Smart breeding driven by big data, artificial intelligence, and integrated genomic-enviromic prediction.

The first paradigm of plant breeding involves direct selection-based phenotypic observation, followed by predictive breeding using statistical models for quantitative traits constructed based on genetic experimental design and, more recently, by incorporation of molecular marker genotypes. However, plant performance or phenotype (P) is determined by the combined effects of genotype (G), envirotype (E), and genotype by environment interaction (GEI). Phenotypes can be predicted more precisely by training a model using data collected from multiple sources, including spatiotemporal omics (genomics, phenomics, and enviromics across time and space). Integration of 3D information profiles (G-P-E), each with multidimensionality, provides predictive breeding with both tremendous opportunities and great challenges. Here, we first review innovative technologies for predictive breeding. We then evaluate multidimensional information profiles that can be integrated with a predictive breeding strategy, particularly envirotypic data, which have largely been neglected in data collection and are nearly untouched in model construction. We propose a smart breeding scheme, integrated genomic-enviromic prediction (iGEP), as an extension of genomic prediction, using integrated multiomics information, big data technology, and artificial intelligence (mainly focused on machine and deep learning). We discuss how to implement iGEP, including spatiotemporal models, environmental indices, factorial and spatiotemporal structure of plant breeding data, and cross-species prediction. A strategy is then proposed for prediction-based crop redesign at both the macro (individual, population, and species) and micro (gene, metabolism, and network) scales. Finally, we provide perspectives on translating smart breeding into genetic gain through integrative breeding platforms and open-source breeding initiatives. We call for coordinated efforts in smart breeding through iGEP, institutional partnerships, and innovative technological support.

Incorporating male sterility increases hybrid maize yield in low input African farming systems.

Maize is a staple crop in sub-Saharan Africa, but yields remain sub-optimal. Improved breeding and seed systems are vital to increase productivity. We describe a hybrid seed production technology that will benefit seed companies and farmers. This technology improves efficiency and integrity of seed production by removing the need for detasseling. The resulting hybrids segregate 1:1 for pollen production, conserving resources for grain production and conferring a 200 kg ha-1 benefit across a range of yield levels. This represents a 10% increase for farmers operating at national average yield levels in sub-Saharan Africa. The yield benefit provided by fifty-percent non-pollen producing hybrids is the first example of a single gene technology in maize conferring a yield increase of this magnitude under low-input smallholder farmer conditions and across an array of hybrid backgrounds. Benefits to seed companies will provide incentives to improve smallholder farmer access to higher quality seed. Demonstrated farmer preference for these hybrids will help drive their adoption.

Identification of Genomic Regions Associated with Agronomic and Disease Resistance Traits in a Large Set of Multiple DH Populations.

Breeding maize lines with the improved level of desired agronomic traits under optimum and drought conditions as well as increased levels of resistance to several diseases such as maize lethal necrosis (MLN) is one of the most sustainable approaches for the sub-Saharan African region. In this study, 879 doubled haploid (DH) lines derived from 26 biparental populations were evaluated under artificial inoculation of MLN, as well as under well-watered (WW) and water-stressed (WS) conditions for grain yield and other agronomic traits. All DH lines were used for analyses of genotypic variability, association studies, and genomic predictions for the grain yield and other yield-related traits. Genome-wide association study (GWAS) using a mixed linear FarmCPU model identified SNPs associated with the studied traits i.e., about seven and eight SNPs for the grain yield; 16 and 12 for anthesis date; seven and eight for anthesis silking interval; 14 and 5 for both ear and plant height; and 15 and 5 for moisture under both WW and WS environments, respectively. Similarly, about 13 and 11 SNPs associated with gray leaf spot and turcicum leaf blight were identified. Eleven SNPs associated with senescence under WS management that had depicted drought-stress-tolerant QTLs were identified. Under MLN artificial inoculation, a total of 12 and 10 SNPs associated with MLN disease severity and AUDPC traits, respectively, were identified. Genomic prediction under WW, WS, and MLN disease artificial inoculation revealed moderate-to-high prediction accuracy. The findings of this study provide useful information on understanding the genetic basis for the MLN resistance, grain yield, and other agronomic traits under MLN artificial inoculation, WW, and WS conditions. Therefore, the obtained information can be used for further validation and developing functional molecular markers for marker-assisted selection and for implementing genomic prediction to develop superior elite lines.

