Multi-trait ensemble genomic prediction and simulations of recurrent selection highlight importance of complex trait genetic architecture for long-term genetic gains in wheat

Cereal crop breeders have achieved considerable genetic gain in genetically complex traits, such as grain yield, while maintaining genetic diversity. However, focus on selection for yield has negatively impacted other important traits. To better understand multi-trait selection within a breeding context, and how it might be optimized, we analysed genotypic and phenotypic data from a genetically diverse, 16-founder wheat multi-parent advanced generation inter-cross population. Compared to single-trait models, multi-trait ensemble genomic prediction models increased prediction accuracy for almost 90 % of traits, improving grain yield prediction accuracy by 3–52 %. For complex traits, non-parametric models (Random Forest) also outperformed simplified, additive models (LASSO), increasing grain yield prediction accuracy by 10–36 %. Simulations of recurrent genomic selection then showed that sustained greater forward prediction accuracy optimized long-term genetic gains. Simulations of selection on grain yield found indirect responses in related traits, involving optimized antagonistic trait relationships. We found multi-trait selection indices could effectively optimize undesirable relationships, such as the trade-off between grain yield and protein content, or combine traits of interest, such as yield and weed competitive ability. Simulations of phenotypic selection found that including Random Forest rather than LASSO genetic models, and multi-trait rather than single-trait models as the true genetic model accelerated and extended long-term genetic gain whilst maintaining genetic diversity. These results (i) suggest important roles of pleiotropy and epistasis in the wider context of wheat breeding programmes, and (ii) provide insights into mechanisms for continued genetic gain in a limited genepool and optimization of multiple traits for crop improvement

Limited haplotype diversity underlies polygenic trait architecture across 70 years of wheat breeding

Background Selection has dramatically shaped genetic and phenotypic variation in bread wheat. We can assess the genomic basis of historical phenotypic changes, and the potential for future improvement, using experimental populations that attempt to undo selection through the randomizing effects of recombination. Results We bred the NIAB Diverse MAGIC multi-parent population comprising over 500 recombinant inbred lines, descended from sixteen historical UK bread wheat varieties released between 1935 and 2004. We sequence the founders’ genes and promoters by capture, and the MAGIC population by low-coverage whole-genome sequencing. We impute 1.1 M high-quality SNPs that are over 99% concordant with array genotypes. Imputation accuracy only marginally improves when including the founders’ genomes as a haplotype reference panel. Despite capturing 73% of global wheat genetic polymorphism, 83% of genes cluster into no more than three haplotypes. We phenotype 47 agronomic traits over 2 years and map 136 genome-wide significant associations, concentrated at 42 genetic loci with large and often pleiotropic effects. Around half of these overlap known quantitative trait loci. Most traits exhibit extensive polygenicity, as revealed by multi-locus shrinkage modelling. Conclusions Our results are consistent with a gene pool of low haplotypic diversity, containing few novel loci of large effect. Most past, and projected future, phenotypic changes arising from existing variation involve fine-scale shuffling of a few haplotypes to recombine dozens of polygenic alleles of small effect. Moreover, extensive pleiotropy means selection on one trait will have unintended consequences, exemplified by the negative trade-off between yield and protein content, unless selection and recombination can break unfavorable trait-trait associations

Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley

Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions), comprising of 95 photoperiod-sensitive (Ppd-H1) and 123 accessions with reduced photoperiod sensitivity (ppd-H1) to long-day (LD) through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH) conditions (LD; 16/8 h; ∼20/∼16°C day/night). Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs) chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS). GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1) and BFL (BARLEY FLORICAULA/LEAFY) genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley

Relationship between psychological and biological factors and physical activity and exercise behaviour in Filipino students

The aim of the present study was threefold. Firstly, it investigated whether a general measure or specific measure of motivational orientation was better in describing the relationship between motivation and exercise behaviour. Secondly, it examined the relationship between the four most popular indirect methods of body composition assessment and physical activity and exercise patterns. Thirdly, the interaction between motivation and body composition on physical activity and exercise behaviour was explored in a sample of 275 Filipino male and female students. Males were found to have higher levels of exercise whereas females had higher levels of physical activity. Furthermore, general self-motivation together with body weight and percentage body fat were found to be the best predictor of exercise behaviour whereas the tension/pressure subscale of the ‘Intrinsic Motivation Inventory’ (IMI) was the best predictor of levels of physical activity. However, significant gender differences were observed. That is, for the males only self-motivation and for the females only body weight and BMI predicted exercise behaviour. Also, tension/pressure predicted physical activity levels for the females but not the males. No inverse relationship was found between the four body composition measures and exercise and physical activity behaviour. The results support the notion that the psychobiological approach might be particularly relevant for high intensity exercise situations but also highlights some important gender differences. Finally, the results of this study emphasise the need for more cross-cultural research

Dissecting the genetic basis of wheat blast resistance in the Brazilian wheat cultivar BR 18-Terena.

