Ph1 gene

Primary hyperoxaluria (PH) is an autosomal recessive disorder of oxalate metabolism caused by pathogenic variants in either of three genes (AGXT, GRHPR or HOGA1). The study aimed at characterizing the clinical phenotypes as well as the genotypic spectrum of PH in Egypt. We screened 25 Egyptian patients suspected of PH for the three responsible genes by Sanger sequencing. We diagnosed 20 patients from 18 unrelated families, in which the natural history, family history, clinical features and genotypes were evaluated...

Human lactate dehydrogenase A (hLDHA) is one of the main enzymes involved in the pathway of oxalate synthesis in human liver and seems to contribute to the pathogenesis of disorders with endogenous oxalate overproduction, such as primary hyperoxaluria (PH), a rare life-threatening genetic disease. Recent published results on the knockdown of LDHA gene expression as a safe strategy to ameliorate oxalate build-up in PH patients are encouraging for an approach of hLDHA inhibition by small molecules as a potential pharmacological treatment...

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months...

Aegilops tauschii , the D-genome donor of hexaploid wheat, provides a source of genetic variation that could be used for tetraploid (durum) wheat improvement. In addition to the genes for wheat quality on the D-genome, which differentiate between bread and durum wheats in terms of end-use properties, genes coding for resistances to biotic and abiotic stresses are also present on the D-genome which would be useful in durum wheat. The introgression of Ae. tauschii into durum wheat, however, requires cytogenetic manipulation to induce homoeologous chromosome pairing to promote recombination...

Background: The discovery of biological subphenotypes in acute respiratory distress syndrome (ARDS) might offer a new approach to ARDS in general and possibly targeted treatment, but little is known about the underlying biology yet. To validate our recently described ovine ARDS phenotypes model, we compared a subset of messenger ribonucleic acid (mRNA) markers in leukocytes as reported before to display differential expression between human ARDS subphenotypes to the expression in lung tissue in our ovine ARDS phenotypes model (phenotype 1 (Ph1): hypoinflammatory; phenotype 2 (Ph2): hyperinflammatory)...

Effective utilization of genetic diversity in wild relatives to improve wheat requires recombination between wheat and alien chromosomes. However, this is suppressed by the Pairing homoeologous gene, Ph1 , on the long arm of wheat chromosome 5B. A deletion mutant of the Ph1 locus ( ph1b ) has been used widely to induce homoeologous recombination in wheat × alien hybrids. However, the original ph1b mutation, developed in Chinese Spring (CS) background has poor agronomic performance. Hence, alien introgression lines are first backcrossed with adapted wheat genotypes and after this step, alien chromosome segments are introduced into breeding lines...

BACKGROUND: Primary hyperoxaluria (PH) is a rare heterogeneous, autosomal recessive disorder of glyoxylate metabolism. It is characterized by excessive hepatic production of oxalate resulting in a wide spectrum of clinical, imaging, and functional presentation. The characteristic features of PH comprise of recurrent urolithiasis, renal stones, and/or nephrocalcinosis. Three known types of PH have been identified PH1, PH2, and PH3. Pathogenic variants in AGXT, GRHPR, and HOGA1 cause the phenotypic expression of PH...

Primary hyperoxaluria type I (PH1) is caused by AGXT gene mutations that decrease the functional activity of alanine:glyoxylate aminotransferase. A build-up of the enzyme's substrate, glyoxylate, results in excessive deposition of calcium oxalate crystals in the renal tract, leading to debilitating renal failure. Oxidation of glycolate by glycolate oxidase (or hydroxy acid oxidase 1, HAO1) is a major cellular source of glyoxylate, and siRNA studies have shown phenotypic rescue of PH1 by the knockdown of HAO1, representing a promising inhibitor target...

Wheat is a globally vital crop, but its limited genetic variation creates a challenge for breeders aiming to maintain or accelerate agricultural improvements over time. Introducing novel genes and alleles from wheat's wild relatives into the wheat breeding pool via introgression lines is an important component of overcoming this low variation but is constrained by poor genomic resolution and limited understanding of the genomic impact of introgression breeding programmes. By sequencing 17 hexaploid wheat/Ambylopyrum muticum introgression lines and the parent lines, we have precisely pinpointed the borders of introgressed segments, most of which occur within genes...

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism characterized by marked hepatic overproduction of oxalate due to deficiency of hepatic peroxisomal alanine-glyoxylate aminotransferase caused by AGXT gene mutation. One major hallmark of PH1 in developed as well as developing countries (DC) is the diagnostic delay. Notably in DC, where the disease is most prevalent and probably underdiagnosed, there are many challenges in PH1 diagnosis and management, with economic constrains and ethical concerns...

Oxalate crystals in the kidney were first described in 1925. Since then, many major milestones have been reached in the understanding of genetic primary hyperoxaluria(s). Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease due to a mutation in the AGXT gene, which encodes the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), inducing excess oxalate production and further kidney stones, nephrocalcinosis and chronic kidney disease (CKD). Symptoms and age at diagnosis of PH1 vary dramatically, from the most severe infantile forms leading to end-stage kidney disease (ESKD) during the first months of life to the less severe adult forms with moderate CKD and recurrent kidney stones...