Discovery and Validation of a Recessively Inherited Major-Effect QTL Conferring Resistance to Maize Lethal Necrosis (MLN) Disease.

Maize lethal necrosis (MLN) is a viral disease with a devastating effect on maize production. Developing and deploying improved varieties with resistance to the disease is important to effectively control MLN; however, little is known about the causal genes and molecular mechanism(s) underlying MLN resistance. Screening thousands of maize inbred lines revealed KS23-5 and KS23-6 as two of the most promising donors of MLN resistance alleles. KS23-5 and KS23-6 lines were earlier developed at the University of Hawaii, United States, on the basis of a source population constituted using germplasm from Kasetsart University, Thailand. Both linkage mapping and association mapping approaches were used to discover and validate genomic regions associated with MLN resistance. Selective genotyping of resistant and susceptible individuals within large F2 populations coupled with genome-wide association study identified a major-effect QTL (qMLN06_157) on chromosome 6 for MLN disease severity score and area under the disease progress curve values in all three F2 populations involving one of the KS23 lines as a parent. The major-effect QTL (qMLN06_157) is recessively inherited and explained 55%-70% of the phenotypic variation with an approximately 6 Mb confidence interval. Linkage mapping in three F3 populations and three F2 populations involving KS23-5 or KS23-6 as one of the parents confirmed the presence of this major-effect QTL on chromosome 6, demonstrating the efficacy of the KS23 allele at qMLN06.157 in varying populations. This QTL could not be identified in population that was not derived using KS23 lines. Validation of this QTL in six F2 populations with 20 SNPs closely linked with qMLN06.157 was further confirmed its consistent expression across populations and its recessive nature of inheritance. On the basis of the consistent and effective resistance afforded by the KS23 allele at qMLN06.157, the QTL can be used in both marker-assisted forward breeding and marker-assisted backcrossing schemes to improve MLN resistance of breeding populations and key lines for eastern Africa.

Development of high-resolution multiple-SNP arrays for genetic analyses and molecular breeding through genotyping by target sequencing and liquid chip.

Genotyping platforms, as critical supports for genomics, genetics, and molecular breeding, have been well implemented at national institutions/universities in developed countries and multinational seed companies that possess high-throughput, automatic, large-scale, and shared facilities. In this study, we integrated an improved genotyping by target sequencing (GBTS) system with capture-in-solution (liquid chip) technology to develop a multiple single-nucleotide polymorphism (mSNP) approach in which mSNPs can be captured from a single amplicon. From one 40K maize mSNP panel, we developed three types of markers (40K mSNPs, 251K SNPs, and 690K haplotypes), and generated multiple panels with various marker densities (1K-40K mSNPs) by sequencing at different depths. Comparative genetic diversity analysis was performed with genic versus intergenic markers and di-allelic SNPs versus non-typical SNPs. Compared with the one-amplicon-one-SNP system, mSNPs and within-mSNP haplotypes are more powerful for genetic diversity detection, linkage disequilibrium decay analysis, and genome-wide association studies. The technologies, protocols, and application scenarios developed for maize in this study will serve as a model for the development of mSNP arrays and highly efficient GBTS systems in animals, plants, and microorganisms.

Genetic dissection of Striga hermonthica (Del.) Benth. resistance via genome-wide association and genomic prediction in tropical maize germplasm.

