scholarly journals Massive variation of short tandem repeats with functional consequences across strains of Arabidopsis thaliana

2017 ◽  
Author(s):  
Maximilian O. Press ◽  
Rajiv C. McCoy ◽  
Ashley N. Hall ◽  
Joshua M. Akey ◽  
Christine Queitsch
Keyword(s):  
Arabidopsis Thaliana ◽  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Intron Retention ◽  
Purifying Selection ◽  
Genomic Variation ◽  
Functional Consequences ◽  
Short Tandem

AbstractShort tandem repeat (STR) mutations may be responsible for more than half of the mutations in eukaryotic coding DNA, yet STR variation is rarely examined as a contributor to complex traits. We assess the scope of this contribution across a collection of 96 strains of Arabidopsis thaliana by massively parallel STR genotyping. We found that 95% of examined STRs are polymorphic, with a median of six alleles per STR in these strains. Modest STR expansions are found in most strains, some of which have evident functional effects. For instance, three of six intronic STR expansions are associated with intron retention. Coding STRs are depleted of variation relative to non-coding STRs, consistent with the action of purifying selection, and some STRs show hypervariable patterns consistent with diversifying selection. Finally, we detect dozens of novel STR-phenotype associations that could not be detected with SNPs alone, validating several with follow-up experiments. Our results demonstrate that STRs comprise a large, unascertained reservoir of functionally relevant genomic variation.

scholarly journals Massive variation of short tandem repeats with functional consequences across strains of Arabidopsis thaliana

2018 ◽  
Vol 28 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Maximilian O. Press ◽  
Rajiv C. McCoy ◽  
Ashley N. Hall ◽  
Joshua M. Akey ◽  
Christine Queitsch
Keyword(s):  
Arabidopsis Thaliana ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Functional Consequences ◽  
Short Tandem

scholarly journals Properties of structural variants and short tandem repeats associated with gene expression and complex traits

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
David Jakubosky ◽  
◽  
Matteo D’Antonio ◽  
Marc Jan Bonder ◽  
Craig Smail ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Structural Variants ◽  
Short Tandem

scholarly journals A reference haplotype panel for genome-wide imputation of short tandem repeats

2018 ◽  
Author(s):  
Shubham Saini ◽  
Ileena Mitra ◽  
Nima Mousavi ◽  
Stephanie Feupe Fotsing ◽  
Melissa Gymrek
Keyword(s):  
Complex Traits ◽  
Large Scale ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Association Studies ◽  
Next Generation Sequencing Data ◽  
Genome Wide ◽  
Individual Snps ◽  
Reference Haplotype ◽  
Short Tandem

AbstractShort tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in a variety of complex traits. However, existing technologies focusing on single nucleotide polymorphisms (SNPs) have not allowed for systematic STR association studies. Here, we leverage next-generation sequencing data from 479 families to create a SNP+STR reference haplotype panel for genome-wide imputation of STRs into SNP data. Imputation achieved an average of 97% concordance between genotyped and imputed STR genotypes in an external dataset compared to 63% expected under a random model. Performance varied widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic forensics markers. We demonstrate that imputation increases power over individual SNPs to detect STR associations using simulated phenotypes and gene expression data. This resource will enable the first large-scale STR association studies using existing SNP datasets, and will likely yield new insights into complex traits.

scholarly journals Mapping short tandem repeats for liver gene expression traits helps prioritize potential causal variants for complex traits in pigs

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhongzi Wu ◽  
Huanfa Gong ◽  
Zhimin Zhou ◽  
Tao Jiang ◽  
Ziqi Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Genome Wide Association Study ◽  
Complex Trait ◽  
Validation Population ◽  
Causal Variants ◽  
Liver Gene ◽  
Short Tandem

Abstract Background Short tandem repeats (STRs) were recently found to have significant impacts on gene expression and diseases in humans, but their roles on gene expression and complex traits in pigs remain unexplored. This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds. Results We identified 5203 and 5868 significantly expression STRs (eSTRs, FDR < 1%) in the F6 and F7 populations, respectively, most of which could be reciprocally validated (π1 = 0.92). The eSTRs explained 27.5% of the cis-heritability of gene expression traits on average. We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs, respectively, which were significantly enriched in intron, ATAC peak, compartment A and H3K4me3 regions. We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs, which colocalized with epigenetic markers such as H3K27ac and ATAC peaks. These included eSTR of the CLPB, PGLS, PSMD6 and DHDH genes, which are linked with genome-wide association study (GWAS) SNPs for blood-related traits, leg conformation, growth-related traits, and meat quality traits, respectively. Conclusions This study provides insights into the effects of STRs on gene expression traits. The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.

scholarly journals Genomic properties of structural variants and short tandem repeats that impact gene expression and complex traits in humans

2019 ◽  
Author(s):  
David Jakubosky ◽  
Matteo D’Antonio ◽  
Marc Jan Bonder ◽  
Craig Smail ◽  
Margaret K.R. Donovan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Evolutionary Constraint ◽  
Structural Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Genomic Locations ◽  
Short Tandem

AbstractStructural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we show that different SV classes and STRs differentially impact gene expression and complex traits. Functional differences between SV classes and STRs include their genomic locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We also identified a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and showed they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that impact gene expression and human traits.

