scholarly journals Genome-wide profiling of heritable and de novo STR variations

2016 ◽  
Author(s):  
Thomas Willems ◽  
Dina Zielinski ◽  
Assaf Gordon ◽  
Melissa Gymrek ◽  
Yaniv Erlich
Keyword(s):  
Tandem Repeats ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Genetic Diseases ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Short Tandem

AbstractShort tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases, population genetics applications, and forensic casework. However, STRs have proven problematic to genotype from high-throughput sequencing data. Here, we describe HipSTR, a novel haplotype-based method for robustly genotyping, haplotyping, and phasing STRs from whole genome sequencing data and report a genome-wide analysis and validation of de novo STR mutations.

scholarly journals The Mutational Dynamics of Short Tandem Repeats in Large, Multigenerational Families

2021 ◽  
Author(s):  
Cody J Steely ◽  
Scott Watkins ◽  
Lisa Baird ◽  
Lynn Jorde
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
De Novo ◽  
Friedreich Ataxia ◽  
Whole Genome Sequencing Data ◽  
Sequencing Data ◽  
Alu Elements ◽  
Str Loci ◽  
Genome Wide ◽  
Short Tandem

Short tandem repeats (STRs) are tandemly repeated sequences of 1-6 bp motifs. STRs compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. Here, to estimate the genome-wide pattern of mutations at STR loci, we analyzed blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. Using HipSTR we identified de novo STR mutations in the 2nd generation of these pedigrees. Analyzing ~1.6 million STR loci, we estimate the empircal de novo STR mutation rate to be 5.24*10-5 mutations per locus per generation. We find that perfect repeats mutate ~2x more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements (p < 2.2e-16). Approximately 30% of STR mutations occur within Alu elements, which compose only ~11% of the genome, and ~10% are found in LINE-1 insertions, which compose ~17% of the genome. Phasing these de novo mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be ~85, which is similar to the average number of observed de novo single nucleotide variants.

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 Detection and application of genome-wide variations in peach for association and genetic relationship analysis

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Liping Guan ◽  
Ke Cao ◽  
Yong Li ◽  
Jian Guo ◽  
Qiang Xu ◽  
...  
Keyword(s):  
Genetic Relationship ◽  
Dna Markers ◽  
High Throughput Sequencing ◽  
Prunus Persica ◽  
Genetic Research ◽  
Diploid Species ◽  
Sequencing Data ◽  
Relationship Analysis ◽  
Genome Wide ◽  
A Genome

Abstract Background Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8386~12,298 structure variants (SVs), 2111~2581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach.

Next generation sequencing allows deeper analysis and understanding of genomes and transcriptomes including aspects to fertility

2011 ◽  
Vol 23 (1) ◽  
pp. 75 ◽  
Author(s):  
Thomas Werner
Keyword(s):  
Next Generation Sequencing ◽  
Transcriptional Control ◽  
Target Genes ◽  
De Novo ◽  
Alternative Promoters ◽  
Next Generation ◽  
Sequencing Data ◽  
Genome Wide ◽  
A Genome ◽  
Generation Sequencing

Reproduction and fertility are controlled by specific events naturally linked to oocytes, testes and early embryonal tissues. A significant part of these events involves gene expression, especially transcriptional control and alternative transcription (alternative promoters and alternative splicing). While methods to analyse such events for carefully predetermined target genes are well established, until recently no methodology existed to extend such analyses into a genome-wide de novo discovery process. With the arrival of next generation sequencing (NGS) it becomes possible to attempt genome-wide discovery in genomic sequences as well as whole transcriptomes at a single nucleotide level. This does not only allow identification of the primary changes (e.g. alternative transcripts) but also helps to elucidate the regulatory context that leads to the induction of transcriptional changes. This review discusses the basics of the new technological and scientific concepts arising from NGS, prominent differences from microarray-based approaches and several aspects of its application to reproduction and fertility research. These concepts will then be illustrated in an application example of NGS sequencing data analysis involving postimplantation endometrium tissue from cows.

scholarly journals Population-level genome-wide STR typing in Plasmodium species reveals higher resolution population structure and genetic diversity relative to SNP typing

2021 ◽  
Author(s):  
Jiru Han ◽  
Jacob E Munro ◽  
Anthony Kocoski ◽  
Alyssa E Barry ◽  
Melanie Bahlo
Keyword(s):  
Genetic Diversity ◽  
Large Scale ◽  
Tandem Repeats ◽  
Plasmodium Species ◽  
Whole Genome Sequence ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Genome Wide ◽  
Field Samples

