Potential and limits to unravel the genetic architecture and predict the variation of Fusarium head blight resistance in European winter wheat (Triticum aestivum L.)

Genome-wide mapping approaches in diverse populations are powerful tools to unravel the genetic architecture of complex traits. The main goals of our study were to investigate the potential and limits to unravel the genetic architecture and to identify the factors determining the accuracy of prediction of the genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) based on data collected with a diverse panel of 372 European varieties. The wheat lines were phenotyped in multi-location field trials for FHB resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide association mapping in combination with fivefold cross-validations and observed surprisingly high accuracies of prediction for marker-assisted selection based on the detected quantitative trait loci (QTLs). Using a random sample of markers not selected for marker–trait associations revealed only a slight decrease in prediction accuracy compared with marker-based selection exploiting the QTL information. The same picture was confirmed in a simulation study, suggesting that relatedness is a main driver of the accuracy of prediction in marker-assisted selection of FHB resistance. When the accuracy of prediction of three genomic selection models was contrasted for the three marker data sets, no significant differences in accuracies among marker platforms and genomic selection models were observed. Marker density impacted the accuracy of prediction only marginally. Consequently, genomic selection of FHB resistance can be implemented most cost-efficiently based on low- to medium-density SNP arrays.     

Antimicrobial benzodiazepine‐based short cationic peptidomimetics

Antimicrobial peptides (AMPs) appear to be good candidates for the development of new antibiotic drugs. We describe here the synthesis of peptidomimetic compounds that are based on a benzodiazepine scaffold flanked with positively charged and hydrophobic amino acids. These compounds mimic the essential properties of cationic AMPs. The new design possesses the benzodiazepine scaffold that is comprised of two glycine amino acids and which confers flexibility and aromatic hydrophobic ‘back’, and two arms used for further synthesis on solid phase for incorporation of charged and hydrophobic amino acids. This approach allowed us a better understanding of the influence of these features on the antimicrobial activity and selectivity. A novel compound was discovered which has MICs of 12.5 µg/ml against Staphylococcus aureus and 25 µg/ml against Escherichia coli, similar to the well‐known antimicrobial peptide MSI‐78. In contrast to MSI‐78, the above mentioned compound has lower lytic effect against mammalian red blood cells. These peptidomimetic compounds will pave the way for future design of potent synthetic mimics of AMPs for therapeutic and biomedical applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Modelling the genetic architecture of flowering time control in barley through nested association mapping

Background

Barley, globally the fourth most important cereal, provides food and beverages for humans and feed for animal husbandry. Maximizing grain yield under varying climate conditions largely depends on the optimal timing of flowering. Therefore, regulation of flowering time is of extraordinary importance to meet future food and feed demands. We developed the first barley nested association mapping (NAM) population, HEB-25, by crossing 25 wild barleys with one elite barley cultivar, and used it to dissect the genetic architecture of flowering time.

Results

Upon cultivation of 1,420 lines in multi-field trials and applying a genome-wide association study, eight major quantitative trait loci (QTL) were identified as main determinants to control flowering time in barley. These QTL accounted for 64% of the cross-validated proportion of explained genotypic variance (p_G). The strongest single QTL effect corresponded to the known photoperiod response gene Ppd-H1. After sequencing the causative part of Ppd-H1, we differentiated twelve haplotypes in HEB-25, whereof the strongest exotic haplotype accelerated flowering time by 11 days compared to the elite barley haplotype. Applying a whole genome prediction model including main effects and epistatic interactions allowed predicting flowering time with an unmatched accuracy of 77% of cross-validated p_G.

Conclusions

The elaborated causal models represent a fundamental step to explain flowering time in barley. In addition, our study confirms that the exotic biodiversity present in HEB-25 is a valuable toolbox to dissect the genetic architecture of important agronomic traits and to replenish the elite barley breeding pool with favorable, trait-improving exotic alleles.

     

Prospects and limits of marker imputation in quantitative genetic studies in European elite wheat (Triticum aestivum L.)

Background

The main goal of our study was to investigate the implementation, prospects, and limits of marker imputation for quantitative genetic studies contrasting map-independent and map-dependent algorithms. We used a diversity panel consisting of 372 European elite wheat (Triticum aestivum L.) varieties, which had been genotyped with SNP arrays, and performed intensive simulation studies.

Results

Our results clearly showed that imputation accuracy was substantially higher for map-dependent compared to map-independent methods. The accuracy of marker imputation depended strongly on the linkage disequilibrium between the markers in the reference panel and the markers to be imputed. For the decay of linkage disequilibrium present in European wheat, we concluded that around 45,000 markers are needed for low cost, low-density marker profiling. This will facilitate high imputation accuracy, also for rare alleles. Genomic selection and diversity studies profited only marginally from imputing missing values. In contrast, the power of association mapping increased substantially when missing values were imputed.

