Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well as abnormalities of the brain, skeletal system, movement/gait, and behavior were variable features. Phenotyping of knocked down wars-1 in a C. elegans model showed depletion is associated with defects in germ cell development. A wars1 knockout vertebrate model recapitulates the human clinical phenotypes, confirms variant pathogenicity and uncovers evidence implicating the p.Met1? variant as potentially impacting an exon critical for normal hearing. Together, our findings provide consolidating evidence for biallelic disruption of WARS1 as causal for an autosomal recessive neurodevelopmental syndrome and present a vertebrate model that recapitulates key phenotypes observed in patients. This article is protected by copyright. All rights reserved

Improved genetic map identified major QTLs for drought tolerance- and iron deficiency tolerance-related traits in groundnut

A deep understanding of the genetic control of drought tolerance and iron deficiency tolerance is essential to hasten the process of developing improved varieties with higher tolerance through genomics-assisted breeding. In this context, an improved genetic map with 1205 loci was developed spanning 2598.3 cM with an average 2.2 cM distance between loci in the recombinant inbred line (TAG 24 × ICGV 86031) population using high-density 58K single nucleotide polymorphism (SNP) “Axiom_Arachis” array. Quantitative trait locus (QTL) analysis was performed using extensive phenotyping data generated for 20 drought tolerance- and two iron deficiency tolerance-related traits from eight seasons (2004–2015) at two locations in India, one in Niger, and one in Senegal. The genome-wide QTL discovery analysis identified 19 major main-effect QTLs with 10.0–33.9% phenotypic variation explained (PVE) for drought tolerance- and iron deficiency tolerance- related traits. Major main-effect QTLs were detected for haulm weight (20.1% PVE), SCMR (soil plant analytical development (SPAD) chlorophyll meter reading, 22.4% PVE), and visual chlorosis rate (33.9% PVE). Several important candidate genes encoding glycosyl hydrolases; malate dehydrogenases; microtubule-associated proteins; and transcription factors such as MADS-box, basic helix-loop-helix (bHLH), NAM, ATAF, and CUC (NAC), and myeloblastosis (MYB) were identified underlying these QTL regions. The putative function of these genes indicated their possible involvement in plant growth, development of seed and pod, and photosynthesis under drought or iron deficiency conditions in groundnut. These genomic regions and candidate genes, after validation, may be useful to develop molecular markers for deploying genomics-assisted breeding for enhancing groundnut yield under drought stress and iron-deficient soil conditions

Proline over-accumulation alleviates salt stress and protects photosynthetic and antioxidant enzyme activities in transgenic sorghum [Sorghum bicolor (L.) Moench]

Shoot-tip derived callus cultures of Sorghum bicolor were transformed by Agrobacterium tumefaciens as well as by bombardment methods with the mutated pyrroline-5-carboxylate synthetase (P5CSF129A) gene encoding the key enzyme for proline biosynthesis from glutamate. The transgenics were selfed for three generations and T4 plants were examined for 100 mM NaCl stress tolerance in pot conditions. The effect of salt stress on chlorophyll and carotenoid contents, photosynthetic rate, stomatal conductance, internal carbon dioxide concentration, transpiration rates, intrinsic transpiration and water use efficiencies, proline content, MDA levels, and antioxidant enzyme activities were evaluated in 40-day-old transgenic lines and the results were compared with untransformed control plants. The results show that chlorophyll content declines by 65% in untransformed controls compared to 30–38% loss (significant at P < 0.05) in transgenics but not carotenoid levels. Photosynthetic rate (PSII activity) was reduced in untransformed controls almost completely, while it declined by 62–88% in different transgenic lines. Salinity induced ca 100% stomatal closure in untransformed plants, while stomatal conductance was decreased only by 64–81% in transgenics after 4 days. The intercellular CO2 decreased by ca 30% in individual transgenic lines. Malondialdehyde (MDA) content was lower in transgenics compared to untransformed controls. The activities of superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6) and glutathione reductase (GR; EC1.8.1.7) were quantified in leaves exposed to 100 mM NaCl stress and found higher in transgenics. The results suggest that transgenic lines were able to cope better with salt stress than untransformed controls by protecting photosynthetic and antioxidant enzyme activities

Breeding and molecular approaches for evolving drought-tolerant soybeans

Soybean [Glycine max (L.) Merr] is an agronomically important oilseed crop in the world and an important source of protein and oil for both humans and animals. In addition, soybean is also becoming a major crop for bio-diesel production. Therefore, demand for soybean is increasing continuously worldwide. Soybean enriches the soil by fixing atmospheric nitrogen through symbiotic interaction with Rhizobia. With increasing challenges posed by climate change, it is predicted that incidents of drought will be more frequent and severe and it will further reduce crop yields. Abiotic stresses such as drought cause severe losses to soybean productivity worldwide by adversely affecting the plant growth, development, and yield. Introgression of genes controlling drought adaptive traits, yields related traits and root system architecture traits by breeding and molecular approaches will be very useful for enhancing drought stress tolerance in soybean, leading to cultivar development. Elucidation of function of genes and their integration in soybean genotypes by molecular breeding and genomic approaches and utilizing robust phenotyping tools to evaluate drought adaptive traits will be crucial for understanding response of soybean plants to drought stress. Recent advances in genomics lead identification, functional characterization, and introgression of genes associated with adaptation of soybean plants to drought stress. In order to perform genetic and genomic analysis, molecular markers have been employed on RIL or F2 populations. In addition, the genome typified with single nucleotide polymorphisms (SNPs) and its utilization in molecular breeding applications like QTL mapping, positional cloning, association mapping studies, genomic selection and genome editing is gaining impetus. Thus, the rapid development of soybean genomics and transcriptomics has provided tremendous opportunity for the genetic improvement of soybean for drought tolerance with yield stability

A multifunctional mutagenesis system for analysis of gene function in zebrafish

10.1534/g3.114.015842G3: Genes, Genomes, Genetics561283-129