KEY MESSAGE: Genome-wide association revealed that resistance to Striga hermonthica is influenced by multiple genomic regions with moderate effects. It is possible to increase genetic gains from selection for Striga resistance using genomic prediction. Striga hermonthica (Del.) Benth., commonly known as the purple witchweed or giant witchweed, is a serious problem for maize-dependent smallholder farmers in sub-Saharan Africa. Breeding for Striga resistance in maize is complicated due to limited genetic variation, complexity of resistance and challenges with phenotyping. This study was conducted to (i) evaluate a set of diverse tropical maize lines for their responses to Striga under artificial infestation in three environments in Kenya; (ii) detect quantitative trait loci associated with Striga resistance through genome-wide association study (GWAS); and (iii) evaluate the effectiveness of genomic prediction (GP) of Striga-related traits. An association mapping panel of 380 inbred lines was evaluated in three environments under artificial Striga infestation in replicated trials and genotyped with 278,810 single-nucleotide polymorphism (SNP) markers. Genotypic and genotype x environment variations were significant for measured traits associated with Striga resistance. Heritability estimates were moderate (0.42) to high (0.92) for measured traits. GWAS revealed 57 SNPs significantly associated with Striga resistance indicator traits and grain yield (GY) under artificial Striga infestation with low to moderate effect. A set of 32 candidate genes physically near the significant SNPs with roles in plant defense against biotic stresses were identified. GP with different cross-validations revealed that prediction of performance of lines in new environments is better than prediction of performance of new lines for all traits. Predictions across environments revealed high accuracy for all the traits, while inclusion of GWAS-detected SNPs led to slight increase in the accuracy. The item-based collaborative filtering approach that incorporates related traits evaluated in different environments to predict GY and Striga-related traits outperformed GP for Striga resistance indicator traits. The results demonstrated the polygenic nature of resistance to S. hermonthica, and that implementation of GP in Striga resistance breeding could potentially aid in increasing genetic gain for this important trait.

Genetic Dissection of Resistance to Gray Leaf Spot by Combining Genome-Wide Association, Linkage Mapping, and Genomic Prediction in Tropical Maize Germplasm.

Gray leaf spot (GLS) is one of the major maize foliar diseases in sub-Saharan Africa. Resistance to GLS is controlled by multiple genes with additive effect and is influenced by both genotype and environment. The objectives of the study were to dissect the genetic architecture of GLS resistance through linkage mapping and genome-wide association study (GWAS) and assessing the potential of genomic prediction (GP). We used both biparental populations and an association mapping panel of 410 diverse tropical/subtropical inbred lines that were genotyped using genotype by sequencing. Phenotypic evaluation in two to four environments revealed significant genotypic variation and moderate to high heritability estimates ranging from 0.43 to 0.69. GLS was negatively and significantly correlated with grain yield, anthesis date, and plant height. Linkage mapping in five populations revealed 22 quantitative trait loci (QTLs) for GLS resistance. A QTL on chromosome 7 (qGLS7-105) is a major-effect QTL that explained 28.2% of phenotypic variance. Together, all the detected QTLs explained 10.50, 49.70, 23.67, 18.05, and 28.71% of phenotypic variance in doubled haploid (DH) populations 1, 2, 3, and F3 populations 4 and 5, respectively. Joint linkage association mapping across three DH populations detected 14 QTLs that individually explained 0.10-15.7% of phenotypic variance. GWAS revealed 10 significantly (p < 9.5 × 10-6) associated SNPs distributed on chromosomes 1, 2, 6, 7, and 8, which individually explained 6-8% of phenotypic variance. A set of nine candidate genes co-located or in physical proximity to the significant SNPs with roles in plant defense against pathogens were identified. GP revealed low to moderate prediction correlations of 0.39, 0.37, 0.56, 0.30, 0.29, and 0.38 for within IMAS association panel, DH pop1, DH pop2, DH pop3, F3 pop4, and F3 po5, respectively, and accuracy was increased substantially to 0.84 for prediction across three DH populations. When the diversity panel was used as training set to predict the accuracy of GLS resistance in biparental population, there was 20-50% reduction compared to prediction within populations. Overall, the study revealed that resistance to GLS is quantitative in nature and is controlled by many loci with a few major and many minor effects. The SNPs/QTLs identified by GWAS and linkage mapping can be potential targets in improving GLS resistance in breeding programs, while GP further consolidates the development of high GLS-resistant lines by incorporating most of the major- and minor-effect genes.

Combination of Linkage Mapping, GWAS, and GP to Dissect the Genetic Basis of Common Rust Resistance in Tropical Maize Germplasm.

