scholarly journals Natural Variants of ELF3 Affect Thermomorphogenesis by Transcriptionally Modulating PIF4-Dependent Auxin Response Genes

2015 ◽  
Author(s):  
Anja Raschke ◽  
Carla Ibañez ◽  
Kristian Karsten Ullrich ◽  
Muhammad Usman Anwer ◽  
Sebastian Becker ◽  
...  
Keyword(s):  
Ambient Temperature ◽  
Quantitative Trait ◽  
Natural Variation ◽  
Target Genes ◽  
Allelic Variation ◽  
Selective Advantage ◽  
Coding Region ◽  
Temperature Changes ◽  
Natural Variants ◽  
Trait Locus

Perception and transduction of temperature changes result in altered growth enabling plants to adapt to increased ambient temperature. While PHYTOCHROME-INTERACTING FACTOR4 (PIF4) has been identified as a major ambient temperature signaling hub, its upstream regulation seems complex and is poorly understood. Here, we exploited natural variation for thermo-responsive growth in Arabidopsis thaliana using quantitative trait locus (QTL) analysis. We identified GIRAFFE2.1, a major QTL explaining ~18% of the phenotypic variation for temperature-induced hypocotyl elongation in the Bay-0 x Sha recombinant inbred line population. Transgenic complementation demonstrated that allelic variation in the circadian clock regulator EARLY FLOWERING3 (ELF3) is underlying this QTL. The source of variation could be allocated to a single nucleotide polymorphism in the ELF3 coding region, resulting in differential expression of PIF4 and its target genes, likely causing the observed natural variation in thermo-responsive growth. In combination with other recent studies, this work establishes the role of ELF3 in the ambient temperature signaling network. Natural variation of ELF3-mediated gating of PIF4 expression during nightly growing periods seems to be affected by a coding sequence quantitative trait nucleotide that confers a selective advantage in certain environments. In addition, natural ELF3 alleles seem to differentially integrate temperature and photoperiod cues to induce architectural changes. Thus, ELF3 emerges as an essential coordinator of growth and development in response to diverse environmental cues and implicates ELF3 as an important target of adaptation.

scholarly journals Genetic and Molecular Analysis of smooth, a Quantitative Trait Locus Affecting Bristle Number in Drosophila melanogaster

Genetics ◽  
1997 ◽  
Vol 146 (2) ◽  
pp. 607-618
Author(s):  
Petra zur Lage ◽  
Antony D Shrimpton ◽  
Andrew J Flavell ◽  
Trudy F C Mackay ◽  
Andrew J Leigh Brown
Keyword(s):  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Allelic Variation ◽  
P Element ◽  
Selection Line ◽  
Element Insertion ◽  
Bristle Number ◽  
Trait Locus

A semi-lethal, sterile allele of the smooth locus (2-91.5), sm3, was discovered in an artificial selection line for low abdominal bristle number that had been started from a P-M dysgenic cross. The fitness effects and extremely low bristle number phenotype of the allele could not be separated by recombination from a P-element insertion at cytological location 56E, and precise excision of the P element at this site was associated with reversion to wild type. The smooth gene was cloned using the P-element insertion as a tag. The gene encodes a 2.6-kb transcript derived from 10 exons and covers a genomic region of at least 80 kb. The Drosophila smooth gene shares substantial sequence identity with a group of RNA binding proteins, with the closest relationship being to the human heterogeneous nuclear ribonucleoprotein L gene. The smooth gene is by definition an abdominal bristle number quantitative trait locus, but further work is required to discern whether naturally occurring allelic variation at this locus is a source of genetic variation for abdominal bristle number in natural populations.

scholarly journals A compendium of uniformly processed human gene expression and splicing quantitative trait loci

2021 ◽  
Vol 53 (9) ◽  
pp. 1290-1299
Author(s):  
Nurlan Kerimov ◽  
James D. Hayhurst ◽  
Kateryna Peikova ◽  
Jonathan R. Manning ◽  
Peter Walter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Target Genes ◽  
Genome Wide Association Study ◽  
Cell Types ◽  
Summary Statistics ◽  
Genome Wide ◽  
Cell Type Specific ◽  
Trait Locus ◽  
Complex Human Traits