Background: Wheat blast, caused by Magnaporthe oryzae Triticum (MoT) pathotype, is a global threat to wheat (Triticum aestivum L.) production. Few blast resistance (R) genes have been identified to date, therefore assessing potential sources of resistance in wheat is important. The Brazilian wheat cultivar BR 18-Terena is considered one of the best sources of resistance to blast and has been widely used in Brazilian breeding programmes, however the underlying genetics of this resistance are unknown. Results: BR 18-Terena was used as the common parent in the development of two recombinant inbred line (RIL) F6 populations with the Brazilian cultivars Anahuac 75 and BRS 179. Populations were phenotyped for resistance at the seedling and heading stage using the sequenced MoT isolate BR32, with transgressive segregation being observed. Genetic maps containing 1779 and 1318 markers, were produced for the Anahuac 75 × BR 18-Terena and BR 18- Terena × BRS 179 populations, respectively. Five quantitative trait loci (QTL) associated with seedling resistance, on chromosomes 2B, 4B (2 QTL), 5A and 6A, were identified, as were four QTL associated with heading stage resistance (1A, 2B, 4A and 5A). Seedling and heading stage QTL did not co-locate, despite a significant positive correlation between these traits, indicating that resistance at these developmental stages is likely to be controlled by different genes. BR 18-Terena provided the resistant allele for six QTL, at both developmental stages, with the largest phenotypic effect conferred by a QTL being 24.8% suggesting that BR 18-Terena possesses quantitative resistance. Haplotype analysis of 100 Brazilian wheat cultivars indicates that 11.0% of cultivars already possess a BR 18-Terenalike haplotype for more than one of the identified heading stage QTL. Conclusions: This study suggests that BR 18-Terena possesses quantitative resistance to wheat blast, with nine QTL associated with resistance at either the seedling or heading stage being detected. Wheat blast resistance is also largely tissue-specific. Identification of durable quantitative resistances which can be combined with race-specific R gene-mediated resistance is critical to effectively control wheat blast. Collectively, this work facilitates markerassisted selection to develop new varieties for cultivation in regions at risk from this emerging disease

Multi-trait ensemble genomic prediction and simulations of recurrent selection highlight importance of complex trait genetic architecture for long-term genetic gains in wheat

Cereal crop breeders have achieved considerable genetic gain in genetically complex traits, such as grain yield, while maintaining genetic diversity. However, focus on selection for yield has negatively impacted other important traits. To better understand multi-trait selection within a breeding context, and how it might be optimized, we analysed genotypic and phenotypic data from a genetically diverse, 16-founder wheat multi-parent advanced generation inter-cross population. Compared to single-trait models, multi-trait ensemble genomic prediction models increased prediction accuracy for almost 90 % of traits, improving grain yield prediction accuracy by 3–52 %. For complex traits, non-parametric models (Random Forest) also outperformed simplified, additive models (LASSO), increasing grain yield prediction accuracy by 10–36 %. Simulations of recurrent genomic selection then showed that sustained greater forward prediction accuracy optimized long-term genetic gains. Simulations of selection on grain yield found indirect responses in related traits, involving optimized antagonistic trait relationships. We found multi-trait selection indices could effectively optimize undesirable relationships, such as the trade-off between grain yield and protein content, or combine traits of interest, such as yield and weed competitive ability. Simulations of phenotypic selection found that including Random Forest rather than LASSO genetic models, and multi-trait rather than single-trait models as the true genetic model accelerated and extended long-term genetic gain whilst maintaining genetic diversity. These results (i) suggest important roles of pleiotropy and epistasis in the wider context of wheat breeding programmes, and (ii) provide insights into mechanisms for continued genetic gain in a limited genepool and optimization of multiple traits for crop improvement

Quantitative genomic analysis of RecA protein binding during DNA double-strand break repair reveals RecBCD action in vivo

