Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya

Background: The relationship between glucose-6-phosphate dehydrogenase (G6PD) deficiency and clinical phenomena such as primaquine-sensitivity and protection from severe malaria remains poorly defined, with past association studies yielding inconsistent and conflicting results. One possibility is that examination of a single genetic variant might underestimate the presence of true effects in the presence of unrecognized functional allelic diversity. Methods: We systematically examined this possibility in Kenya, conducting a fine-mapping association study of erythrocyte G6PD activity in 1828 Kenyan children across 30 polymorphisms at or around the G6PD locus. Results: We demonstrate a strong functional role for c.202G>A (rs1050828), which accounts for the majority of variance in enzyme activity observed (P=1.5 × 10-200, additive model). Additionally, we identify other common variants that exert smaller, intercorrelated effects independent of c.202G>A, and haplotype analyses suggest that each variant tags one of two haplotype motifs that are opposite in sequence identity and effect direction. We posit that these effects are of biological and possible clinical significance, specifically noting that c.376A>G (rs1050829) augments 202AG heterozygote risk for deficiency trait by two-fold (OR = 2.11 [1.12 - 3.84], P=0.014). Conclusions: Our results suggest that c.202G>A is responsible for the majority of the observed prevalence of G6PD deficiency trait in Kenya, but also identify a novel role for c.376A>G as a genetic modifier which marks a common haplotype that augments the risk conferred to 202AG heterozygotes, suggesting that variation at both loci merits consideration in genetic association studies probing G6PD deficiency-associated clinical phenotypes. </p

Resistance to wheat rusts identified in wheat/Amblyopyrum muticum chromosome introgressions

© 2020 The Authors. Crop Science © 2020 Crop Science Society of America Wheat (Triticum aestivum L.) rusts are a worldwide production problem. Plant breeders have used genetic resistance to combat these fungi. However, single-gene resistance is rapidly overcome as a result of frequent occurrence of new virulent fungal strains. Thus, a supply of new resistance sources is continually needed, and new resistance sources are limited within hexaploid wheat genetic stocks. Wild relatives are able to be a resource for new resistance genes but are hindered because of chromosome incapability with domesticated wheats. Twenty-eight double-haploid hexaploid wheat/Amblyopyrum muticum (Boiss.) Eig introgression lines, with introgressions covering the majority of the T genome, were evaluated for resistance to Puccinia triticina Erikss., P. graminis Pers.:Pers. f.sp. tritici Erikss. & E. Henning, and P. striiformis Westend. f.sp. tritici Erikss. At the seedling level, four lines were resistant to races of P. triticina, six lines were resistant to P. graminis, and 15 lines were resistant to P. striiformis. At the adult stage, 16 lines were resistant to P. triticina. Line 355 had resistance to all three rusts and line 161 had resistance to all tested races of P. triticina. Some of these lines will require further work to reduce the size of the introgressed segment; however, lines 92 and 355 have very small fragments and can be used directly as new resistance donors

Development of a New A –Genome-Specific Single Nucleotide Polymorphism Marker Set for the Molecular Characterization of Wheat– Introgression Lines

© 2019 The Author(s). Cultivated einkorn wheat (Triticum monococcum L. subsp. monococcum, 2n = 2x = 14, AmAm) and its wild relative T. monococcum subsp. aegilopoides are important sources of economically useful genes that can be exploited for wheat (Triticum aestivum L.) breeding. Einkorn has excellent resistance to fungal diseases and gene transfer is relatively simple via standard breeding methods. To fulfill the growing demand by modern prebreeding programs for a cost-effective high-throughpuprocedure for accurately detecting introgressed chromosomes or chromosome segments from T. monococcum into wheat, we used the Axiom Wheat-Relative Genotyping Array and developed a set of Am genome-specific exome-based single nucleotide polymorphism (SNP) markers suitable for rapid identification of T. monococcum chromatin in a wheat background. We identified 1247 polymorphic SNPs between T. monococcum and wheat. We identified 191 markers across all seven chromosomes of T. monococcum that are also present on an existing Triticum urartu Thum. ex Gandil. genetic map and potentially ordered them on the basis of the high macrocollinearity and conservation of marker order between T. monococcum and T. urartu. The marker set has been tested on leaf-rust-resistant BC3 F4 progenies of wheat–T. monococcum hybrids. Two markers (AX-94492165, AX-95073542) placed on the distal end of the chromosome arm 7AL detected a T. monococcum introgression into wheat. The SNP marker set thus proved highly effective in the identification of T. monococcum chromatin in a wheat background, offering a reliable method for screening and selecting wheat–T. monococcum introgression lines, a procedure that could significantly speed up prebreeding programs

