Earlier studies were focused on the genetics of temperate and tropical maize under drought. We identified genetic loci and their association with functional mechanisms in 240 accessions of subtropical maize using a high-density marker set under water stress.

Globally, one-third of the population is affected by iron (Fe) and zinc (Zn) deficiency, which is severe in developing and underdeveloped countries where cereal-based diets predominate. The genetic biofortification approach is the most sustainable and one of the cost-effective ways to address Fe and Zn malnutrition. Maize is a major source of nutrition in sub-Saharan Africa, South Asia and Latin America. Understanding systems’ biology and the identification of genes involved in Fe and Zn homeostasis facilitate the development of Fe- and Zn-enriched maize. We conducted a genome-wide transcriptome assay in maize inbred SKV616, under –Zn, –Fe and –Fe–Zn stresses. The results revealed the differential expression of several genes related to the mugineic acid pathway, metal transporters, photosynthesis, phytohormone and carbohydrate metabolism. We report here Fe and Zn deficiency-mediated changes in the transcriptome, root length, stomatal conductance, transpiration rate and reduced rate of photosynthesis. Furthermore, the presence of multiple regulatory elements and/or the co-factor nature of Fe and Zn in enzymes indicate their association with the differential expression and opposite regulation of several key gene(s). The differentially expressed candidate genes in the present investigation would help in breeding for Fe and Zn efficient and kernel Fe- and Zn-rich maize cultivars through gene editing, transgenics and molecular breeding.

Maize is an increasingly important food crop in southeast Asia. The elucidation of its genetic architecture, accomplished by exploring quantitative trait loci and useful alleles in various lines across numerous breeding programs, is therefore of great interest. The present study aimed to characterize subtropical maize lines using high-quality SNPs distributed throughout the genome.

Intrauterine smoke (IUS) exposure during early childhood has been associated with a number of negative health consequences, including reduced lung function and asthma susceptibility. The biological mechanisms underlying these associations have not been established. MicroRNAs regulate the expression of numerous genes involved in lung development. Thus, investigation of the impact of IUS on miRNA expression during human lung development may elucidate the impact of IUS on post-natal respiratory outcomes. We sought to investigate the effect of IUS exposure on miRNA expression during early lung development. We hypothesized that miRNA–mRNA networks are dysregulated by IUS during human lung development and that these miRNAs may be associated with future risk of asthma and allergy. Human fetal lung samples from a prenatal tissue retrieval program were tested for differential miRNA expression with IUS exposure (measured using placental cotinine concentration). RNA was extracted and miRNA-sequencing was performed. We performed differential expression using IUS exposure, with covariate adjustment. We also considered the above model with an additional sex-by-IUS interaction term, allowing IUS effects to differ by male and female samples. Using paired gene expression profiles, we created sex-stratified miRNA–mRNA correlation networks predictive of IUS using DIABLO. We additionally evaluated whether miRNAs were associated with asthma and allergy outcomes in a cohort of childhood asthma. We profiled pseudoglandular lung miRNA in n = 298 samples, 139 (47%) of which had evidence of IUS exposure. Of 515 miRNAs, 25 were significantly associated with intrauterine smoke exposure (q-value < 0.10). The IUS associated miRNAs were correlated with well-known asthma genes (e.g., ORM1-Like Protein 3, ORDML3) and enriched in disease-relevant pathways (oxidative stress). Eleven IUS-miRNAs were also correlated with clinical measures (e.g., Immunoglobulin E andlungfunction) in children with asthma, further supporting their likely disease relevance. Lastly, we found substantial differences in IUS effects by sex, finding 95 significant IUS-miRNAs in male samples, but only four miRNAs in female samples. The miRNA–mRNA correlation networks were predictive of IUS (AUC = 0.78 in males and 0.86 in females) and suggested that IUS-miRNAs are involved in regulation of disease-relevant genes (e.g., A disintegrin and metalloproteinase domain 19 (ADAM19), LBH regulator of WNT signaling (LBH)) and sex hormone signaling (Coactivator associated methyltransferase 1(CARM1)). Our study demonstrated differential expression of miRNAs by IUS during early prenatal human lung development, which may be modified by sex. Based on their gene targets and correlation to clinical asthma and atopy outcomes, these IUS-miRNAs may be relevant for subsequent allergy and asthma risk. Our study provides insight into the impact of IUS in human fetal lung transcriptional networks and on the developmental origins of asthma and allergic disorders.

Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology. The purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation. We used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways. MiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients. LOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

Rationale: Pediatric asthma is heterogeneous, with varied clinical presentations and treatment responses. Metabolomic profiling may uncover shared and unique biological mechanisms across clinical traits that characterize pediatric asthma. Objectives: To characterize the varied clinical presentation of pediatric asthma by examining the metabolome’s relationship with 22 clinical traits, categorized into five phenotypic domains: airway hyperresponsiveness, atopy, lung function, blood eosinophils, and blood neutrophils. Methods: Metabolomic profiling was conducted on plasma samples from children in the Childhood Asthma Management Program study (n = 953) and the Genetic Epidemiology of Asthma in Costa Rica Study (n = 1,155). We identified domain-specific and multidomain metabolites using a fixed-effect meta-analysis of generalized linear models between metabolites and 22 clinical traits. Metabolomic risk scores (MRSs) were developed to summarize the metabolic processes for each domain at the patient level. Measurements and Main Results: There were 154 unique metabolites significantly associated with at least one of 22 clinical traits (q < 0.05). Histamine and kynurenine were significant across four domains, whereas seven metabolites—12,13-diHOME, azelate, sebacate, PC(P-36:0)/PC(O-36:1), taurine, nudifloramide, and niacinamide—were significant across three. Notable domain-specific metabolites include n-oleoyl dopamine for airway hyperresponsiveness, 9-cis-retinoic acid for lung function, phosphatidylcholines for blood eosinophils, and 2-hydroxybutyric acid for blood neutrophils. Domain specific MRS exhibited distinct patterns across the metaboendotypes, highlighting the ability of this approach to refine asthma subtypes. Conclusions: This study demonstrated the power of the metabolome to capture the heterogeneity in the clinical presentation of pediatric asthma and to develop clinically relevant MRSs that inform our understanding of specific metabotypes to guide targeted treatment approaches.