scholarly journals Molecular structure of soybean E-genes and their functional mutations

2020 ◽  
pp. 3-13
Author(s):  
O. Okhrymovych ◽  
◽  
S. Chebotar ◽  
G. Chebotar ◽  
D. Zharikova ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Genetic Network ◽  
Structural Features ◽  
Loss Of Function ◽  
Nucleotide Substitutions ◽  
Early Maturity ◽  
E Gene ◽  
Wide Range

In this review, we discuss features of the molecular structure of known E-loci (early maturity) and their involvement in signaling to plant flowering, depending on the sensitivity of soybean genotypes to the photoperiod. These loci contribute to the adaptation of plants to a wide range of natural conditions due to mutations in genes and QTL that control flowering time. At the molecular level, E-genes are significantly different in structural features, origin and function. The lenghth of the identified genes range from one exon to 525 bp encoding the transcription factor (E1), up to 14 exons and about 20 kb for the GmGIa gene (E2). Among the functional mutations that in most cases lead to partial or complete loss of function, there are single-nucleotide substitutions or deletions, insertions of transposon-like sequences that can lead to amino acid substitutions in the protein, shift of the reading frame, appearance of the premature stop-codon. E-gene products are receptors of signals coming from the environment and they participate in signaling pathways that control the photoperiod. The overall impact and interactions between E-genes have not been fully studied yet, the molecular structure was investigated only for E1-E4, for which a genetic network of interactions was proposed, while at the same time five loci (E6-E9 and E11) were only mapped on soybean chromosomes, and the existence of a separate E5 locus has not yet been established. In eight of the 11 E-loci, the dominant allele causes late flowering. Also there is a pleiotropic effect of E-gene alleles on yield, plant height, stress resistance, and response to low temperatures. Knowledge of the allelic state of only some of the 11 genes is not sufficient. A comprehensive understanding of the functioning of the photoperiodic genetic response network is needed. E-genes are genetic determinants that can be used during selection and creation of new varieties with programmed rates of development.

scholarly journals Cis-Segregation of c.1171C>T Stop Codon (p.R391*) in SERPINC1 Gene and c.1691G>A Transition (p.R506Q) in F5 Gene and Selected GWAS Multilocus Approach in Inherited Thrombophilia

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 934
Author(s):  
Donato Gemmati ◽  
Giovanna Longo ◽  
Eugenia Franchini ◽  
Juliana Araujo Silva ◽  
Ines Gallo ◽  
...  
Keyword(s):  
At Risk ◽  
Stop Codon ◽  
Association Studies ◽  
Premature Stop Codon ◽  
Large Family ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Gene Markers ◽  
Inherited Thrombophilia ◽  
Fv Leiden

Inherited thrombophilia (e.g., venous thromboembolism, VTE) is due to rare loss-of-function mutations in anticoagulant factors genes (i.e., SERPINC1, PROC, PROS1), common gain-of-function mutations in procoagulant factors genes (i.e., F5, F2), and acquired risk conditions. Genome Wide Association Studies (GWAS) recently recognized several genes associated with VTE though gene defects may unpredictably remain asymptomatic, so calculating the individual genetic predisposition is a challenging task. We investigated a large family with severe, recurrent, early-onset VTE in which two sisters experienced VTE during pregnancies characterized by a perinatal in-utero thrombosis in the newborn and a life-saving pregnancy-interruption because of massive VTE, respectively. A nonsense mutation (CGA > TGA) generating a premature stop-codon (c.1171C>T; p.R391*) in the exon 6 of SERPINC1 gene (1q25.1) causing Antithrombin (AT) deficiency and the common missense mutation (c.1691G>A; p.R506Q) in the exon 10 of F5 gene (1q24.2) (i.e., FV Leiden; rs6025) were coinherited in all the symptomatic members investigated suspecting a cis-segregation further confirmed by STR-linkage-analyses [i.e., SERPINC1 IVS5 (ATT)5–18, F5 IVS2 (AT)6–33 and F5 IVS11 (GT)12–16] and SERPINC1 intragenic variants (i.e., rs5878 and rs677). A multilocus investigation of blood-coagulation balance genes detected the coexistence of FV Leiden (rs6025) in trans with FV HR2-haplotype (p.H1299R; rs1800595) in the aborted fetus, and F11 rs2289252, F12 rs1801020, F13A1 rs5985, and KNG1 rs710446 in the newborn and other members. Common selected gene variants may strongly synergize with less common mutations tuning potential life-threatening conditions when combined with rare severest mutations. Merging classic and newly GWAS-identified gene markers in at risk families is mandatory for VTE risk estimation in the clinical practice, avoiding partial risk score evaluation in unrecognized at risk patients.

