Barley Ant17, encoding flavanone 3-hydroxylase (F3H), is a promising target locus for attaining anthocyanin/proanthocyanidin-free plants without pleiotropic reduction of grain dormancy

Genome ◽  
2015 ◽  
Vol 58 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Eiko Himi ◽  
Shin Taketa
Keyword(s):  
Crop Production ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Preharvest Sprouting ◽  
Economic Losses ◽  
Recessive Mutations ◽  
Grain Dormancy ◽  
Target Locus ◽  
Promising Target ◽  
Sprouting Resistance

Preharvest sprouting is a serious problem in grain crop production because it causes quality deterioration and economic losses. It is well known that grain colour is closely associated with grain dormancy in wheat; white-grained lines without accumulating proanthocyanidins in testa tend to be more susceptible to preharvest sprouting than red ones. All available white-grained wheat lines are restricted to triple recessive mutations at the R loci (R-A1, R-B1, and R-D1), but barley is known to have 11 independent loci conferring the proanthocyanidin-free grain phenotype. In this study, we evaluated the dormancy levels of anthocyanin/proanthocyanidin-free ant17 mutants. Three ant17 mutants showed the same levels of dormancy as their respective wild types. Sequencing of three independent ant17 alleles detected a point mutation within the coding regions of flavanone-3-hydroxylase (F3H), which are predicted to cause a premature stop codon at different sites. The F3H locus completely cosegregated with the Ant17 position on the chromosome arm 2HL. Expression of the barley F3H gene was observed in pigmented tissues, but not in nonpigmented roots and stems. This result indicates that wheat F3H may be a promising new target locus for breeding white-grained lines with a practical level of preharvest sprouting resistance.

Mapping quantitative trait loci associated with variation in grain dormancy in Australian wheat

2001 ◽  
Vol 52 (12) ◽  
pp. 1257 ◽  
Author(s):  
D. J. Mares ◽  
K. Mrva
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Preharvest Sprouting ◽  
Germination Index ◽  
Economic Losses ◽  
Doubled Haploid Population ◽  
Grain Dormancy ◽  
Grain Handling ◽  
Trait Loci ◽  
Haploid Population

Preharvest sprouting is a problem in many regions of the world, resulting in downgrading of quality, substantial economic losses to wheat growers, and difficulties for grain handling and marketing agencies. Improvements in tolerance from the introduction of better grain dormancy at, or near, harvest-ripeness would be expected to have a significant impact on the incidence and severity of sprouting. Intermediate levels of dormancy in older Australian wheats, such as Halberd, and a small number of current cultivars could be used in the short term while more extreme dormancy is being introgressed into locally adapted germplasm. A doubled haploid population derived from Cranbrook (extremely non-dormant, very susceptible to sprouting) x Halberd (intermediate dormancy, moderately tolerant to preharvest sprouting) was grown in replicated experiments and ripe grain harvested for assessment of dormancy, measured as a germination index. Consistent differences were observed between the parents in both experiments. For the bulk of the progeny, the germination index fell within a range defined by Cranbrook at the upper and Halberd at the lower end. Significant quantitative trait loci, all contributed by the very susceptible parent, that explained 11%, 9%, and 9% of the phenotypic variation were identified on chromosome arms 2AL, 2DL, and 4AL, respectively. These QTLs offer the opportunity to develop molecular markers for grain dormancy and to develop a better understanding of the mechanisms involved in this trait.

Ectopic Transcript Analysis Indicates that Allelic Exclusion is an Important Cause of Type I Protein C Deficiency in Patients with Nonsense and Frameshift Mutations in the PROC Gene

1996 ◽  
Vol 75 (06) ◽  
pp. 870-876 ◽  
Author(s):  
José Manuel Soria ◽  
Lutz-Peter Berg ◽  
Jordi Fontcuberta ◽  
Vijay V Kakkar ◽  
Xavier Estivill ◽  
...  
Keyword(s):  
Splice Site ◽  
Protein C ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Allelic Exclusion ◽  
Polymorphism Analysis ◽  
Type I ◽  
Protein C Deficiency ◽  
Nonsense Mutations ◽  
Stop Codons

SummaryNonsense mutations, deletions and splice site mutations are a common cause of type I protein C deficiency. Either directly or indirectly by altering the reading frame, these' lesions generate or may generate premature stop codons and could therefore be expected to result in premature termination of translation. In this study, the possibility that such mutations could instead exert their pathological effects at an earlier stage in the expression pathway, through “allelic exclusion” at the RNA level, was investigated. Protein C (PROC) mRNA was analysed in seven Spanish type I protein C deficient patients heterozygous for two nonsense mutations, a 7bp deletion, a 2bp insertion and three splice site mutations. Ectopic RNA transcripts from patient and control lymphocytes were analysed by RT-PCR and direct sequencing of amplified PROC cDNA fragments. The nonsense mutations and the deletion were absent from the cDNAs indicating that only mRNA derived from the normal allele had been expressed. Similarly for the splice site mutations, only normal PROC cDNAs were obtained. In one case, exclusion of the mutated allele could be confirmed by polymorphism analysis. In contrast to these six mutations, the 2 bp insertion was not associated with loss of mRNA from the mutated allele. In this case, cDNA analysis revealed the absence of 19 bases from the PROC mRNA consistent with the generation and utilization of a cryptic splice site 3’ to the site of mutation, which would result in a frameshift and a premature stop codon. It is concluded that allelic exclusion is a common causative mechanism in those cases of type I protein C deficiency which result from mutations that introduce premature stop codons

