scholarly journals Loss of Function of OsARG Resulted in Pepper-Shaped Husk in Indica Rice

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 523
Author(s):  
Yan Zheng ◽  
Mjomba Fredrick Mwamburi ◽  
Huaqing Liu ◽  
Feng Wang
Keyword(s):  
Complex Traits ◽  
Target Gene ◽  
Indica Rice ◽  
Recessive Gene ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Regenerated Plants ◽  
Grain Width ◽  
Different Genetic Background ◽  
Mutant Phenotypes

Grain shape is one of the most important and complex traits determining the grain yield in rice. In this study, we discovered two rice mutants with defective shape spikelets, designated as psh1-1/2 (pepper-shaped husk 1-1/2), which were both isolated from the tissue-culture-regenerated plants of indica cultivar Minghui 86. The two mutants showed the same mutant phenotypes, containing pepper-shaped spikelets; shorter, smaller and compact panicles; very low seed-setting rate; high percentage of split grains; and lower grain width. Genetic analysis indicated that the mutant phenotypes were controlled by a recessive gene. Gene mapping indicated that the target gene PSH1 was located on the short arm of chromosome 4. Sequencing analysis revealed that the two mutants each had a different nonsense mutation in OsARG, confirming that the target gene is OsARG. Compared with the previously reported OsARG mutant nglf-1, psh1-1/2 possessed some distinct mutant phenotypes, probably because of the influence of different genetic background, suggesting that OsARG may function differently under different genetic backgrounds.

scholarly journals Disease heritability enrichment of regulatory elements is concentrated in elements with ancient sequence age and conserved function across species

2018 ◽  
Author(s):  
Margaux L.A. Hujoel ◽  
Steven Gazal ◽  
Farhad Hormozdiari ◽  
Bryce van de Geijn ◽  
Alkes L. Price
Keyword(s):  
Complex Traits ◽  
Negative Selection ◽  
Target Gene ◽  
Regulatory Element ◽  
Complex Trait ◽  
Regulatory Elements ◽  
Mean Value ◽  
Regulatory Function ◽  
Loss Of Function ◽  
The Mean

AbstractRegulatory elements, e.g. enhancers and promoters, have been widely reported to be enriched for disease and complex trait heritability. We investigated how this enrichment varies with the age of the underlying genome sequence, the conservation of regulatory function across species, and the target gene of the regulatory element. We estimated heritability enrichment by applying stratified LD score regression to summary statistics from 41 independent diseases and complex traits (average N =320K) and meta-analyzing results across traits. Enrichment of human enhancers and promoters was larger in elements with older sequence age, assessed via alignment with other species irrespective of conserved functionality: enhancer elements with ancient sequence age (older than the split between marsupial and placental mammals) were 8.8x enriched (vs. 2.5x for all enhancers; p = 3e-14), and promoter elements with ancient sequence age were 13.5x enriched (vs. 5.1x for all promoters; p = 5e-16). Enrichment of human enhancers and promoters was also larger in elements whose regulatory function was conserved across species, e.g. human enhancers that were enhancers in ≥5 of 9 other mammals were 4.6x enriched (p = 5e-12 vs. all enhancers). Enrichment of human promoters was larger in promoters of loss-of-function intolerant genes: 12.0x enrichment (p = 8e-15 vs. all promoters). The mean value of several measures of negative selection within these genomic annotations mirrored all of these findings. Notably, the annotations with these excess heritability enrichments were jointly significant conditional on each other and on our baseline-LD model, which includes a broad set of coding, conserved, regulatory and LD-related annotations.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

scholarly journals Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 643-655 ◽  
Author(s):  
Bruno van Swinderen ◽  
Laura B Metz ◽  
Laynie D Shebester ◽  
Jane E Mendel ◽  
Paul W Sternberg ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Novel Mutation ◽  
Volatile Anesthetic ◽  
Loss Of Function ◽  
Wild Type ◽  
Α Subunit ◽  
C Elegans ◽  
Missense Mutant ◽  
Anesthetic Action ◽  
Mutant Phenotypes