scholarly journals Loss-of-function in IRF2BPL is associated with neurological phenotypes

2018 ◽  
Author(s):  
Paul C. Marcogliese ◽  
Vandana Shashi ◽  
Rebecca C. Spillmann ◽  
Nicholas Stong ◽  
Jill A. Rosenfeld ◽  
...  
Keyword(s):  
Nervous System ◽  
Population Genomics ◽  
Stop Codon ◽  
Ectopic Expression ◽  
Premature Stop Codon ◽  
Model Organism ◽  
Global Developmental Delay ◽  
Mendelian Disease ◽  
Loss Of Function ◽  
Missense Variants

AbstractThe Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) gene encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals affected with neurological symptoms who carry damaging heterozygous variants in IRF2BPL. Five cases carrying nonsense variants in IRF2BPL resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The bioinformatics signature for IRF2BPL based on population genomics is consistent with a gene that is intolerant to variation. We show that the IRF2BPL ortholog in the fruit fly, called pits (protein interacting with Ttk69 and Sin3A), is broadly expressed including the nervous system. Complete loss of pits is lethal early in development, whereas partial knock-down with RNA interference in neurons leads to neurodegeneration, revealing requirement for this gene in proper neuronal function and maintenance. The nonsense variants in IRF2BPL identified in patients behave as severe loss-of-function alleles in this model organism, while ectopic expression of the missense variants leads to a range of phenotypes. Taken together, IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

scholarly journals Genetic variability of spelt factor gene in Triticum and Aegilops species

2020 ◽  
Vol 20 (S1) ◽  
Author(s):  
Valeriya Vavilova ◽  
Irina Konopatskaia ◽  
Alexandr Blinov ◽  
Elena Ya. Kondratenko ◽  
Yuliya V. Kruchinina ◽  
...  
Keyword(s):  
Phylogenetic Relationships ◽  
Chinese Spring ◽  
Stop Codon ◽  
Aegilops Tauschii ◽  
Premature Stop Codon ◽  
Gene Sequences ◽  
D Genome ◽  
Factor Gene ◽  
Spike Shape ◽  
Wide Range

Abstract Background Threshability, rachis fragility and spike shape are critical traits for the domestication and evolution of wheat, determining the crop yield and efficiency of the harvest. Spelt factor gene Q controls a wide range of domestication-related traits in polyploid wheats, including those mentioned above. The main goal of the present study was to characterise the Q gene for uninvestigated accessions of wheats, including four endemics, and Aegilops accessions, and to analyze the species evolution based on differences in Q gene sequences. Results We have studied the spike morphology for 15 accessions of wheat species, including four endemics, namely Triticum macha, T. tibetanum, T. aestivum ssp. petropavlovskyi and T. spelta ssp. yunnanense, and 24 Aegilops accessions, which are donors of B and D genomes for polyploid wheat. The Q-5A, q-5D and q-5S genes were investigated, and a novel allele of the Q-5A gene was found in accessions of T. tibetanum (KU510 and KU515). This allele was similar to the Q allele of T. aestivum cv. Chinese Spring but had an insertion 161 bp in length within exon 5. This insertion led to a frameshift and premature stop codon formation. Thus, the T. tibetanum have spelt spikes, which is probably determined by the gene Tg, rather than Q. We determined the variability within the q-5D genes among hexaploid wheat and their D genome donor Aegilops tauschii. Moreover, we studied the accessions C21–5129, KU-2074, and K-1100 of Ae. tauschii ssp. strangulata, which could be involved in the origin of hexaploid wheats. Conclusions The variability and phylogenetic relationships of the Q gene sequences studied allowed us to clarify the relationships between species of the genus Triticum and to predict the donor of the D genome among the Ae. tauschii accessions. Ae. tauschii ssp. strangulata accessions C21–5129, KU-2074 and K-1100 are the most interesting among the analysed accessions, since their partial sequence of q-5D is identical to the q-5D of T. aestivum cv. Chinese Spring. This result indicates that the donor is Ae. tauschii ssp. strangulata but not Ae. tauschii ssp. tauschii. Our analysis allowed us to clarify the phylogenetic relationships in the genus Triticum.