Primary hyperoxaluria type 1 (PH1) is a rare and severe autosomal recessive disease of oxalate metabolism, resulting from a mutation in the AGXT gene that encodes the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT). Until recently, treatment of PH1 was supportive, consisting of intensive hyperhydration, use of crystallization inhibitors (citrate and neutral phosphorus), in a subset of responsive PH1 patients' pharmacologic doses of vitamin B6 (pyridoxine), and kidney and liver transplantation when patients progressed to kidney failure...

Nephrolithiasis (NL) and urolithiasis (UL) are usual reasons for hospitalization and presentation in pediatric outpatient departments and their incidence continues to rise worldwide. In Morocco, a previous epidemiological study done in the Fez region between January 2003 and November 2013 reported a prevalence of 0.83% of childhood UL. In two studies, heritability accounted for almost half of all NL or nephrocalcinosis (NC) prevalence. Genetic factors must be considered in the etiological diagnosis of urinary lithiasis in Morocco since the frequency of consanguineous marriages is high...

Crested wheatgrass ( Agropyron cristatum L. Gaertn., genome P), included in the Triticeae tribe (family Poaceae), is one of the most important grasses in temperate regions. It has been valued as a donor of important agronomic traits for wheat improvement, including tolerance to cold, drought, and high salinity, as well as resistance to leaf rust, stripe rust, and powdery mildew. For successful incorporation of beneficial alleles into wheat, it is essential that recombination between wheat and A. cristatum chromosomes occurs...

Primary hyperoxaluria (PH) is a group of diseases due to mutations in genes coding for enzymes involved in oxalate metabolism. Three types of PH are identified depending on the gene mutated. Type 1 is the most frequent with 80% of the cases, while PH2 and PH3 are rarer. The severity of renal involvement varies between the three types. Indeed, between 60% and 80% of PH1 but only 20% of PH2 patients will reach end-stage kidney disease. In PH3 patients, dialysis is uncommon. Because oxalate clearance is impaired in CKD patients, oxalate can precipitate in various organs leading to systemic oxalosis...

Human structure-specific recognition protein 1 (hSSRP1) is an essential component of the FACT (facilitates chromatin transcription) complex, which participates in nucleosome disassembly and reassembly during gene transcription and DNA replication and repair. Many functions, including nuclear localization, histone chaperone activity, DNA binding, and interaction with cellular proteins, are attributed to hSSRP1, which contains multiple well-defined domains, including four pleckstrin homology (PH) domains and a high-mobility group (HMG) domain with two flanking disordered regions...

Many species, including most flowering plants, are polyploid, possessing multiple genomes. During polyploidisation, fertility is preserved via the evolution of mechanisms to control the behaviour of these multiple genomes during meiosis. On the polyploidisation of wheat, the major meiotic gene ZIP4 duplicated and diverged, with the resulting new gene TaZIP4-B2 being inserted into chromosome 5B. Previous studies showed that this TaZIP4-B2 promotes pairing and synapsis between wheat homologous chromosomes, whilst suppressing crossover between related (homoeologous) chromosomes...

Plant cytogenetic studies have provided essential knowledge on chromosome behavior during meiosis, contributing to our understanding of this complex process. In this review, we describe in detail the meiotic process in auto- and allopolyploids from the onset of prophase I through pairing, recombination, and bivalent formation, highlighting recent findings on the genetic control and mode of action of specific proteins that lead to diploid-like meiosis behavior in polyploid species. During the meiosis of newly formed polyploids, related chromosomes (homologous in autopolyploids; homologous and homoeologous in allopolyploids) can combine in complex structures called multivalents...

Primary hyperoxaluria (PH) is a family of ultra-rare autosomal recessive inherited disorders of hepatic glyoxylate metabolism characterized by oxalate overproduction. Nedosiran is an RNA interference agent that inhibits hepatic lactate dehydrogenase, the enzyme responsible for the common, final step of oxalate production in all three genetic subtypes of PH. Here, we assessed in a two-part, randomized, single-ascending-dose, phase 1 study (PHYOX1) the safety, pharmacokinetics, pharmacodynamics, and exposure-response of subcutaneous nedosiran in 25 healthy participants (Group A) and 18 patients with PH1 or PH2 (Group B)...

In filamentous fungi, gene silencing by RNA interference (RNAi) shapes many biological processes, including pathogenicity. Recently, fungal small RNAs (sRNAs) have been shown to act as effectors that disrupt gene activity in interacting plant hosts, thereby undermining their defence responses. We show here that the devastating mycotoxin-producing ascomycete Fusarium graminearum (Fg) utilizes DICER-like (DCL)-dependent sRNAs to target defence genes in two Poaceae hosts, barley (Hordeum vulgare, Hv) and Brachypodium distachyon (Bd)...