Enhanced thylakoid photoprotection can increase yield and canopy radiation use efficiency in rice

High sunlight can raise plant growth rates but can potentially cause cellular damage. The likelihood of deleterious effects is lowered by a sophisticated set of photoprotective mechanisms, one of the most important being the controlled dissipation of energy from chlorophyll within photosystem II (PSII) measured as non-photochemical quenching (NPQ). Although ubiquitous, the role of NPQ in plant productivity remains uncertain because it momentarily reduces the quantum efficiency of photosynthesis. Here we used plants overexpressing the gene encoding a central regulator of NPQ, the protein PsbS, within a major crop species (rice) to assess the effect of photoprotection at the whole canopy scale. We accounted for canopy light interception, to our knowledge for the first time in this context. We show that in comparison to wild-type plants, psbS overexpressors increased canopy radiation use efficiency and grain yield in fluctuating light, demonstrating that photoprotective mechanisms should be altered to improve rice crop productivity

Development and validation of an exome-based SNP marker set for identification of the St, J ^r and J ^vs genomes of Thinopyrym intermedium in a wheat background

Thinopyrum intermedium (2n = 6x = 42, StJrJvs) is one of the most promising reservoirs of useful genes including tolerance to abiotic stresses, perenniality and disease resistance not available in the cultivated bread wheat. The transfer of genetic diversity from wild species to wheat offers valuable responses to the effects of climate change. The new array-based single-nucleotide polymorphism (SNP) marker technology provides cheap and easy-to-use molecular markers for marker-assisted selection (MAS) in wheat breeding programmes. Here, we focus on the generation of a new chromosome-specific SNP marker set that can be used to characterize and identify the Th. intermedium chromosomes or chromosome segments transferred into wheat. A progressive investigation of marker development was conducted using 187 various newly developed wheat–Th. intermedium introgression lines and the Axiom® Wheat-Relative Genotyping array. We employed molecular cytogenetic techniques to clarify the genome constitution of the Th. intermedium parental lines and validated 634 chromosome-specific SNPs. Our data confirmed the allohexaploid nature of Th. intermedium and demonstrated that the St genome-specific GISH signal and markers are present at the centromeric regions of chromosomes 1Jvs, 2Jvs, 3Jvs and 7Jvs. The SNP markers presented here will be introduced into current wheat improvement programmes, offering a significant speed-up in wheat breeding and making it possible to deal with the transfer of the full genetic potential of Th. intermedium into wheat

Malaria protection due to sickle haemoglobin depends on parasite genotype

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2-4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations

Natural variation in photosynthetic capacity, growth, and yield in 64 field-grown wheat genotypes

Increasing photosynthesis in wheat has been identified as an approach to enhance crop yield, with manipulation of key genes involved in electron transport and the Calvin cycle as one avenue currently being explored. However, natural variation in photosynthetic capacity is a currently unexploited genetic resource for potential crop improvement. Using gas-exchange analysis and protein analysis, the existing natural variation in photosynthetic capacity in a diverse panel of 64 elite wheat cultivars grown in the field was examined relative to growth traits, including biomass and harvest index. Significant variations in photosynthetic capacity, biomass, and yield were observed, although no consistent correlation was found between photosynthetic capacity of the flag leaf and grain yield when all cultivars were compared. The majority of the variation in photosynthesis could be explained by components related to maximum capacity and operational rates of CO2 assimilation, and to CO2 diffusion. Cluster analysis revealed that cultivars may have been bred unintentionally for desirable traits at the expense of photosynthetic capacity. These findings suggest that there is significant underutilized photosynthetic capacity among existing wheat varieties. Our observations are discussed in the context of exploiting existing natural variation in physiological processes for the improvement of photosynthesis in wheat. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as -23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.Peer reviewe

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Publisher Copyright: © 2021 Grau-Bové et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions.publishersversionpublishe