Abstract To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the α-subunit of Go, have EC50s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goα, and presynaptic Goα-effectors are candidate VA molecular targets.

scholarly journals A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Sonal Nagarkar-Jaiswal ◽  
Pei-Tseng Lee ◽  
Megan E Campbell ◽  
Kuchuan Chen ◽  
Stephanie Anguiano-Zarate ◽  
...  
Keyword(s):  
Null Mutant ◽  
Loss Of Function ◽  
Severe Loss ◽  
New Strategy ◽  
Mutant Phenotypes

Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates.

scholarly journals Whole-Exome Sequencing Analysis of Human Semen Quality in Russian Multiethnic Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Semyon Kolmykov ◽  
Gennady Vasiliev ◽  
Ludmila Osadchuk ◽  
Maxim Kleschev ◽  
Alexander Osadchuk
Keyword(s):  
Exome Sequencing ◽  
Ethnic Groups ◽  
Whole Exome Sequencing ◽  
Complex Traits ◽  
Semen Quality ◽  
Population Sample ◽  
Sperm Concentration ◽  
Sequencing Analysis ◽  
New Genes ◽  
Whole Exome

The global trend toward the reduction of human spermatogenic function observed in many countries, including Russia, raised the problem of extensive screening and monitoring of male fertility and elucidation of its genetic and ethnic mechanisms. Recently, whole-exome sequencing (WES) was developed as a powerful tool for genetic analysis of complex traits. We present here the first Russian WES study for identification of new genes associated with semen quality. The experimental 3 × 2 design of the WES study was based on the analysis of 157 samples including three ethnic groups—Slavs (59), Buryats (n = 49), and Yakuts (n = 49), and two different semen quality groups—pathozoospermia (n = 95) and normospermia (n = 62). Additionally, our WES study group was negative for complete AZF microdeletions of the Y-chromosome. The normospermia group included men with normal sperm parameters in accordance with the WHO-recommended reference limit. The pathozoospermia group included men with impaired semen quality, namely, with any combined parameters of sperm concentration <15 × 106/ml, and/or progressive motility <32%, and/or normal morphology <4%. The WES was performed for all 157 samples. Subsequent calling and filtering of variants were carried out according to the GATK Best Practices recommendations. On the genotyping stage, the samples were combined into four cohorts: three sets corresponded to three ethnic groups, and the fourth set contained all the 157 whole-exome samples. Association of the obtained polymorphisms with semen quality parameters was investigated using the χ2 test. To prioritize the obtained variants associated with pathozoospermia, their effects were determined using Ensembl Variant Effect Predictor. Moreover, polymorphisms located in genes expressed in the testis were revealed based on the genomic annotation. As a result, the nine potential SNP markers rs6971091, rs557806, rs610308, rs556052, rs1289658, rs278981, rs1129172, rs12268007, and rs17228441 were selected for subsequent verification on our previously collected population sample (about 1,500 males). The selected variants located in seven genes FAM71F1, PPP1R15A, TRIM45, PRAME, RBM47, WDFY4, and FSIP2 that are expressed in the testis and play an important role in cell proliferation, meiosis, and apoptosis.

Knockdown of long noncoding RNA AC245100.4 inhibits the tumorigenesis of prostate cancer cells via the STAT3/NR4A3 axis

Epigenomics ◽  
2021 ◽  
Author(s):  
Chi Liu ◽  
Ping Lin ◽  
Jiabin Zhao ◽  
Hui Xie ◽  
Rou Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Rna Sequencing ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Transcriptional Repressor ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Prostate Cancer Cells ◽  
Rna Immunoprecipitation