scholarly journals Prevalence and Distribution of Listeria monocytogenesinlAAlleles Prone to Phase Variation andinlAAlleles with Premature Stop Codon Mutations among Human, Food, Animal, and Environmental Isolates

2015 ◽  
Vol 81 (24) ◽  
pp. 8339-8345 ◽  
Author(s):  
Clyde S. Manuel ◽  
Anna Van Stelten ◽  
Martin Wiedmann ◽  
Kendra K. Nightingale ◽  
Renato H. Orsi
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Phase Variation ◽  
Virulence Gene ◽  
Farm Animals ◽  
Nucleotide Substitutions ◽  
Content Type ◽  
Niche Adaptation ◽  
Frameshift Deletion ◽  
Animal Isolates

ABSTRACTInListeria monocytogenes, 18 mutations leading to premature stop codons (PMSCs) in the virulence geneinlAhave been identified to date. While most of these mutations represent nucleotide substitutions, a frameshift deletion in a 5′ seven-adenine homopolymeric tract (HT) ininlAhas also been reported. This HT may play a role in phase variation and was first identified amongL. monocytogeneslineage II ribotype DUP-1039C isolates. In order to better understand the distribution of differentinlAmutations in this ribotype, a newly developed multiplex real-time PCR assay was used to screen 368 DUP-1039C isolates from human, animal, and food-associated sources for three known 5′inlAHT alleles: (i) wild-type (WT) (A7), (ii) frameshift (FS) (A6), and (iii) guanine interruption (A2GA4) alleles. Additionally, 228 DUP-1039C isolates were screened for allinlAPMSCs; data on the presence of allinlAPMSCs for the other 140 isolates were obtained from previous studies. The statistical analysis based on 191 epidemiologically unrelated strains showed that strains withinlAPMSC mutations (n= 41) were overrepresented among food-associated isolates, while strains encoding full-length InlA (n= 150) were overrepresented among isolates from farm animals and their environments. Furthermore, the A6allele was overrepresented and the A7allele was underrepresented among food isolates, while the A6allele was underrepresented among farm and animal isolates. Our results indicate that genetic variation ininlAcontributes to niche adaptation within the lineage II subtype DUP-1039C.

scholarly journals Synergistic Activation of Defense Responses in Arabidopsis by Simultaneous Loss of the GSL5 Callose Synthase and the EDR1 Protein Kinase

2010 ◽  
Vol 23 (5) ◽  
pp. 578-584 ◽  
Author(s):  
Anna Wawrzynska ◽  
Natalie L. Rodibaugh ◽  
Roger W. Innes
Keyword(s):  
Powdery Mildew ◽  
Positional Cloning ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Defense Responses ◽  
Loss Of Function ◽  
Callose Synthase ◽  
Synergistic Activation ◽  
Golovinomyces Cichoracearum ◽  
Inducible Gene

Loss-of-function mutations in the EDR1 gene of Arabidopsis confer enhanced resistance to Golovinomyces cichoracearum (powdery mildew). Disease resistance mediated by the edr1 mutation is dependent on an intact salicylic acid (SA) signaling pathway, but edr1 mutant plants do not constitutively express the SA-inducible gene PR-1 and are not dwarfed. To identify other components of the EDR1 signaling network, we screened for mutations that enhanced the edr1 mutant phenotype. Here, we describe an enhancer of edr1 mutant, eed3, which forms spontaneous lesions in the absence of pathogen infection, constitutively expresses both SA- and methyl jasmonate (JA)–inducible defense genes, and is dwarfed. Positional cloning of eed3 revealed that the mutation causes a premature stop codon in GLUCAN SYNTHASE-LIKE 5 (GSL5, also known as POWDERY MILDEW RESISTANT 4), which encodes a callose synthase required for pathogen-induced callose production. Significantly, gsl5 single mutants do not constitutively express PR-1 or AtERF1 (a JA-inducible gene) and are not dwarfed. Thus, loss of both EDR1 and GSL5 function has a synergistic effect. Our data suggest that EDR1 and GSL5 negatively regulate SA and JA production or signaling by independent mechanisms and that negative regulation of defense signaling by GSL5 may be independent of callose production.

