERT function locomotor activity and conditioned taste aversion experiments were undertaken. In contrast to the drug self-administration experiments,MDMA induced hyperactivity was positively related to SERT function. Thus, it was significantly reduced in HOM and HET animals compared to the WT. Again, heroin treatment did not produce differences in locomotion between the genotypes. MDMA induced conditioned taste aversion revealed only a main effect of dose with robust conditioned taste aversion for both drug doses, although a trend indicated that HOM animals may have heightened sensitivity to MDMA. However, heroin treatment failed to produce a conditioned taste aversion effect in any of the groups regardless of dose. Beyond the aforementioned behavioural experiments striatal brain tissue from the animals that had previously self-administered MDMA or heroin was analysed via quantitative reverse transcription polymerase chain reaction; five targets were evaluated to quantify drug induced changes in brain derived neurotrophic factor gene expression (BDNF). Several BDNF isoforms (total BDNF, BDNF III and BDNF IV) were significantly increased in animals that had self-administered MDMA; this effect was true across HOM, HET and WT subjects. Comparatively, animals that had self-administered heroin did not show a difference in BDNF expression compared to untreated control animals. This suite of experiments provides insight into the influence of a compromised serotonergic system on the development of drug addiction. That is, while reduced SERT function does not appear to augment the addictive properties of drugs like heroin there is reason to suspect that it does confer additional susceptibility to developing addiction to drugs like MDMA, highlighting the hypothesis that different classes of addictive substances act through different neurobiological pathways.</p>

The Role of the Serotonin Transporter as a Genetic Risk Factor in the Development of Drug Addiction

<p>Drug addiction is a ubiquitous phenomenon worldwide that places tremendous financial and psychological burden on societies, families and the individual. Interestingly, only a small percentage of individuals ( 20%), regardless their drug of choice, go on to develop the compulsive behaviours that define drug addiction. Clinical studies have shown that there is a subset of the population with a genetically determined reduction in the serotonin transporter that may increase vulnerability to developing a variety of psychiatric disorders like depression, anxiety and drug addiction. To investigate the influence of reduced serotonin transporter function in the laboratory we studied the effects of MDMA (‘ecstasy’) and heroin in a genetically altered animal model: the serotonin transporter (SERT) knockout rat. Homozygous (HOM) animals lack SERT function completely while heterozygous (HET) have about 50% SERT function compared to the wild type (WT). Groups of HOM, HET and WT animals completed MDMA or heroin self-administration experiments. A robust genotype effect emerged for animals self-administering MDMA; facilitation of MDMA self-administration was inversely related to SERT function. HOM animals, without exception, reached acquisition criterion significantly faster than the HET animals; HET animals then showed higher acquisition rates compared to the WT animals. In contrast, there were no differences between the genotypes when animals self-administered heroin. To investigate the driving force behind facilitated MDMA self-administration in animals with reduced SERT function locomotor activity and conditioned taste aversion experiments were undertaken. In contrast to the drug self-administration experiments,MDMA induced hyperactivity was positively related to SERT function. Thus, it was significantly reduced in HOM and HET animals compared to the WT. Again, heroin treatment did not produce differences in locomotion between the genotypes. MDMA induced conditioned taste aversion revealed only a main effect of dose with robust conditioned taste aversion for both drug doses, although a trend indicated that HOM animals may have heightened sensitivity to MDMA. However, heroin treatment failed to produce a conditioned taste aversion effect in any of the groups regardless of dose. Beyond the aforementioned behavioural experiments striatal brain tissue from the animals that had previously self-administered MDMA or heroin was analysed via quantitative reverse transcription polymerase chain reaction; five targets were evaluated to quantify drug induced changes in brain derived neurotrophic factor gene expression (BDNF). Several BDNF isoforms (total BDNF, BDNF III and BDNF IV) were significantly increased in animals that had self-administered MDMA; this effect was true across HOM, HET and WT subjects. Comparatively, animals that had self-administered heroin did not show a difference in BDNF expression compared to untreated control animals. This suite of experiments provides insight into the influence of a compromised serotonergic system on the development of drug addiction. That is, while reduced SERT function does not appear to augment the addictive properties of drugs like heroin there is reason to suspect that it does confer additional susceptibility to developing addiction to drugs like MDMA, highlighting the hypothesis that different classes of addictive substances act through different neurobiological pathways.</p>

Neurogenic Plasticity in a Serotonin Transporter Knockout Model: Effects of Maternal and Offspring Genotype

<p>Major depressive disorder (MDD) is debilitating mental disorder that is increasing in prevalence. Many theories have tried to explain the aetiology of depression including the classic monoamine deficiency hypothesis and the newer neurogenic hypothesis. The finding that selective serotonin transporter inhibitors (SSRIs) work by increasing extracellular serotonin levels in the brain and have antidepressant effects has formed the basis of the most widely accepted theory of depression, the monoamine hypothesis. However, a genetic reduction in human and animal serotonin reuptake transporters, which also increases extracellular serotonin, is associated with depressive symptomology. This paradox is not explained by the monoamine hypothesis. The key difference between these two scenarios is that genetically induced increases in serotonin occur from development onward, while SSRIs increase serotonin only in adulthood. Furthermore, SSRIs typically take several weeks to confer a therapeutic effect. This finding has led to the hypothesis that, rather than acute monoamine-increasing effects, it is the downstream effects of such increases on neurogenesis and neural plasticity which confer antidepressant effects. To further elucidate the neurobiology of depression, this study sought to examine the effects of genetically increasing serotonin on early postnatal neurogenesis in a serotonin knockout rat model using BrdU immunohistochemistry. We examined both the offspring and maternal genotype effects. We found that SERT-/- offspring had the highest levels of neurogenesis compared with SERT+/- and SERT+/+ at postnatal day 7. In addition we found a maternal genotype effect with SERT+/+ offspring born and reared by SERT+/- mothers having lower neurogenesis compared to SERT+/+ offspring from SERT+/+ mothers. The potential effects of maternal caregiving, neuroplasticity in altered mood and stress responses and the role of 5-HT receptors are discussed.</p>

