Measuring Iron Bioavailability in Peas via Cell Culture Assay, Chicken (Gallus gallus) Feeding Study, and Athlete Trials

Non-Peer ReviewedField pea is a valuable crop for delivery of high protein content, slowly digested carbohydrates, fiber, and a high density of vitamins and minerals, including iron. High iron levels are of particular importance in human diets, as anemia is an ongoing challenge for many individuals. Iron levels in seeds at harvest are mitigated by nutrient levels in the soil and crop genetics. However, although high iron levels may be measured in some pea varieties, there may be limited absorption during digestion due to presence of the naturally occurring plant molecule phytate, which chelates with iron, zinc, and other cations. The Warkentin team, at the University of Saskatchewan, have bred agronomically viable pea lines that are low in phytate. Collaborating with scientists at Cornell University, Ithaca, NY, these lines were tested for iron bioavailability by the Caco-2 cell culture assay and a chicken feeding study. This talk will summarize the research to date and share plans for upcoming human trials involving endurance-trained women and Paralympic athletes, two groups particularly prone to anemia. Link to Video Presentation: https://youtu.be/Y__lg9K3a3

Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI's Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits

Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs

The bioavailability of iron fortified in whole grain parboiled rice

The present study was to evaluate the bioavailability of iron (Fe) fortified in parboiled rice grain, expressed as Fe uptake by Caco-2 cells after in vitro digestion. The bioavailability of Fe-fortified in the rice grain was closely and positively correlated with increasing concentrations of Fe in the grains of the three cultivars (r = 0.96**). The uptakes of the Fe-fortified in parboiled rice milled for 120 s (34.2, 47.7 and 107 ng ferritin mg protein in three cultivars, respectively) were well above those of the unfortified raw (6.1, 4.9 and 5.7 ng ferritin mg protein) or parboiled rice (4.7, 3.6 and 4.4 ng ferritin mg protein), the high Fe rice line IR68144-2B-3-2-2 (4.0 ng ferritin mg protein) and popular Jasmine rice cultivar KDML 105 (3.9 ng ferritin mg protein). Increasing milling time and rinsing the Fe-fortified parboiled rice decreased Fe bioavailability, due to their negative effects on total Fe concentrations in the parboiled rice grains, but uptakes were still well above that of their unfortified raw or parboiled rice grains. Rinsing or washing the Fe-fortified and milled rice grains decreased the bioavailability to 85 ng ferritin mg protein in the YRF cultivar, compared to about 100 ng ferritin mg protein in its non-rinsed grains. Dilute acid-extractable (DAE) Fe was linearly, positively correlated with the uptake of Fe assessed by the in vitro digestion/Caco-2 cell technique (r = 0.90**), which can be used as a rapid method for optimizing levels of bioavailable Fe to be fortified in the parboiled rice by parboiled-rice mills if this Fe-fortification technique should be adopted in south and southeast Asia