Common rust (CR) caused by Puccina sorghi is one of the destructive fungal foliar diseases of maize and has been reported to cause moderate to high yield losses. Providing CR resistant germplasm has the potential to increase yields. To dissect the genetic architecture of CR resistance in maize, association mapping, in conjunction with linkage mapping, joint linkage association mapping (JLAM), and genomic prediction (GP) was conducted on an association-mapping panel and five F3 biparental populations using genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs). Analysis of variance for the biparental populations and the association panel showed significant genotypic and genotype x environment (GXE) interaction variances except for GXE of Pop4. Heritability (h2) estimates were moderate with 0.37-0.45 for the individual F3 populations, 0.45 across five populations and 0.65 for the association panel. Genome-wide association study (GWAS) analyses revealed 14 significant marker-trait associations which individually explained 6-10% of the total phenotypic variances. Individual population-based linkage analysis revealed 26 QTLs associated with CR resistance and together explained 14-40% of the total phenotypic variances. Linkage mapping revealed seven QTLs in pop1, nine QTL in pop2, four QTL in pop3, five QTL in pop4, and one QTL in pop5, distributed on all chromosomes except chromosome 10. JLAM for the 921 F3 families from five populations detected 18 QTLs distributed in all chromosomes except on chromosome 8. These QTLs individually explained 0.3 to 3.1% and together explained 45% of the total phenotypic variance. Among the 18 QTL detected through JLAM, six QTLs, qCR1-78, qCR1-227, qCR3-172, qCR3-186, qCR4-171, and qCR7-137 were also detected in linkage mapping. GP within population revealed low to moderate correlations with a range from 0.19 to 0.51. Prediction correlation was high with r = 0.78 for combined analysis of the five F3 populations. Prediction of biparental populations by using association panel as training set reveals positive correlations ranging from 0.05 to 0.22, which encourages to develop an independent but related population as a training set which can be used to predict diverse but related populations. The findings of this study provide valuable information on understanding the genetic basis of CR resistance and the obtained information can be used for developing functional molecular markers for marker-assisted selection and for implementing GP to improve CR resistance in tropical maize.

Hybrid Breeding for MLN Resistance: Heterosis, Combining Ability, and Hybrid Prediction.

Prior knowledge on heterosis and quantitative genetic parameters on maize lethal necrosis (MLN) can help the breeders to develop numerous resistant or tolerant hybrids with optimum resources. Our objectives were to (1) estimate the quantitative genetic parameters for MLN disease severity, (2) investigate the efficiency of the prediction of hybrid performance based on parental per se and general combining ability (GCA) effects, and (3) examine the potential of hybrid prediction for MLN resistance or tolerance based on markers. Fifty elite maize inbred lines were selected based on their response to MLN under artificial inoculation. Crosses were made in a half diallel mating design to produce 307 F1 hybrids. All hybrids were evaluated in MLN quarantine facility in Naivasha, Kenya for two seasons under artificial inoculation. All 50 inbreds were genotyped with genotyping-by-sequencing (GBS) SNPs. The phenotypic variation was significant for all traits and the heritability was moderate to high. We observed that hybrids were superior to the mean performance of the parents for disease severity (-14.57%) and area under disease progress curve (AUDPC) (14.9%). Correlations were significant and moderate between line per se and GCA; and mean of parental value with hybrid performance for both disease severity and AUDPC value. Very low and negative correlation was observed between parental lines marker based genetic distance and heterosis. Nevertheless, the correlation of GCA effects was very high with hybrid performance which can suggests as a good predictor of MLN resistance. Genomic prediction of hybrid performance for MLN is high for both traits. We therefore conclude that there is potential for prediction of hybrid performance for MLN. Overall, the estimated quantitative genetic parameters suggest that through targeted approach, it is possible to develop outstanding lines and hybrids for MLN resistance.

Enhancing Genetic Gain through Genomic Selection: From Livestock to Plants.