AbstractMany gene expression quantitative trait locus (eQTL) studies have published their summary statistics, which can be used to gain insight into complex human traits by downstream analyses, such as fine mapping and co-localization. However, technical differences between these datasets are a barrier to their widespread use. Consequently, target genes for most genome-wide association study (GWAS) signals have still not been identified. In the present study, we present the eQTL Catalogue (https://www.ebi.ac.uk/eqtl), a resource of quality-controlled, uniformly re-computed gene expression and splicing QTLs from 21 studies. We find that, for matching cell types and tissues, the eQTL effect sizes are highly reproducible between studies. Although most QTLs were shared between most bulk tissues, we identified a greater diversity of cell-type-specific QTLs from purified cell types, a subset of which also manifested as new disease co-localizations. Our summary statistics are freely available to enable the systematic interpretation of human GWAS associations across many cell types and tissues.

scholarly journals Genetic and Molecular Analyses of Natural Variation Indicate CBF2 as a Candidate Gene for Underlying a Freezing Tolerance Quantitative Trait Locus in Arabidopsis

2005 ◽  
Vol 139 (3) ◽  
pp. 1304-1312 ◽  
Author(s):  
Carlos Alonso-Blanco ◽  
Concepción Gomez-Mena ◽  
Francisco Llorente ◽  
Maarten Koornneef ◽  
Julio Salinas ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Candidate Gene ◽  
Freezing Tolerance ◽  
Quantitative Trait ◽  
Natural Variation ◽  
Molecular Analyses ◽  
Trait Locus

scholarly journals DELAY OF GERMINATION 6, encoding the ANAC060 transcription factor, inhibits seed dormancy

2021 ◽  
Author(s):  
Shuang Song ◽  
Hanzi He ◽  
Kerstin Guhl ◽  
Marieke van Bolderen Veldkamp ◽  
Gonda Buijs ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Seed Dormancy ◽  
Quantitative Trait ◽  
Genomic Sequence ◽  
Class A ◽  
Natural Variants ◽  
Alternatively Spliced ◽  
Membrane Bound ◽  
Trait Locus ◽  
Pp2c Gene

The timing of seed germination is regulated by seed dormancy. There is ample natural variation for seed dormancy among as well as within plant species. In Arabidopsis several DELAY OF GERMINATION quantitative trait loci have been identified, of which DOG1 is best studied. Here we report the identification of DOG6, a quantitative trait locus with a similar strong effect on seed dormancy as DOG1. DOG6 affects the timing of germination both in laboratory as well as in field conditions. Complementation cloning revealed that DOG6 encodes the membrane bound transcription factor ANAC060. The absence of the ANAC060 protein or its sequestration outside the nucleus results in increased seed dormancy levels. The different natural variants of ANAC060 differ for the presence of the membrane binding domain, either due to the fact that this domain is absent in the genomic sequence or because the cDNA is alternatively spliced. Our data indicates that ANAC060 regulates seed dormancy by among others binding to and regulating the expression of protein phosphatases 2C class A proteins including PROTEIN PHOSPHATASE 2CA (PP2CA), ABI FIVE BINDING PROTEIN 3 (AFP3) and HIGHLY ABA-INDUCED PP2C GENE 3 (HAI3).

scholarly journals Fine Mapping and Analysis of Candidate Genes for qFT7.1, a Major Quantitative Trait Locus Controlling Flowering Time in Brassica Rapa L

2021 ◽  
Author(s):  
Gaoyang Qu ◽  
Yue Gao ◽  
Xian Wang ◽  
Wei Fu ◽  
Yunxia Sun ◽  
...  
Keyword(s):  
Quantitative Trait Locus ◽  
Flowering Time ◽  
Brassica Rapa ◽  
Quantitative Trait ◽  
Recurrent Parent ◽  
Coding Region ◽  
Late Flowering ◽  
Synonymous Mutations ◽  
Trait Locus ◽  
Delayed Flowering

