scholarly journals Abundant contribution of short tandem repeats to gene expression variation in humans

2015 ◽  
Author(s):  
Melissa Gymrek ◽  
Thomas Willems ◽  
Haoyang Zeng ◽  
Barak Markus ◽  
Mark J Daly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Regulatory Elements ◽  
Variance Partitioning ◽  
Cellular Processes ◽  
Regulatory Variants ◽  
A Genome ◽  
Significant Expression ◽  
Short Tandem

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.

scholarly journals Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome

2021 ◽  
Author(s):  
Linda Zhou ◽  
Chunmin Ge ◽  
Thomas Malachowski ◽  
Ji Hun Kim ◽  
Keerthivasan Raanin Chandradoss ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Fragile X ◽  
Repeat Expansion ◽  
Genome Wide ◽  
A Genome ◽  
In Trans ◽  
Surveillance Mechanism ◽  
Short Tandem

AbstractShort tandem repeat (STR) instability is causally linked to pathologic transcriptional silencing in a subset of repeat expansion disorders. In fragile X syndrome (FXS), instability of a single CGG STR tract is thought to repress FMR1 via local DNA methylation. Here, we report the acquisition of more than ten Megabase-sized H3K9me3 domains in FXS, including a 5-8 Megabase block around FMR1. Distal H3K9me3 domains encompass synaptic genes with STR instability, and spatially co-localize in trans concurrently with FMR1 CGG expansion and the dissolution of TADs. CRISPR engineering of mutation-length FMR1 CGG to normal-length preserves heterochromatin, whereas cut-out to pre-mutation-length attenuates a subset of H3K9me3 domains. Overexpression of a pre-mutation-length CGG de-represses both FMR1 and distal heterochromatinized genes, indicating that long-range H3K9me3-mediated silencing is exquisitely sensitive to STR length. Together, our data uncover a genome-wide surveillance mechanism by which STR tracts spatially communicate over vast distances to heterochromatinize the pathologically unstable genome in FXS.One-Sentence SummaryHeterochromatinization of distal synaptic genes with repeat instability in fragile X is reversible by overexpression of a pre-mutation length CGG tract.

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 Abundant contribution of short tandem repeats to gene expression variation in humans

2015 ◽  
Vol 48 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Melissa Gymrek ◽  
Thomas Willems ◽  
Audrey Guilmatre ◽  
Haoyang Zeng ◽  
Barak Markus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Gene Expression Variation ◽  
Expression Variation ◽  
Short Tandem

scholarly journals A worldwide map of swine short tandem repeats and their associations with evolutionary and environmental adaptations

2021 ◽  
Vol 53 (1) ◽  
Author(s):  
Zhongzi Wu ◽  
Huanfa Gong ◽  
Mingpeng Zhang ◽  
Xinkai Tong ◽  
Huashui Ai ◽  
...  
Keyword(s):  
Environmental Variables ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Nucleotide Polymorphisms ◽  
Loss Of Function ◽  
Sequencing Data ◽  
Wild Boars ◽  
A Genome ◽  
Average Annual Temperature ◽  
Short Tandem

Abstract Background Short tandem repeats (STRs) are genetic markers with a greater mutation rate than single nucleotide polymorphisms (SNPs) and are widely used in genetic studies and forensics. However, most studies in pigs have focused only on SNPs or on a limited number of STRs. Results This study screened 394 deep-sequenced genomes from 22 domesticated pig breeds/populations worldwide, wild boars from both Europe and Asia, and numerous outgroup Suidaes, and identified a set of 878,967 polymorphic STRs (pSTRs), which represents the largest repository of pSTRs in pigs to date. We found multiple lines of evidence that pSTRs in coding regions were affected by purifying selection. The enrichment of trinucleotide pSTRs in coding sequences (CDS), 5′UTR and H3K4me3 regions suggests that trinucleotide STRs serve as important components in the exons and promoters of the corresponding genes. We demonstrated that, compared to SNPs, pSTRs provide comparable or even greater accuracy in determining the breed identity of individuals. We identified pSTRs that showed significant population differentiation between domestic pigs and wild boars in Asia and Europe. We also observed that some pSTRs were significantly associated with environmental variables, such as average annual temperature or altitude of the originating sites of Chinese indigenous breeds, among which we identified loss-of-function and/or expanded STRs overlapping with genes such as AHR, LAS1L and PDK1. Finally, our results revealed that several pSTRs show stronger signals in domestic pig—wild boar differentiation or association with the analysed environmental variables than the flanking SNPs within a 100-kb window. Conclusions This study provides a genome-wide high-density map of pSTRs in diverse pig populations based on genome sequencing data, enabling a more comprehensive characterization of their roles in evolutionary and environmental adaptation.

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

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.

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 Short Tandem Repeats as a High-Resolution Marker for Capturing Recent Orangutan Population Evolution

2021 ◽  
Vol 1 ◽  
Author(s):  
Alina-Alexandra Voicu ◽  
Michael Krützen ◽  
Tugce Bilgin Sonay
Keyword(s):  
Population Genetics ◽  
Genetic Variation ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Demographic History ◽  
Population Variation ◽  
Local Adaptations ◽  
A Genome ◽  
The Impact ◽  
Short Tandem

The genus Pongo is ideal to study population genetics adaptation, given its remarkable phenotypic divergence and the highly contrasting environmental conditions it’s been exposed to. Studying its genetic variation bears the promise to reveal a motion picture of these great apes’ evolutionary and adaptive history, and also helps us expand our knowledge of the patterns of adaptation and evolution. In this work, we advance the understanding of the genetic variation among wild orangutans through a genome-wide study of short tandem repeats (STRs). Their elevated mutation rate makes STRs ideal markers for the study of recent evolution within a given population. Current technological and algorithmic advances have rendered their sequencing and discovery more accurate, therefore their potential can be finally leveraged in population genetics studies. To study patterns of population variation within the wild orangutan population, we genotyped the short tandem repeats in a population of 21 individuals spanning four Sumatran and Bornean (sub-) species and eight Southeast Asian regions. We studied the impact of sequencing depth on our ability to genotype STRs and found that the STR copy number changes function as a powerful marker, correctly capturing the demographic history of these populations, even the divergences as recent as 10 Kya. Moreover, gene ontology enrichments for genes close to STR variants are aligned with local adaptations in the two islands. Coupled with more advanced STR-compatible population models, and selection tests, genomic studies based on STRs will be able to reduce the gap caused by the missing heritability for species with recent adaptations.

Sign in / Sign up

Export Citation Format

Share Document