Aim: To explore the role and mechanism of long noncoding RNA AC245100.4 and NR4A3 in prostate cancer (PCa). Methods: RNA-sequencing analysis was used to detect the downstream genes of AC245100.4. A series of gain- and loss-of-function approaches were used to investigate the roles of AC245100.4 and NR4A3. RNA immunoprecipitation was performed to examine the interaction between AC245100.4 and STAT3. Results: AC245100.4 was significantly upregulated in PCa cells and tissues. Knockdown of AC21500.4 significantly inhibited the tumorigenesis of PCa cells. Mechanistically, AC245100.4 deregulated the transcription of NR4A3 via increasing p-STAT3, which acted as a transcriptional repressor of NR4A3. Conclusion: Knockdown of lncRNA AC245100.4 inhibits the tumorigenesis of PCa cells via the STAT3/ NR4A3 axis.

Cytological characterisation of the mutant phenotypes produced during early embryogenesis by null and loss-of-function alleles of the gammaTub37C gene in Drosophila

1999 ◽  
Vol 112 (5) ◽  
pp. 659-667 ◽  
Author(s):  
S. Llamazares ◽  
G. Tavosanis ◽  
C. Gonzalez
Keyword(s):  
Polar Body ◽  
Nuclear Proliferation ◽  
Early Embryogenesis ◽  
Drosophila Embryo ◽  
Loss Of Function ◽  
Female Meiosis ◽  
Polar Bodies ◽  
Early Drosophila Embryo ◽  
Gamma Tubulin ◽  
Mutant Phenotypes

We have studied the mutant phenotypes brought about during early embryogenesis by mutation in the gammaTub37C gene, one of the two isoforms of gamma-tubulin that have been identified in Drosophila. We have focused our attention on fs(2)TW1(1) and fs(2)TW1(RU34), a null and a hypomorph allele of this gene, whose sequences we report in this work. We have found that the abnormal meiotic figures observed in mutant stage 14 oocytes are not observed in laid oocytes or fertilised embryos, suggesting that these abnormal meiotic figures are not terminally arrested. We have also concluded that both null and hypomorph alleles lead to a total arrest of nuclear proliferation during early embryogenesis. This is in contrast to their effect on female meiosis-I where hypomorph alleles display a much weaker phenotype. Finally, we have observed that null and hypomorph alleles lead to some distinct phenotypes. Unfertilised laid oocytes and fertilised embryos deficient for gammaTub37C do not contain polar bodies and have a few bipolar microtubule arrays. In contrast, oocytes and embryos from weaker alleles do not have these microtubule arrays, but do contain polar bodies, or polar-body-like structures. These results indicate that gammaTub37C is essential for nuclear proliferation in the early Drosophila embryo.

Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 231-240 ◽  
Author(s):  
E.J. Lambie ◽  
J. Kimble
Keyword(s):  
Gene Expression ◽  
Double Mutant ◽  
Transmembrane Proteins ◽  
Cell Interactions ◽  
Loss Of Function ◽  
Cell Fates ◽  
Single Mutant ◽  
C Elegans ◽  
Homologous Genes ◽  
Mutant Phenotypes

Two homologous genes, lin-12 and glp-1, encode transmembrane proteins required for regulatory cell interactions during C. elegans development. Based on their single mutant phenotypes, each gene has been thought to govern a distinct set of cell fates. We show here that lin-12 and glp-1 are functionally redundant during embryogenesis: Unlike either single mutant, the lin-12 glp-1 double mutant dies soon after hatching. Numerous cellular defects can be observed in these Lag (for lin-12 and glp-1) double mutants. Furthermore, we have identified two genes, lag-1 and lag-2, that appear to be required for both lin-12 and glp-1-mediated cell interactions. Strong loss-of-function lag mutants are phenotypically indistinguishable from the lin-12 glp-1 double; weak lag mutants have phenotypes typical of lin-12 and glp-1 single mutants. We speculate that the lin-12 and glp-1 proteins are biochemically interchangeable and that their divergent roles in development may rely largely on differences in gene expression.

scholarly journals miR-34a-5p Increases Hepatic Triglycerides and Total Cholesterol Levels by Regulating ACSL1 Protein Expression in Laying Hens

2019 ◽  
Vol 20 (18) ◽  
pp. 4420 ◽  
Author(s):  
Wei-Hua Tian ◽  
Zhang Wang ◽  
Ya-Xin Yue ◽  
Hong Li ◽  
Zhuan-Jian Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Total Cholesterol ◽  
Lipid Content ◽  
Target Gene ◽  
Laying Hens ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Regulatory Molecule ◽  
Cholesterol Levels ◽  
Chain Acyl

Accumulating evidence has shown that miR-34a serves as a posttranscriptional regulatory molecule of lipid metabolism in mammals. However, little studies about miR-34a on lipid metabolism in poultry have been reported until now. To gain insight into the biological functions and action mechanisms of miR-34a on hepatic lipid metabolism in poultry, we firstly investigated the expression pattern of miR-34a-5p, a member of miR-34a family, in liver of chicken, and determined its function in hepatocyte lipid metabolism by miR-34a-5p overexpression and inhibition, respectively. We then validated the interaction between miR-34a-5p and its target using dual-luciferase reporter assay, and explored the action mechanism of miR-34a-5p on its target by qPCR and Western blotting. Additionally, we looked into the function of the target gene on hepatocyte lipid metabolism by gain- and loss-of-function experiments. Our results indicated that miR-34a-5p showed a significantly higher expression level in livers in peak-laying hens than that in pre-laying hens. miR-34a-5p could increase the intracellular levels of triglycerides and total cholesterol in hepatocyte. Furthermore, miR-34a-5p functioned by inhibiting the translation of its target gene, long-chain acyl-CoA synthetase 1 (ACSL1), which negatively regulates hepatocyte lipid content. In conclusion, miR-34a-5p could increase intracellular lipid content by reducing the protein level, without influencing mRNA stability of the ACSL1 gene in chickens.

Fine mapping and candidate gene analysis of LM3, a novel lesion mimic gene in rice

Biologia ◽  
2013 ◽  
Vol 68 (1) ◽  
Author(s):  
Yuxiang Zeng ◽  
Liangyong Ma ◽  
Zhijuan Ji ◽  
Zhihua Wen ◽  
Ximing Li ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Target Gene ◽  
Recessive Gene ◽  
Coding Region ◽  
Uroporphyrinogen Decarboxylase ◽  
Single Nucleotide ◽  
Lesion Mimic ◽  
Indel Markers ◽  
Fourth Exon ◽  
Simple Sequence

AbstractA rice lesion mimic mutant, lm3, was obtained by the mutagenesis of an indica cultivar, 93-11, using γ-ray radiation. Brownish lesions appeared on the leaves of lm3 at the young seedling stage and persisted until the ripening stage. The lm3 mutant was characterised by a shorter plant height and delayed heading compared with the wild-type 93-11. A genetic analysis indicated that the lesion mimic phenotype was controlled by a single recessive gene. Using simple sequence repeat (SSR) markers, the target gene LM3 was first located between marker RM5748 and RM14906 on chromosome 3. We then developed Insertion-Deletion (InDel) markers to fine-map LM3, and the locus was localised to a 29 kb region defined by two InDel markers, In12571 and In12600. Five ORFs were predicted in the candidate region, and DNA sequencing detected a single-nucleotide polymorphism (SNP) in the coding region of LOC Os03g21900. The SNP in the fourth exon (C in 93-11; T in lm3) of LOC_Os03g21900 results in the substitution of a proline (P) with a serine (S) at the 140th amino acid of the deduced uroporphyrinogen decarboxylase protein. We did not detect polymorphisms in the other predicted ORF regions between lm3 and 93-11. These results suggest that LOC_Os03g21900 is the most likely candidate gene for LM3.

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