International audienceUnderstanding molecular mechanisms in the context of living cells requires the development of new methods of in vivo biochemical analysis to complement established in vitro biochemistry. A critically important molecular mechanism is genetic recombination, required for the beneficial reassortment of genetic information and for DNA double-strand break repair (DSBR). Central to recom-bination is the RecA (Rad51) protein that assembles into a spiral filament on DNA and mediates genetic exchange. Here we have developed a method that combines chromatin immunoprecipita-tion with next-generation sequencing (ChIP-Seq) and mathematical modeling to quantify RecA protein binding during the active repair of a single DSB in the chromosome of Escherichia coli. We have used quantitative genomic analysis to infer the key in vivo molecular parameters governing RecA loading by the helicase/ nuclease RecBCD at recombination hot-spots, known as Chi. Our genomic analysis has also revealed that DSBR at the lacZ locus causes a second RecBCD-mediated DSBR event to occur in the terminus region of the chromosome, over 1 Mb away. homologous recombination | mechanistic modelling | DNA repair | RecA

Incidence of Diabetes in the Working Population in Spain: Results from the ICARIA Cohort

INTRODUCTION: Our objective was to evaluate the incidence of type 2 diabetes mellitus (T2DM) in a working population in Spain and to assess associations between its development and several risk factors. METHODS: The ICARIA (Ibermutuamur CArdiovascular RIsk Assessment) cohort (n = 627,523) includes ~3% of Spanish workers. This analysis was undertaken in individuals whose glycaemic status during the index period (May 2004-December 2007) was determined to be normal or indicative of prediabetes [fasting plasma glucose (FPG) 100-125 mg/dl] and who had at least one FPG measurement taken 9 months after a first measurement during follow-up (May 2004-June 2014) (n = 380,366). T2DM patients were defined as those with an FPG ? 126 mg/day and those who had already been diagnosed with T2DM or were taking antihyperglycaemic medications. RESULTS: The incidence rate of T2DM was 5.0 [95% confidence interval (CI) 4.9-5.1] cases per 1000 person-years. Under multivariate logistic regression analysis, the factor showing the strongest association with the occurrence of T2DM was the baseline FPG level, with the likelihood of T2DM almost doubling for every 5 mg/dl increase in baseline FPG between 100 and < 126 mg/dl. The presence of other cardiometabolic risk factors and being a blue-collar worker were also significantly associated with the occurrence of T2DM. CONCLUSIONS: The incidence of T2DM in the working population was within the range encountered in the general population and prediabetes was found to be the strongest risk factor for the development of diabetes. The workplace is an appropriate and feasible setting for the assessment of easily measurable risk factors, such as the presence of prediabetes and other cardiometabolic factors, to facilitate the early detection of individuals at higher risk of diabetes and the implementation of diabetes prevention programmes

Evolutionary relationships among barley and <i>Arabidopsis</i> core circadian clock and clock-associated genes

The circadian clock regulates a multitude of plant developmental and metabolic processes. In crop species, it contributes significantly to plant performance and productivity and to the adaptation and geographical range over which crops can be grown. To understand the clock in barley and how it relates to the components in the Arabidopsis thaliana clock, we have performed a systematic analysis of core circadian clock and clock-associated genes in barley, Arabidopsis and another eight species including tomato, potato, a range of monocotyledonous species and the moss, Physcomitrella patens. We have identified orthologues and paralogues of Arabidopsis genes which are conserved in all species, monocot/dicot differences, species-specific differences and variation in gene copy number (e.g. gene duplications among the various species). We propose that the common ancestor of barley and Arabidopsis had two-thirds of the key clock components identified in Arabidopsis prior to the separation of the monocot/dicot groups. After this separation, multiple independent gene duplication events took place in both monocot and dicot ancestors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00239-015-9665-0) contains supplementary material, which is available to authorized users

RecBCD coordinates repair of two ends at a DNA double-strand break, preventing aberrant chromosome amplification

DNA double-strand break (DSB) repair is critical for cell survival. A diverse range of organisms from bacteria to humans rely on homologous recombination for accurate DSB repair. This requires both coordinate action of the two ends of a DSB and stringent control of the resultant DNA replication to prevent unwarranted DNA amplification and aneuploidy. In Escherichia coli, RecBCD enzyme is responsible for the initial steps of homologous recombination. Previous work has revealed recD mutants to be nuclease defective but recombination proficient. Despite this proficiency, we show here that a recD null mutant is defective for the repair of a two-ended DSB and that this defect is associated with unregulated chromosome amplification and defective chromosome segregation. Our results demonstrate that RecBCD plays an important role in avoiding this amplification by coordinating the two recombining ends in a manner that prevents divergent replication forks progressing away from the DSB site