Genetic analysis identifies quantitative trait loci controlling rosette mineral concentrations in Arabidopsis thaliana under drought

• Rosettes of 25 Arabidopsis thaliana accessions and an Antwerp-1 (An-1) × Landsberg erecta (Ler) population of recombinant inbred lines (RILs) grown in optimal watering conditions (OWC) and water deficit conditions (WDC) were analysed for mineral concentrations to identify genetic loci involved in adaptation of mineral homeostasis to drought stress. • Correlations between mineral concentrations were determined for accessions and a quantitative trait locus (QTL) analysis was performed for the RIL population. • Plant growth and rosette mineral contents strongly decreased in WDC compared with OWC. Mineral concentrations also generally decreased, except for phosphorus (P), which remained constant, and potassium (K), which increased. Large variations in mineral concentrations were observed among accessions, mostly correlated with total rosette leaf area. Mineral concentration QTLs were identified in the RIL population, but only a few were common for both conditions. Clusters of mineral concentration QTLs often cosegregated with dry weight QTLs. • Water deficit has a strong effect on rosette mineral status. This is genetically determined and seems largely a pleiotropic effect of the reduction in growth. The low number of common mineral concentration QTLs, shared among different RIL populations, tissues and conditions in Arabidopsis, suggests that breeding for robust, mineral biofortified crops will be comple

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays