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.

Population Genetics of Y-Chromosome Short Tandem Repeats in Humans

1997 ◽  
Vol 45 (3) ◽  
pp. 265-270 ◽  
Author(s):  
Anna Pérez-Lezaun ◽  
Francesc Calafell ◽  
Mark Seielstad ◽  
Eva Mateu ◽  
David Comas ◽  
...  
Keyword(s):  
Population Genetics ◽  
Y Chromosome ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Short Tandem

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 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 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.

Short Tandem Repeats and Genetic Variation

2010 ◽  
pp. 297-306 ◽  
Author(s):  
Bo Eskerod Madsen ◽  
Palle Villesen ◽  
Carsten Wiuf
Keyword(s):  
Genetic Variation ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Short Tandem

scholarly journals APOBEC mutagenesis is low in most types of non-B DNA structures, unlike other types of cancer mutagenesis

2021 ◽  
Author(s):  
Gennady V Ponomarev ◽  
Bulat Fatykhov ◽  
Vladimir A Nazarov ◽  
Ruslan Abasov ◽  
Evgeny Shvarov ◽  
...  
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
Somatic Mutations ◽  
Direct Repeats ◽  
Uv Mutagenesis ◽  
Dna Structures ◽  
G Quadruplex ◽  
The Impact ◽  
Very High ◽  
Short Tandem

While somatic mutations are known to be enriched in genome regions with non-canonical DNA secondary structure, the impact of particular mutagens still needs to be elucidated. Here, we demonstrate that in human cancers, the APOBEC mutagenesis is not enriched in direct repeats, mirror repeats, short tandem repeats, and G-quadruplexes, and even decreased below its level in B-DNA for cancer samples with very high APOBEC activity. In contrast, we observe that the APOBEC-induced mutational density is positively associated with APOBEC activity in inverted repeats (cruciform structures), where the impact of cytosine at the 3'-end of the hairpin loop is substantial. Surprisingly, the APOBEC-signature mutation density per TC motif in the single-stranded DNA of a G-quadruplex (G4) is lower than in the four-stranded part of G4 and in B-DNA. The APOBEC mutagenesis, as well as the UV-mutagenesis in melanoma samples are absent in Z-DNA regions, due to depletion of their mutational signature motifs.

scholarly journals Big data and innovative bioinformatics approaches in personalized genomic medicine

2021 ◽  
Vol 41 ◽  
pp. 01003
Author(s):  
Joris A. Veltman
Keyword(s):  
Genetic Variation ◽  
Genome Sequence ◽  
Developmental Disorders ◽  
Genomic Medicine ◽  
Population Variation ◽  
Biological Information ◽  
Management Approach ◽  
Specific Information ◽  
A Genome ◽  
The Impact

The field of human genetics has been radically changed by the introduction of massive parallel sequencing, also called next generation sequencing, approaches. Instead of studying a single gene or a few genetic variants, nowadays we can study genetic variation present in all genes and even throughout the entire human genome. For the first time in history, we can really study what makes us unique and use that to explain differences in for example disease susceptibility or response to treatment. In rare disease, genetics research is essential to identify the molecular diagnosis that provides the basis for a personalized patient management approach. It allows for more precise answers about the underlying cause and family recurrence risk, but also aids in optimizing treatment plans aimed at reducing co-morbidities and providing information about potential drugs or participation in drug trials, with an increasing number focused on gene therapy. These high-throughput sequencing technologies generate enormous amounts of data in order to assemble a genome and identify all of the variation present at different levels, from single nucleotide variations to chromosomal abnormalities. In addition, a genome sequence of a person in itself is not very useful. Value is derived from annotation of all the variation, and integration of the genome sequence with information about the patient involved (clinical information, disease-specific information, family history) as well as biological information (gene as well as variant-specific information, including population variation frequency, pathogenicity predictions, gene-expression information, etc). In this presentation, I will give an overview of the impact of genomics on the diagnosis of patients with rare developmental disorders and fertility disorders. I will highlight the importance of innovative bioinformatics approaches to detect and interpret genetic variation in a clinical context. Also, I will highlight some of the challenges that individual research and diagnostics units face in dealing with the data generated, discuss some of the ethical/privacy issues related to these approaches and discuss some of the latest genomics technologies being developed and validated.

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.

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