Short tandem repeats (STRs) are highly informative genetic markers that have been used extensively in population genetics analysis. They are an important source of genetic diversity and can also have functional impact. Despite the availability of bioinformatic methods that permit large-scale genome-wide genotyping of STRs from whole genome sequencing data, they have not previously been applied to sequencing data from large collections of malaria parasite field samples. Here, we have genotyped STRs using HipSTR in more than 3,000 Plasmodium falciparum and 174 Plasmodium vivax published whole-genome sequence data from samples collected across the globe. High levels of noise and variability in the resultant callset necessitated the development of a novel method for quality control of STR genotype calls. A set of high-quality STR loci (6,768 from P. falciparum and 3,496 from P. vivax) were used to study Plasmodium genetic diversity, population structures and genomic signatures of selection and these were compared to genome-wide single nucleotide polymorphism (SNP) genotyping data. In addition, the genome-wide information about genetic variation and other characteristics of STRs in P. falciparum and P. vivax have been made available in an interactive web-based R Shiny application PlasmoSTR (https://github.com/bahlolab/PlasmoSTR).

scholarly journals Detection and application of genome-wide variations in peach for association and genetic relationship analysis

2019 ◽  
Author(s):  
Liping Guan ◽  
ke Cao ◽  
yong Li ◽  
jian guo ◽  
qiang xu ◽  
...  
Keyword(s):  
Genetic Relationship ◽  
Dna Markers ◽  
High Throughput Sequencing ◽  
Prunus Persica ◽  
Genetic Research ◽  
Diploid Species ◽  
Sequencing Data ◽  
Relationship Analysis ◽  
Genome Wide ◽  
A Genome

Abstract Background: Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results: In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8,386~12,298 structure variants (SVs), 2,111~2,581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions: The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach.

scholarly journals Detection and application of genome-wide variations in peach for association and genetic relationship analysis

2019 ◽  
Author(s):  
Liping Guan ◽  
ke Cao ◽  
yong Li ◽  
jian guo ◽  
qiang xu ◽  
...  
Keyword(s):  
Genetic Relationship ◽  
Dna Markers ◽  
High Throughput Sequencing ◽  
Prunus Persica ◽  
Genetic Research ◽  
Diploid Species ◽  
Sequencing Data ◽  
Relationship Analysis ◽  
Genome Wide ◽  
A Genome

Abstract Abstract Background: Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results: In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8,386~12,298 structure variants (SVs), 2,111~2,581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions: The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach.

scholarly journals fluff: exploratory analysis and visualization of high-throughput sequencing data

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2209 ◽  
Author(s):  
Georgios Georgiou ◽  
Simon J. van Heeringen
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Developmental Stages ◽  
Command Line ◽  
Clustering Methods ◽  
Sequencing Data ◽  
Link Type ◽  
High Throughput Sequencing Data ◽  
Genome Wide ◽  
Genome Wide Data

Summary.In this article we describe fluff, a software package that allows for simple exploration, clustering and visualization of high-throughput sequencing data mapped to a reference genome. The package contains three command-line tools to generate publication-quality figures in an uncomplicated manner using sensible defaults. Genome-wide data can be aggregated, clustered and visualized in a heatmap, according to different clustering methods. This includes a predefined setting to identify dynamic clusters between different conditions or developmental stages. Alternatively, clustered data can be visualized in a bandplot. Finally, fluff includes a tool to generate genomic profiles. As command-line tools, the fluff programs can easily be integrated into standard analysis pipelines. The installation is straightforward and documentation is available athttp://fluff.readthedocs.org.Availability.fluff is implemented in Python and runs on Linux. The source code is freely available for download athttps://github.com/simonvh/fluff.

scholarly journals NGSEP3: accurate variant calling across species and sequencing protocols

2019 ◽  
Vol 35 (22) ◽  
pp. 4716-4723 ◽  
Author(s):  
Daniel Tello ◽  
Juanita Gil ◽  
Cristian D Loaiza ◽  
John J Riascos ◽  
Nicolás Cardozo ◽  
...  
Keyword(s):  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
High Throughput Sequencing ◽  
Variant Calling ◽  
Real Data ◽  
Supplementary Information ◽  
Sequencing Data ◽  
Comparative Accuracy ◽  
Downstream Analysis ◽  
Short Tandem

Abstract Motivation Accurate detection, genotyping and downstream analysis of genomic variants from high-throughput sequencing data are fundamental features in modern production pipelines for genetic-based diagnosis in medicine or genomic selection in plant and animal breeding. Our research group maintains the Next-Generation Sequencing Experience Platform (NGSEP) as a precise, efficient and easy-to-use software solution for these features. Results Understanding that incorrect alignments around short tandem repeats are an important source of genotyping errors, we implemented in NGSEP new algorithms for realignment and haplotype clustering of reads spanning indels and short tandem repeats. We performed extensive benchmark experiments comparing NGSEP to state-of-the-art software using real data from three sequencing protocols and four species with different distributions of repetitive elements. NGSEP consistently shows comparative accuracy and better efficiency compared to the existing solutions. We expect that this work will contribute to the continuous improvement of quality in variant calling needed for modern applications in medicine and agriculture. Availability and implementation NGSEP is available as open source software at http://ngsep.sf.net. Supplementary information Supplementary data are available at Bioinformatics online.

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