scholarly journals Molecular genetic study in two patients with congenital hypoaldosteronism (types I and II) in relation to previously published hormonal studies

1998 ◽  
pp. 96-100 ◽  
Author(s):  
M Peter ◽  
K Bunger ◽  
SL Drop ◽  
WG Sippell
Keyword(s):  
Genetic Study ◽  
Stop Codon ◽  
Molecular Genetic ◽  
Premature Stop Codon ◽  
Type I ◽  
Type Ii ◽  
Loss Of Function ◽  
Molecular Genetic Study ◽  
Base Exchange ◽  
Deficiency Type

We performed a molecular genetic study in two patients with congenital hypoaldosteronism. An original study of these patients was published in this Journal in 1982. Both index cases, a girl (patient 1) and a boy (patient 2). presented with salt-wasting and failure to thrive in the neonatal period. Parents of patient 1 were not related, whereas the parents of patient 2 were cousins. Endocrine studies had shown a defect in 18-oxidation of 18-OH-corticosterone in patient 1 and a defect in the 18-hydroxylation of corticosterone in patient 2. Plasma aldosterone was decreased in both patients, whereas 18-OH-corticosterone was elevated in patient 1 and decreased in patient 2. Plasma corticosterone and 11-deoxycorticosterone were elevated in both patients, whereas cortisol and its precursors were in the normal range. According to the nomenclature proposed by Ulick, the defects are termed corticosterone methyl oxidase (CMO) deficiency type II in patient 1, and type I in patient 2 respectively. Genetic defects in the gene CYP11B2 encoding aldosterone synthase have been described in a few cases. In patient 1, we identified only one heterozygous amino acid substitution (V386A) in exon 7, which has no deleterious effect on the enzyme activity. In patient 2 and his older brother, we identified a homozygous single base exchange (G to T) in codon 255 (GAG), causing a premature stop codon E255X (TAG). The mutant enzyme has lost the five terminal exons containing the haem binding site, and is thus a loss of function enzyme. This is only the second report of a patient with CMO deficiency type II without a mutation in the exons and exon-intron boundaries, whereas the biochemical phenotype of the two brothers with CMO deficiency type I can be explained by the patient's genotype.

scholarly journals Therapeutic base and prime editing of COL7A1 mutations in recessive dystrophic epidermolysis bullosa

2021 ◽  
Author(s):  
Sung-ah Hong ◽  
Song-Ee Kim ◽  
A-young Lee ◽  
Gue-ho Hwang ◽  
Jong Hoon Kim ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Ex Vivo ◽  
Stop Codon ◽  
Point Mutations ◽  
Premature Stop Codon ◽  
Loss Of Function ◽  
Dystrophic Epidermolysis Bullosa ◽  
Immunodeficient Mice ◽  
Type Vii Collagen ◽  
Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by loss-of-function mutations in the COL7A1 gene, which encodes type VII collagen (C7), a protein that functions in skin adherence. From 36 Korean RDEB patients, we identified a total of 69 pathogenic mutations (40 variants without recurrence), including point mutations (72.5%) and insertion/deletion mutations (27.5%). We used base and prime editing to correct mutations in fibroblasts from two patients (Pat1, who carried a c.3631C>T mutation in one allele, and Pat2, who carried a c.2005C>T mutation in one allele). We applied adenine base editors (ABEs) to correct the pathogenic mutation or to bypass a premature stop codon in Pat1-derived primary fibroblasts. To expand the targeting scope, we also utilized prime editors (PEs) to correct the mutations in Pat1- and Pat2-derived fibroblasts. Ultimately, we found that both ABE- and PE-mediated correction of COL7A1 mutations restored full-length C7 expression, reversed the impaired adhesion and proliferation exhibited by the patient-derived fibroblasts, and, following transfer of edited patient-derived fibroblasts into the skin of immunodeficient mice, led to C7 deposition within the dermal-epidermal junction. These results suggest that base and prime editing could be feasible strategies for ex vivo gene editing to treat RDEB.