Exploring Molecular Markers of Preharvest Sprouting Resistance Gene Using Wheat Intact Spikes by Association Analysis

2014 ◽  
Vol 40 (10) ◽  
pp. 1725 ◽  
Author(s):  
Yu-Lei ZHU ◽  
Sheng-Xing WANG ◽  
Liang-Xia ZHAO ◽  
De-Xin ZHANG ◽  
Jian-Bang HU ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Resistance Gene ◽  
Association Analysis ◽  
Preharvest Sprouting ◽  
Sprouting Resistance ◽  
Preharvest Sprouting Resistance

Induction of Translational Readthrough across the Thalassemia-Causing Premature Stop Codon in β-Globin-Encoding mRNA

Biochemistry ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Debaleena Kar ◽  
Karthi Sellamuthu ◽  
Sangeetha Devi Kumar ◽  
Sandeep M. Eswarappa
Keyword(s):  
Stop Codon ◽  
Premature Stop Codon ◽  
Translational Readthrough

scholarly journals A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 411
Author(s):  
María Lachgar ◽  
Matías Morín ◽  
Manuela Villamar ◽  
Ignacio del Castillo ◽  
Miguel Ángel Moreno-Pelayo
Keyword(s):  
Hearing Loss ◽  
Stop Codon ◽  
Coiled Coil ◽  
Premature Stop Codon ◽  
Scaffolding Protein ◽  
Common Mechanism ◽  
Chinese Family ◽  
Truncating Mutation ◽  
Spanish Family ◽  
Sensory Defect

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c.832_836delCCTCA) identified in a Spanish family by using a custom NGS targeted gene panel (OTO-NGS-v2). This frameshift mutation produces a premature stop codon that may lead in the absence of NMD to a shorter variant (p.Pro278Alafs*10) that truncates HOMER2 at the CDC42 binding domain (CBD) of the coiled-coil structure, a region that is essential for protein multimerization and HOMER2-CDC42 interaction. c.832_836delCCTCA mutation is placed close to the previously identified c.840_840dup mutation found in a Chinese family that truncates the protein (p.Met281Hisfs*9) at the CBD. Functional assessment of the Chinese mutant revealed decreased protein stability, reduced ability to multimerize, and altered distribution pattern in transfected cells when compared with wild-type HOMER2. Interestingly, the Spanish and Chinese frameshift mutations might exert a similar effect at the protein level, leading to truncated mutants with the same Ct aberrant protein tail, thus suggesting that they can share a common mechanism of pathogenesis. Indeed, age-matched patients in both families display quite similar hearing loss phenotypes consisting of early-onset, moderate-to-profound progressive hearing loss. In summary, we have identified the third variant in HOMER2, which is the first one identified in the Spanish population, thus contributing to expanding the mutational spectrum of this gene in other populations, and also to clarifying the genotype–phenotype correlations of DFNA68 hearing loss.

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 A rare large duplication of MLH1 identified in Lynch syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Nagarajan Paramasivam ◽  
Obul Reddy Bandapalli ◽  
Matthias Schlesner ◽  
Tianhui Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lynch Syndrome ◽  
Splice Site ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Splice Donor Site ◽  
Laboratory Diagnostics ◽  
Mmr Genes ◽  
Base Pair Deletion ◽  
Splice Site Variant

Abstract Background The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. Methods In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. Results Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. Conclusions We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

2013 ◽  
Vol 62 (12) ◽  
pp. 1799-1806 ◽  
Author(s):  
Anne Holch ◽  
Hanne Ingmer ◽  
Tine Rask Licht ◽  
Lone Gram
Keyword(s):  
Listeria Monocytogenes ◽  
Guinea Pig ◽  
Food Processing ◽  
Guinea Pigs ◽  
Stop Codon ◽  
Fetal Liver ◽  
Fatal Case ◽  
Premature Stop Codon ◽  
Tissue Samples ◽  
Pregnant Mice

Listeria monocytogenes is an important food-borne bacterial pathogen and listeriosis can result in abortions in pregnant women. The bacterium can colonize food-processing environments, where specific molecular subtypes can persist for years. The purpose of this study was to determine the virulence potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10 % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlA m* (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas the maternofetal control was found in 6 % of fetal tissue samples. As the food-processing persistent strains carry a premature stop codon in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we hypothesize that listerial crossing of the placental barrier can occur by a mechanism that is independent of an interaction between E-cadherin and InlA.

Sign in / Sign up

Export Citation Format

Share Document