scholarly journals Evidence of transcription at polyT short tandem repeats

2019 ◽  
Author(s):  
Chloé Bessière ◽  
Manu Saraswat ◽  
Mathys Grapotte ◽  
Christophe Menichelli ◽  
Jordan A. Ramilowski ◽  
...  
Keyword(s):  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Specific Gene ◽  
Transcription Start Sites ◽  
Cap Analysis ◽  
Dna Tandem Repeats ◽  
Deep Learning Model ◽  
Short Tandem ◽  
Str Polymorphism

AbstractBackgroundUsing the Cap Analysis of Gene Expression technology, the FANTOM5 consortium provided one of the most comprehensive maps of Transcription Start Sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers.ResultsHere, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at short tandem repeats (STRs) corresponding to homopolymers of thymidines (T). Additional analyse confirm that these CAGEs are truly associated with transcriptionally active chromatin marks. Furthermore, we train a sequence-based deep learning model able to predict CAGE signal at T STRs with high accuracy (~81%) Extracting features learned by this model reveals that transcription at T STRs is mostly directed by STR length but also instructions lying in the downstream sequence. Excitingly, our model also predicts that genetic variants linked to human diseases affect this STR-associated transcription.ConclusionsTogether, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism. We also provide a new metric that can be considered in future studies of STR-related complex traits.

scholarly journals The variable ELF3 polyglutamine tract mediates complex epistatic interactions in Arabidopsis thaliana

2016 ◽  
Author(s):  
◽  
Christine Queitsch
Keyword(s):  
Arabidopsis Thaliana ◽  
Genetic Variation ◽  
Mutation Rate ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
High Mutation Rate ◽  
Hybrid Strategy ◽  
Coding Regions ◽  
Polyglutamine Tract ◽  
Short Tandem

ABSTRACTShort tandem repeats are hypervariable genetic elements that occur frequently in coding regions. Their high mutation rate readily generates genetic variation contributing to adaptive evolution and human diseases. We recently proposed that short tandem repeats are likely to engage in epistasis because they are well-positioned to compensate for genetic variation arising at other loci due to their high mutation rate. We previously reported that natural ELF3 polyglutamine variants cause reciprocal genetic incompatibilities in two divergent Arabidopsis thaliana backgrounds. Here, we dissected the genetic architecture of this incompatibility and used a yeast two-hybrid strategy to identify proteins whose physical interactions with ELF3 were modulated by polyglutamine tract length. Using these two orthogonal approaches, we identify specific genetic interactions and physical mechanisms by which the ELF3 polyglutamine tract may mediate the observed genetic incompatibilities. Our work elucidates how short tandem repeat variation, which is generally underascertained in population-scale sequencing, can contribute to phenotypic variation. Furthermore, our results support our proposal that highly variable STR loci can contribute disproportionately to the epistatic component of heritability.

scholarly journals Multi-tissue analysis reveals short tandem repeats as ubiquitous regulators of gene expression and complex traits

2018 ◽  
Author(s):  
Stephanie Feupe Fotsing ◽  
Jonathan Margoliash ◽  
Catherine Wang ◽  
Shubham Saini ◽  
Richard Yanicky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Tissue Expression ◽  
Genome Wide ◽  
Limited Power ◽  
Inflammatory Bowel ◽  
Sequencing And Expression ◽  
Short Tandem

AbstractShort tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and provide insights into putative mechanisms. Here, we leverage whole genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project (GTEx) to identify STRs for which repeat number is associated with expression of nearby genes (eSTRs). Our analysis reveals more than 28,000 eSTRs. We employ fine-mapping to quantify the probability that each eSTR is causal and characterize a group of the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published GWAS signals and implicate specific eSTRs in complex traits including height and schizophrenia, inflammatory bowel disease, and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes and will serve as a valuable resource for future studies of complex traits.

scholarly journals Short Tandem Repeats (STRs) as Biomarkers for the Quantitative Follow-Up of Chimerism after Stem Cell Transplantation: Methodological Considerations and Clinical Application

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 993
Author(s):  
Almudena Navarro-Bailón ◽  
Diego Carbonell ◽  
Asunción Escudero ◽  
María Chicano ◽  
Paula Muñiz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Mixed Chimerism ◽  
Hematopoietic Stem ◽  
Gold Standard Method ◽  
Short Tandem

Chimerism refers to the relative proportion of donor and recipient DNA after hematopoietic stem cell transplantation (HSCT) and its quantitative follow-up is of great clinical utility in this setting. PCR of short tandem repeats (STR-PCR) constitutes the gold standard method for chimerism quantification, although more sensitive PCR techniques (such as qPCR) have recently arisen. We compared the sensitivity and the quantification capacity of both techniques in patient samples and artificial mixtures and demonstrated adequate performance of both methods, with higher sensitivity of qPCR and better quantification skills of STR-PCR. By qPCR, we then prospectively followed up 57 patients that were in complete chimerism (CC) by STR-PCR. Twenty-seven patients (59%) showed 0.1–1% recipient DNA in the bone marrow. Only 4 patients presented 0.1–1% recipient DNA in peripheral blood (PB), and one of them relapsed. Finally, by qPCR, we retrospectively studied the last sample that showed CC by STR-PCR prior to relapse in 8 relapsed patients. At a median of 59 days prior to relapse, six patients presented mixed chimerism by qPCR in PB. Since both approaches have complementary characteristics, we conclude that different techniques should be applied in different clinical settings and therefore propose a methodological algorithm for chimerism follow-up after HSCT.

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