scholarly journals Sequencing Analysis and Enzyme Activity Assay of SrUGT76G1 Revealed the Mechanism Toward on/off Production of Rebaudioside-A in Stevia Plants

2021 ◽  
Author(s):  
Simone Ribeiro Lucho ◽  
Marcelo do Amaral ◽  
Valmor Bianchi ◽  
Lorena Almagro ◽  
Maria Ferrer ◽  
...  
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Binding Pocket ◽  
Structural Features ◽  
Steviol Glycosides ◽  
Sequencing Analysis ◽  
Structural Level ◽  
Rebaudioside A ◽  
Enzyme Activity Assay ◽  
Structure Activity

Abstract Stevia plants is known for its ability to synthesize steviol glycosides (SGs), a natural sweetener blend. Stevioside (STEV) and Rebaudioside-A (Reb-A) are the main SGs. However, Reb-A is more palatable than STEV and shows reduced bitter aftertaste. SrUGT76G1 catalyzes the conversion of STEV to Reb-A, improving their organoleptic properties. The better understanding of the structure/activity of SrUGT76G1 would allow shedding light up on on/off production of Reb-A in stevia plants. Thus, we analyzed the STEV and Reb-A content in stevia leaves of plants from Brazil and Spain and did not find detectable levels of Reb-A in Brazilian samples (off production). For this reason, we used a sequencing tool to study at the genetic and structural level the SrUGT76G1 gene. Changes in key amino acid residues in Brazilian samples were found, such as Leu204Phe, Thr284Leu and Leu126Ile. Leu204Phe mutants can narrow substrate-binding pocket to favor flavonoids recognition and decrease SGs synthesis, while Thr284 is considered key for 1,3-glucosylation of SGs, including Reb-A. These punctual mutations may partly explain the lack of functionality of UGT76G1 enzyme and off production of Reb-A in stevia plants from Brazil. Following this trend, Brazilian samples exhibited a T-to-A substitution, resulting in premature stop codon. As expected, the relative expression of SrUGT76G1 gene showed a higher level in Spanish samples than in Brazilian ones. Collectively, the results presented here show the structure-activity interplay of SrUGT76G1 enzyme and provide new insights on structural features and its role toward Reb-A synthesis.

scholarly journals A P3A-Type ATPase and an R2R3-MYB Transcription Factor Are Involved in Vacuolar Acidification and Flower Coloration in Soybean

2020 ◽  
Vol 11 ◽  
Author(s):  
Jagadeesh Sundaramoorthy ◽  
Gyu Tae Park ◽  
Jeong-Dong Lee ◽  
Jeong Hoe Kim ◽  
Hak Soo Seo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Anthocyanin Biosynthesis ◽  
Stop Codon ◽  
Binding Capacity ◽  
Premature Stop Codon ◽  
Flower Color ◽  
Myb Transcription Factor ◽  
Nucleotide Substitutions ◽  
Vacuolar Acidification ◽  
Vacuolar Ph

The determination of flower color mainly depends on the anthocyanin biosynthesis pathway and vacuolar pH; however, unlike the former, the mechanism of vacuolar acidification in soybean remains uncharacterized at the molecular level. To investigate this mechanism, we isolated four recessive purple–blue EMS-induced flower mutants from the purple flower soybean cultivar, Pungsannamul. The petals of all the mutants had increased pH compared with those of wild Pungsannamul. One of the mutants had a single nucleotide substitution in GmPH4, a regulator gene encoding an MYB transcription factor, and the substitution resulted in a premature stop codon in its first exon. The other three mutants had nucleotide substitutions in GmPH5, a single new gene that we identified by physical mapping. It corresponds to Glyma.03G262600 in chromosome 3 and encodes a proton pump that belongs to the P3A-ATPase family. The substitutions resulted in a premature stop codon, which may be a defect in the ATP-binding capacity of GmPH5 and possibly a catalytic inefficiency of GmPH5. The result is consistent with their genetic recessiveness as well as the high pH of mutant petals, suggesting that GmPH5 is directly involved in vacuolar acidification. We also found that the expression of GmPH5 and several putative “acidifying” genes in the gmph4 mutant was remarkably reduced, indicating that GmPH4 may regulate the genes involved in determining the vacuolar pH of soybean petals.

Sign in / Sign up

Export Citation Format

Share Document