Although long-term genetic gain has been achieved through increasing use of modern breeding methods and technologies, the rate of genetic gain needs to be accelerated to meet humanity's demand for agricultural products. In this regard, genomic selection (GS) has been considered most promising for genetic improvement of the complex traits controlled by many genes each with minor effects. Livestock scientists pioneered GS application largely due to livestock's significantly higher individual values and the greater reduction in generation interval that can be achieved in GS. Large-scale application of GS in plants can be achieved by refining field management to improve heritability estimation and prediction accuracy and developing optimum GS models with the consideration of genotype-by-environment interaction and non-additive effects, along with significant cost reduction. Moreover, it would be more effective to integrate GS with other breeding tools and platforms for accelerating the breeding process and thereby further enhancing genetic gain. In addition, establishing an open-source breeding network and developing transdisciplinary approaches would be essential in enhancing breeding efficiency for small- and medium-sized enterprises and agricultural research systems in developing countries. New strategies centered on GS for enhancing genetic gain need to be developed.

Genome-Wide Analyses and Prediction of Resistance to MLN in Large Tropical Maize Germplasm.

Maize lethal necrosis (MLN), caused by co-infection of maize chlorotic mottle virus and sugarcane mosaic virus, can lead up to 100% yield loss. Identification and validation of genomic regions can facilitate marker assisted breeding for resistance to MLN. Our objectives were to identify marker-trait associations using genome wide association study and assess the potential of genomic prediction for MLN resistance in a large panel of diverse maize lines. A set of 1400 diverse maize tropical inbred lines were evaluated for their response to MLN under artificial inoculation by measuring disease severity or incidence and area under disease progress curve (AUDPC). All lines were genotyped with genotyping by sequencing (GBS) SNPs. The phenotypic variation was significant for all traits and the heritability estimates were moderate to high. GWAS revealed 32 significantly associated SNPs for MLN resistance (at p < 1.0 × 10-6). For disease severity, these significantly associated SNPs individually explained 3-5% of the total phenotypic variance, whereas for AUDPC they explained 3-12% of the total proportion of phenotypic variance. Most of significant SNPs were consistent with the previous studies and assists to validate and fine map the big quantitative trait locus (QTL) regions into few markers' specific regions. A set of putative candidate genes associated with the significant markers were identified and their functions revealed to be directly or indirectly involved in plant defense responses. Genomic prediction revealed reasonable prediction accuracies. The prediction accuracies significantly increased with increasing marker densities and training population size. These results support that MLN is a complex trait controlled by few major and many minor effect genes.

Genetic architecture of maize chlorotic mottle virus and maize lethal necrosis through GWAS, linkage analysis and genomic prediction in tropical maize germplasm.

KEY MESSAGE: Analysis of the genetic architecture of MCMV and MLN resistance in maize doubled-haploid populations revealed QTLs with major effects on chromosomes 3 and 6 that were consistent across genetic backgrounds and environments. Two major-effect QTLs, qMCMV3-108/qMLN3-108 and qMCMV6-17/qMLN6-17, were identified as conferring resistance to both MCMV and MLN. Maize lethal necrosis (MLN) is a serious threat to the food security of maize-growing smallholders in sub-Saharan Africa. The ability of the maize chlorotic mottle virus (MCMV) to interact with other members of the Potyviridae causes severe yield losses in the form of MLN. The objective of the present study was to gain insights and validate the genetic architecture of resistance to MCMV and MLN in maize. We applied linkage mapping to three doubled-haploid populations and a genome-wide association study (GWAS) on 380 diverse maize lines. For all the populations, phenotypic variation for MCMV and MLN was significant, and heritability was moderate to high. Linkage mapping revealed 13 quantitative trait loci (QTLs) for MCMV resistance and 12 QTLs conferring MLN resistance. One major-effect QTL, qMCMV3-108/qMLN3-108, was consistent across populations for both MCMV and MLN resistance. Joint linkage association mapping (JLAM) revealed 18 and 21 main-effect QTLs for MCMV and MLN resistance, respectively. Another major-effect QTL, qMCMV6-17/qMLN6-17, was detected for both MCMV and MLN resistance. The GWAS revealed a total of 54 SNPs (MCMV-13 and MLN-41) significantly associated (P ≤ 5.60 × 10-05) with MCMV and MLN resistance. Most of the GWAS-identified SNPs were within or adjacent to the QTLs detected through linkage mapping. The prediction accuracy for within populations as well as the combined populations is promising; however, the accuracy was low across populations. Overall, MCMV resistance is controlled by a few major and many minor-effect loci and seems more complex than the genetic architecture for MLN resistance.