Neurogenic Plasticity in a Serotonin Transporter Knockout Model: Effects of Maternal and Offspring Genotype

<p>Major depressive disorder (MDD) is debilitating mental disorder that is increasing in prevalence. Many theories have tried to explain the aetiology of depression including the classic monoamine deficiency hypothesis and the newer neurogenic hypothesis. The finding that selective serotonin transporter inhibitors (SSRIs) work by increasing extracellular serotonin levels in the brain and have antidepressant effects has formed the basis of the most widely accepted theory of depression, the monoamine hypothesis. However, a genetic reduction in human and animal serotonin reuptake transporters, which also increases extracellular serotonin, is associated with depressive symptomology. This paradox is not explained by the monoamine hypothesis. The key difference between these two scenarios is that genetically induced increases in serotonin occur from development onward, while SSRIs increase serotonin only in adulthood. Furthermore, SSRIs typically take several weeks to confer a therapeutic effect. This finding has led to the hypothesis that, rather than acute monoamine-increasing effects, it is the downstream effects of such increases on neurogenesis and neural plasticity which confer antidepressant effects. To further elucidate the neurobiology of depression, this study sought to examine the effects of genetically increasing serotonin on early postnatal neurogenesis in a serotonin knockout rat model using BrdU immunohistochemistry. We examined both the offspring and maternal genotype effects. We found that SERT-/- offspring had the highest levels of neurogenesis compared with SERT+/- and SERT+/+ at postnatal day 7. In addition we found a maternal genotype effect with SERT+/+ offspring born and reared by SERT+/- mothers having lower neurogenesis compared to SERT+/+ offspring from SERT+/+ mothers. The potential effects of maternal caregiving, neuroplasticity in altered mood and stress responses and the role of 5-HT receptors are discussed.</p>

Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: long-term outcomes in women and men

Objective: To estimate the effect of the SLCO1B1*5 genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. Methods and Analysis: 69,185 European-ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40 to 79 years at first prescription; treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5mmol/L) at baseline, plus treatment discontinuation. Results: 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol, vs. 41.7% of those with functioning SLCO1B1 (Odds Ratio 1.31: 95% Confidence Intervals 1.1 to 1.55, p=0.001). Fewer males had high cholesterol, and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (Hazard Ratio 1.19: 95%CI 1.03 to 1.37, p=0.01), amounting to five discontinuations per 100 statin-years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3: 95%CI 1.08 to 1.56; p=0.006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. Conclusions: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype-guided statin selection.

A Multi-Marker Test for Analyzing Paired Genetic Data in Transplantation

Emerging evidence suggests that donor/recipient matching in non-HLA (human leukocyte antigen) regions of the genome may impact transplant outcomes and recognizing these matching effects may increase the power of transplant genetics studies. Most available matching scores account for either single-nucleotide polymorphism (SNP) matching only or sum these SNP matching scores across multiple gene-coding regions, which makes it challenging to interpret the association findings. We propose a multi-marker Joint Score Test (JST) to jointly test for association between recipient genotype SNP effects and a gene-based matching score with transplant outcomes. This method utilizes Eigen decomposition as a dimension reduction technique to potentially increase statistical power by decreasing the degrees of freedom for the test. In addition, JST allows for the matching effect and the recipient genotype effect to follow different biological mechanisms, which is not the case for other multi-marker methods. Extensive simulation studies show that JST is competitive when compared with existing methods, such as the sequence kernel association test (SKAT), especially under scenarios where associated SNPs are in low linkage disequilibrium with non-associated SNPs or in gene regions containing a large number of SNPs. Applying the method to paired donor/recipient genetic data from kidney transplant studies yields various gene regions that are potentially associated with incidence of acute rejection after transplant.

Abscisic acid induces somatic embryogenesis and enables the capture of high-value genotypes in Douglas fir (Pseudotsuga menziesii [MIRB.] Franco)

Douglas fir (Pseudotsuga menziesii) is one of Europe’s most important non-native tree species due to its drought tolerance as well as timber quality and yield. To obtain superior seed from selected parental trees, breeding programs had been established in seed orchards. Douglas fir seed is used as source material for somatic embryogenesis with the aim to select elite genotypes invaluable for clonal mass propagation. To improve given protocols for somatic embryo initiation, we used immature Douglas fir zygotic embryos as explants and abscisic acid (ABA) as plant growth regulator in contrast to the application of auxins and cytokinins. With ABA supplementation, induction frequencies were slightly but in mean higher than with auxin/cytokinin, showing also a strong genotype effect. This offered the possibility to capture SE cultures from otherwise recalcitrant crosses. Furthermore, we observed remarkable differences between the two sets of plant growth regulators concerning the morphological development of the explants, including the absence of non-embryogenic callus by using ABA as inducer. This simplifies the detection of events and the handling of the obtained cultures. Nevertheless, a histological approach suggested, that the same competent cells are addressed by the different hormonal stimulation. Besides, we studied the influence of different points in time of cone harvest, two different basal media and different genetic backgrounds of the explants as well as the maturation ability of the induced embryogenic cultures. In sum, we were able to improve the first steps of somatic embryogenesis and to maintain a significantly higher number of high-value genotypes.