Faculty Opinions recommendation of Abundant contribution of short tandem repeats to gene expression variation in humans.

Expression quantitative trait loci (eQTLs) are a key tool to dissect cellular processes mediating complex diseases. However, little is known about the role of repetitive elements as eQTLs. We report a genome-wide survey of the contribution of Short Tandem Repeats (STRs), one of the most polymorphic and abundant repeat classes, to gene expression in humans. Our survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays. We used variance partitioning to disentangle the contribution of eSTRs from linked SNPs and indels and found that eSTRs contribute 10%-15% of the cis-heritability mediated by all common variants. Functional genomic analyses showed that eSTRs are enriched in conserved regions, co-localize with regulatory elements, and are predicted to modulate histone modifications. Our results show that eSTRs provide a novel set of regulatory variants and highlight the contribution of repeats to the genetic architecture of quantitative human traits.

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Effects on gene expression and behavior of untagged short tandem repeats: the case of arginine vasopressin receptor 1a (AVPR1a) and externalizing behaviors

Translational Psychiatry ◽

10.1038/s41398-018-0120-z ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 5

Author(s):

Clare C Landefeld ◽

Colin A Hodgkinson ◽

Primavera A Spagnolo ◽

Cheryl A Marietta ◽

Pei-Hong Shen ◽

...

Keyword(s):

Gene Expression ◽

Arginine Vasopressin ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

Externalizing Behaviors ◽

Vasopressin Receptor ◽

And Behavior ◽

Short Tandem

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

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-021-00658-z ◽

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.

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Importance of polymorphic SNPs, short tandem repeats and structural variants for differential gene expression among inbred C57BL/6 and C57BL/10 substrains

10.1101/2020.03.16.993683 ◽

2020 ◽

Author(s):

Milad Mortazavi ◽

Yangsu Ren ◽

Shubham Saini ◽

Danny Antaki ◽

Celine St. Pierre ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

Expression Patterns ◽

Unintended Consequences ◽

Differentially Expressed ◽

Structural Variants ◽

Short Tandem ◽

New Mutations

AbstractC57BL/6J is the most widely used inbred mouse strain and is the basis for the mouse reference genome. In addition to C57BL/6J, several other C57BL/6 and C57BL/10 substrains exist. Previous studies have documented extensive phenotypic and genetic differences among these substrains, which are presumed to be due to the accumulation of new mutations. These differences can be used for genome wide association studies. They can also have unintended consequences for reproducibility when substrain differences are not properly accounted for. In this paper, we performed genomic sequencing and RNA-sequencing in the hippocampus of 9 C57BL/6 and 5 C57BL/10 substrains. We identified 985,329 SNPs, 150,344 Short Tandem Repeats (STR) and 896 Structural Variants (SV), out of which 330,178 SNPs and 14,367 STRs differentiated the C57BL/6 and C57BL/10 groups. We found several regions that contained dense polymorphisms. We also identified 578 differentially expressed genes for C57BL/6 substrains and 37 differentially expressed genes for C57BL/10 substrains (FDR < 0.01). We then identified nearby SNPs, STRs and SVs that matched the gene expression patterns. In so doing, we identified SVs in coding regions of Wdfy1, Ide, Fgfbp3 and Btaf1 that explain the expression patterns observed. We replicated several previously reported gene expression differences between substrains (Nnt, Gabra2) as well as many novel gene expression differences (e.g. Kcnc2). Our results illustrate the impact of new mutations on gene expression among these substrains and provides a resource for future mapping studies.

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

10.1101/714477 ◽

2019 ◽

Cited By ~ 3

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.

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

10.1101/495226 ◽

2018 ◽

Cited By ~ 3

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.

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