Discovery and validation of genomic regions associated with resistance to maize lethal necrosis in four biparental populations.

In sub-Saharan Africa, maize is the key determinant of food security for smallholder farmers. The sudden outbreak of maize lethal necrosis (MLN) disease is seriously threatening the maize production in the region. Understanding the genetic basis of MLN resistance is crucial. In this study, we used four biparental populations applied linkage mapping and joint linkage mapping approaches to identify and validate the MLN resistance-associated genomic regions. All populations were genotyped with low to high density markers and phenotyped in multiple environments against MLN under artificial inoculation. Phenotypic variation for MLN resistance was significant and heritability was moderate to high in all four populations for both early and late stages of disease infection. Linkage mapping revealed three major quantitative trait loci (QTL) on chromosomes 3, 6, and 9 that were consistently detected in at least two of the four populations. Phenotypic variance explained by a single QTL in each population ranged from 3.9% in population 1 to 43.8% in population 2. Joint linkage association mapping across three populations with three biometric models together revealed 16 and 10 main effect QTL for MLN-early and MLN-late, respectively. The QTL identified on chromosomes 3, 5, 6, and 9 were consistent with the QTL identified by linkage mapping. Ridge regression best linear unbiased prediction with five-fold cross-validation revealed high accuracy for prediction across populations for both MLN-early and MLN-late. Overall, the study discovered and validated the presence of major effect QTL on chromosomes 3, 6, and 9 which can be potential candidates for marker-assisted breeding to improve the MLN resistance.

Genome-Wide Association Mapping and Genomic Prediction Analyses Reveal the Genetic Architecture of Grain Yield and Flowering Time Under Drought and Heat Stress Conditions in Maize.

Drought stress (DS) is a major constraint to maize yield production. Heat stress (HS) alone and in combination with DS are likely to become the increasing constraints. Association mapping and genomic prediction (GP) analyses were conducted in a collection of 300 tropical and subtropical maize inbred lines to reveal the genetic architecture of grain yield and flowering time under well-watered (WW), DS, HS, and combined DS and HS conditions. Out of the 381,165 genotyping-by-sequencing SNPs, 1549 SNPs were significantly associated with all the 12 trait-environment combinations, the average PVE (phenotypic variation explained) by these SNPs was 4.33%, and 541 of them had a PVE value greater than 5%. These significant associations were clustered into 446 genomic regions with a window size of 20 Mb per region, and 673 candidate genes containing the significantly associated SNPs were identified. In addition, 33 hotspots were identified for 12 trait-environment combinations and most were located on chromosomes 1 and 8. Compared with single SNP-based association mapping, the haplotype-based associated mapping detected fewer number of significant associations and candidate genes with higher PVE values. All the 688 candidate genes were enriched into 15 gene ontology terms, and 46 candidate genes showed significant differential expression under the WW and DS conditions. Association mapping results identified few overlapped significant markers and candidate genes for the same traits evaluated under different managements, indicating the genetic divergence between the individual stress tolerance and the combined drought and HS tolerance. The GP accuracies obtained from the marker-trait associated SNPs were relatively higher than those obtained from the genome-wide SNPs for most of the target traits. The genetic architecture information of the grain yield and flowering time revealed in this study, and the genomic regions identified for the different trait-environment combinations are useful in accelerating the efforts on rapid development of the stress-tolerant maize germplasm through marker-assisted selection and/or genomic selection.

Enhancing genetic gain in the era of molecular breeding.