Conclusions

Imputing missing values is especially of interest for an economic implementation of association mapping in breeding populations.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1366-y) contains supplementary material, which is available to authorized users.     

Aromatic aldehyde and hydrazine activated peptide coated quantum dots for easy bioconjugation and live cell imaging

We present a robust scheme for preparation of semiconductor quantum dots (QDs) and cognate partners in a conjugation ready format. Our approach is based on bis-aryl hydrazone bond formation mediated by aromatic aldehyde and hydrazinonicotinate acetone hydrazone (HyNic) activated peptide coated quantum dots. We demonstrate controlled preparation of antibody--QD bioconjugates for specific targeting of endogenous epidermal growth factor receptors in breast cancer cells and for single QD tracking of transmembrane proteins via an extracellular epitope. The same approach was also used for optical mapping of RNA polymerases bound to combed genomic DNA in vitro.     

The Ras Antagonist,Farnesylthiosalicylic Acid (FTS), Decreases Fibrosis and Improves Muscle Strength in dy2J/dy2J Mouse Model of Muscular Dystrophy

The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy^2J/dy^2J mouse model of merosin deficient congenital muscular dystrophy. The dy^2J/dy^2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy^2J/dy^2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy^2J/dy^2J mouse model of congenital muscular dystrophy.     

Linkage disequilibrium in European elite maize germplasm investigated with SSRs

Information about the extent and genomic distribution of linkage disequilibrium (LD) is of fundamental importance for association mapping. The main objectives of this study were to (1) investigate genetic diversity within germplasm groups of elite European maize (Zea mays L.) inbred lines, (2) examine the population structure of elite European maize germplasm, and (3) determine the extent and genomic distribution of LD between pairs of simple sequence repeat (SSR) markers. We examined genetic diversity and LD in a cross section of European and US elite breeding material comprising 147 inbred lines genotyped with 100 SSR markers. For gene diversity within each group, significant (P<0.05) differences existed among the groups. The LD was significant (P<0.05) for 49% of the SSR marker pairs in the 80 flint lines and for 56% of the SSR marker pairs in the 57 dent lines. The ratio of linked to unlinked loci in LD was 1.1 for both germplasm groups. The high incidence of LD suggests that the extent of LD between SSR markers should allow the detection of marker-phenotype associations in a genome scan. However, our results also indicate that a high proportion of the observed LD is generated by forces, such as relatedness, population stratification, and genetic drift, which cause a high risk of detecting false positives in association mapping.     

Wheat genetic diversity trends during domestication and breeding

It has been claimed that plant breeding reduces genetic diversity in elite germplasm which could seriously jeopardize the continued ability to improve crops. The main objective of this study was to examine the loss of genetic diversity in spring bread wheat during (1) its domestication, (2) the change from traditional landrace cultivars (LCs) to modern breeding varieties, and (3) 50 years of international breeding. We studied 253 CIMMYT or CIMMYT-related modern wheat cultivars, LCs, and Triticum tauschii accessions, the D-genome donor of wheat, with 90 simple sequence repeat (SSR) markers dispersed across the wheat genome. A loss of genetic diversity was observed from T. tauschii to the LCs, and from the LCs to the elite breeding germplasm. Wheats genetic diversity was narrowed from 1950 to 1989, but was enhanced from 1990 to 1997. Our results indicate that breeders averted the narrowing of the wheat germplasm base and subsequently increased the genetic diversity through the introgression of novel materials. The LCs and T. tauschii contain numerous unique alleles that were absent in modern spring bread wheat cultivars. Consequently, both the LCs and T. tauschii represent useful sources for broadening the genetic base of elite wheat breeding germplasm.     

Gene expression profiling of mouse host response to Listeria monocytogenes infection

The purpose of this study was to evaluate gene expression profiles in the liver and blood for prediction of infection severity from Listeria monocytogenes (LM). Mice were injected with medium broth (control) or a nonlethal or lethal dose of LM and sacrificed 6 h later. Gene expression changes were determined using Affymetrix MGU74Av2 GeneChips and confirmed by real-time polymerase chain reaction analysis. We identified discernable genes whose gene expression profiles can be used in pattern recognition to predict and classify samples in differently treated groups, with >or=90% accuracy in liver samples and 80% accuracy in blood at prediction; however, different genes were predictive in each tissue. Our results suggest that gene expression profiling in response to LM in mice may be able to distinguish samples in groups with varying severity of infection and provide information in finding molecular mechanisms and early biomarkers for subsequent conventional clinical endpoints.