Abstract In Brassica rapa, flowering time (FT) is an important agronomic trait that affects the yield, quality, and adaption. FT a complicated trait that is regulated by many genes and is affected greatly by the environment. In this study, a chromosome segment substitution line (CSSL), CSSL16, was selected that showed later flowering than the recurrent parent, rapid-cycling inbred line of B. rapa (RcBr). Using Bulked Segregant RNA sequencing, we identified a late flowering quantitative trait locus (QTL), designated as qFT7.1, on chromosome A07 based on a secondary-F2 population derived from the cross between CSSL16 and RcBr. qFT7.1 was further validated by conventional QTL mapping. This QTL explained 39.9% (logarithm of odds = 32.2) of the phenotypic variations and was fine mapped to a 56.4-kb interval using recombinant analysis. Expression analysis suggests that BraA07g018240.3C, which is homologous with ATC (encoding Arabidopsis thaliana CENTRORADIALIS homologue), a gene for delayed flowering in Arabidopsis as the most promising candidate gene. Sequence analysis demonstrated that two synonymous mutations existed in the coding region and numerous bases replacements existed in promoter region between BraA07g018240.3C from CSSL16 and RcBr. The results will increase our knowledge related to the molecular mechanism of late flowering in B. rapa, and lay a solid foundation for the breeding of late bolting in B. rapa.

scholarly journals Summary-data-based mendelian randomisation reveals druggable targets for multiple sclerosis

2020 ◽  
Author(s):  
Benjamin Meir Jacobs ◽  
Thomas Taylor ◽  
Amine Awad ◽  
David Baker ◽  
Gavin Giovanonni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Quantitative Trait Locus ◽  
Quantitative Trait ◽  
Target Genes ◽  
Gene List ◽  
Mendelian Randomisation ◽  
Causal Pathway ◽  
Trait Locus ◽  
Summary Data

AbstractBackgroundMultiple Sclerosis (MS) is a complex autoimmune disease caused by a combination of genetic and environmental factors. Translation of Genome-Wide Association Study (GWAS) findings in MS into therapeutics and effective preventive strategies has been limited to date.MethodsWe used Summary Data-Based Mendelian Randomisation (SMR) to synthesise findings from public expression quantitative trait locus (eQTL; eQTLgen and CAGE), methylation quantitative trait locus (mQTL; Lothian Birth Cohort and Brisbane Systems Genetics Study), and MS GWAS datasets (International Multiple Sclerosis Genetics Consortium). By correlating the effects of methylation on MS (M-2-MS), methylation on expression (M-2-E), and expression on MS susceptibility (E-2-MS), we prioritise genetic loci with strong evidence of causally influencing MS susceptibility. We overlay these findings onto a list of ‘druggable’ genes, i.e. genes which are currently, or could theoretically, be targeted by therapeutic compounds. We use GeNets and STRING to identify protein-protein interactions and druggable pathways enriched in our results. We extend these findings to a model of Epstein-Barr Virus-infected B cells, Lymphoblastoid Cell Lines (LCLs). We conducted a systematic review of prioritised genes using the Open Targets platform to identify completed and planned trials targeted prioritised genes in MS and related disease areas.ResultsExpression of 45 genes in peripheral was strongly associated with MS susceptibility (False discovery rate 0.05). Of these 45 genes, 20 encode a protein which is currently targeted by an existing therapeutic compound. These genes were enriched for Gene Ontology terms pertaining to immune system function and leukocyte signalling. We refined this prioritised gene list by restricting to loci where CpG site methylation was associated with MS susceptibility (M-2-MS), with gene expression (M-2-E), and where expression was associated with MS susceptibility (E-2-MS). This approach yielded a list of 15 prioritised druggable target genes for which there was evidence of a causal pathway linking methylation, expression, and MS. Five of these 15 genes are targeted by existing drugs (CD40, ERBB2, VEGFB, MERTK, and PARP1), and three were replicated in a smaller eQTL dataset (CD40, MERTK, and PARP1). In LCLs, SMR prioritised 7 druggable gene targets, of which only one was priortised by the multi-omic approach in peripheral blood (FCRL3). Systematic review of Open Targets revealed multiple early-phase trials targeting 13/20 prioritised genes in disorders related to MS.ConclusionsWe use public datasets and SMR to identify a list of prioritised druggable genetic targets in Multiple Sclerosis. We hope our findings could be translated into effective repurposing of existing drugs to provide novel therapies for MS and, potentially, provide a platform for developing preventive therapies.

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