As one of the important concepts in conventional quantitative genetics and breeding, genetic gain can be defined as the amount of increase in performance that is achieved annually through artificial selection. To develop pro ducts that meet the increasing demand of mankind, especially for food and feed, in addition to various industrial uses, breeders are challenged to enhance the potential of genetic gain continuously, at ever higher rates, while they close the gaps that remain between the yield potential in breeders' demonstration trials and the actual yield in farmers' fields. Factors affecting genetic gain include genetic variation available in breeding materials, heritability for traits of interest, selection intensity, and the time required to complete a breeding cycle. Genetic gain can be improved through enhancing the potential and closing the gaps, which has been evolving and complemented with modern breeding techniques and platforms, mainly driven by molecular and genomic tools, combined with improved agronomic practice. Several key strategies are reviewed in this article. Favorable genetic variation can be unlocked and created through molecular and genomic approaches including mutation, gene mapping and discovery, and transgene and genome editing. Estimation of heritability can be improved by refining field experiments through well-controlled and precisely assayed environmental factors or envirotyping, particularly for understanding and controlling spatial heterogeneity at the field level. Selection intensity can be significantly heightened through improvements in the scale and precision of genotyping and phenotyping. The breeding cycle time can be shortened by accelerating breeding procedures through integrated breeding approaches such as marker-assisted selection and doubled haploid development. All the strategies can be integrated with other widely used conventional approaches in breeding programs to enhance genetic gain. More transdisciplinary approaches, team breeding, will be required to address the challenge of maintaining a plentiful and safe food supply for future generations. New opportunities for enhancing genetic gain, a high efficiency breeding pipeline, and broad-sense genetic gain are also discussed prospectively.

Genome-wide association and genomic prediction of resistance to maize lethal necrosis disease in tropical maize germplasm.

KEY MESSAGE: Genome-wide association analysis in tropical and subtropical maize germplasm revealed that MLND resistance is influenced by multiple genomic regions with small to medium effects. The maize lethal necrosis disease (MLND) caused by synergistic interaction of Maize chlorotic mottle virus and Sugarcane mosaic virus, and has emerged as a serious threat to maize production in eastern Africa since 2011. Our objective was to gain insights into the genetic architecture underlying the resistance to MLND by genome-wide association study (GWAS) and genomic selection. We used two association mapping (AM) panels comprising a total of 615 diverse tropical/subtropical maize inbred lines. All the lines were evaluated against MLND under artificial inoculation. Both the panels were genotyped using genotyping-by-sequencing. Phenotypic variation for MLND resistance was significant and heritability was moderately high in both the panels. Few promising lines with high resistance to MLND were identified to be used as potential donors. GWAS revealed 24 SNPs that were significantly associated (P < 3 × 10(-5)) with MLND resistance. These SNPs are located within or adjacent to 20 putative candidate genes that are associated with plant disease resistance. Ridge regression best linear unbiased prediction with five-fold cross-validation revealed higher prediction accuracy for IMAS-AM panel (0.56) over DTMA-AM (0.36) panel. The prediction accuracy for both within and across panels is promising; inclusion of MLND resistance associated SNPs into the prediction model further improved the accuracy. Overall, the study revealed that resistance to MLND is controlled by multiple loci with small to medium effects and the SNPs identified by GWAS can be used as potential candidates in MLND resistance breeding program.

The heritability of antinociception II: pharmacogenetic mediation of three over-the-counter analgesics in mice.

Chromosomal loci containing genes affecting antinociceptive sensitivity to morphine have been identified, but virtually nothing is known about the genetic mediation of sensitivity to over-the-counter analgesics. Such knowledge would be of great clinical interest, as prodigious interindividual variability has been noted in the efficacy of these ubiquitously used drugs. In the present study, we assessed heritability and genetic correlations among three over-the-counter analgesics in mice of 12 inbred mouse strains on the 0.9% acetic acid (i.p.) writhing test. Analgesics included the centrally acting analgesic, acetaminophen (150 mg/kg, s.c.), and the nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin (40 mg/kg, s.c.) and lysine-acetylsalicylic acid (800 mg/kg, s.c.). Significant strain differences in sensitivity to each of the drugs were observed, with narrow-sense heritability estimates ranging from 23 to 45%. Similar strains were sensitive and resistant, respectively, to the two NSAIDs (r(s) = 0.64). In contrast, a completely different pattern of sensitivities was observed for acetaminophen, implying genetic dissociation (r(s) = 0.29 and 0.02) compared with the NSAIDs. Additional experiments were performed on two strains, C57BL/6 and DBA/2, with extreme sensitivities to acetaminophen. Plasma acetaminophen levels in these strains were not significantly different during the time of antinociception assessment, suggesting the existence of genetic factors affecting acetaminophen pharmacodynamics rather than pharmacokinetics.