Population-scale whole genome sequencing identifies 271 highly polymorphic short tandem repeats from Japanese population

Uniparental disomy (UPD) is a rare type of chromosomal aberration that has sometimes been detected in paternity testing. We examined a 3-person family (father, mother, daughter) first by using short tandem repeat markers, which revealed 4 markers, TPOX, D2S1338, D2S1772, and D2S441, on chromosome 2 that were not transmitted in a Mendelian style. We then performed whole genome sequencing (WGS) to determine the range of the UPD. Chromosome 2 in the daughter showed a complete paternal UPD. To the best of our knowledge, this is the 4th case of complete paternal UPD of chromosome 2 with no clinical phenotype. Our study suggests that WGS, when performed to enhance the accuracy and reliability of parentage testing, can provide a powerful method to detect an UPD.

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Comparison of routine field epidemiology and whole genome sequencing to identify tuberculosis transmission in a remote setting

Epidemiology and Infection ◽

10.1017/s0950268820000072 ◽

2020 ◽

Vol 148 ◽

Cited By ~ 1

Author(s):

J. L. Guthrie ◽

L. Strudwick ◽

B. Roberts ◽

M. Allen ◽

J. McFadzen ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Tandem Repeats ◽

Variable Number ◽

Yukon Territory ◽

Contact Tracing ◽

Whole Genome ◽

Attitudes And Practices ◽

Genomic Epidemiology ◽

Recent Transmission

Abstract Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

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Whole Genome Sequencing for Tracing Geographical Origin of Imported Cases of Human Brucellosis in Sweden

Microorganisms ◽

10.3390/microorganisms7100398 ◽

2019 ◽

Vol 7 (10) ◽

pp. 398 ◽

Cited By ~ 4

Author(s):

Sacchini ◽

Wahab ◽

Di Giannatale ◽

Zilli ◽

Abass ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Tandem Repeats ◽

Brucella Melitensis ◽

Geographic Origin ◽

Variable Number ◽

Human Brucellosis ◽

Whole Genome ◽

Multiple Loci ◽

Imported Cases

Human infections with Brucella melitensis are occasionally reported in Sweden, despite the fact that the national flocks of sheep and goats are officially free from brucellosis. The aim of our study was to analyze 103 isolates of B. melitensis collected from patients in Sweden between 1994 and 2016 and determine their putative geographic origin using whole genome sequencing (WGS)-based tools. The majority of the strains were assigned to East Mediterranean and African lineages. Both in silico Multiple Loci VNTR (Variable Number of Tandem Repeats) Analysis (MLVA) and core genome Multilocus Sequence Typing (cgMLST) analyses identified countries of the Middle East as the most probable source of origin of the majority of the strains. Isolates collected from patients with travel history to Iraq or Syria were often associated with genotypes from Turkey, as the cgMLST profiles from these countries clustered together. Sixty strains were located within a distance of 20 core genes to related genotypes from the publicly available database, and for eighteen isolates, the closest genotype was different by more than 50 loci. Our study showed that WGS based tools are effective in tracing back the geographic origin of infection of patients with unknown travel status, provided that public sequences from the location of the source are available.

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Body temperature predicts maximum microsatellite length in mammals

Biology Letters ◽

10.1098/rsbl.2008.0209 ◽

2008 ◽

Vol 4 (4) ◽

pp. 399-401 ◽

Cited By ~ 5

Author(s):

William Amos ◽

Andrew Clarke

Keyword(s):

Body Temperature ◽

Genome Sequencing ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

Temperature Dependent ◽

Repeat Number ◽

Stability Threshold ◽

Marker Loci ◽

Microsatellite Evolution ◽

Short Tandem

A long-standing mystery in genome evolution is why short tandem repeats vary so much in length and frequency. Here, we test the hypothesis that body temperature acts to influence the rate and nature of slippage-based mutations. Using the data from both 28 species where genome sequencing is advanced and 76 species from which marker loci have been published, we show that in mammals, maximum repeat number is inversely correlated with body temperature, with warmer-blooded species having shorter ‘long’ microsatellites. Our results support a model of microsatellite evolution in which maximum length is limited by a temperature-dependent stability threshold.

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CNView: a visualization and annotation tool for copy number variation from whole-genome sequencing

10.1101/049536 ◽

2016 ◽

Cited By ~ 6

Author(s):

Ryan L. Collins ◽

Matthew R. Stone ◽

Harrison Brand ◽

Joseph T. Glessner ◽

Michael E. Talkowski

Keyword(s):

Copy Number Variation ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Copy Number ◽

Software Tool ◽

Whole Genome ◽

Data Types ◽

Recent Emergence ◽

Number Variation ◽

Population Scale

AbstractSummaryCopy number variation (CNV) is a major component of structural differences between individual genomes. The recent emergence of population-scale whole-genome sequencing (WGS) datasets has enabled genome-wide CNV delineation. However, molecular validation at this scale is impractical, so visualization is an invaluable preliminary screening approach when evaluating CNVs. Standardized tools for visualization of CNVs in large WGS datasets are therefore in wide demand.Methods & ResultsTo address this demand, we developed a software tool, CNView, for normalized visualization, statistical scoring, and annotation of CNVs from population-scale WGS datasets. CNView surmounts challenges of sequencing depth variability between individual libraries by locally adapting to cohort-wide variance in sequencing uniformity at any locus. Importantly, CNView is broadly extensible to any reference genome assembly and most current WGS data types.Availability and ImplementationCNView is written in R, is supported on OS X, MS Windows, and Linux, and is freely distributed under the MIT license. Source code and documentation are available from https://github.com/RCollins13/[email protected]

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Analyses of X-linked and autosomal genetic variation in population-scale whole genome sequencing

Nature Genetics ◽

10.1038/ng.877 ◽

2011 ◽

Vol 43 (8) ◽

pp. 741-743 ◽

Cited By ~ 59

Author(s):

Srikanth Gottipati ◽

Leonardo Arbiza ◽

Adam Siepel ◽

Andrew G Clark ◽

Alon Keinan

Keyword(s):

Genetic Variation ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Population Scale

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STRipy: a graphical application for enhanced genotyping of pathogenic short tandem repeats in sequencing data

10.1101/2021.06.13.448220 ◽

2021 ◽

Author(s):

Andreas Halman ◽

Egor Dolzhenko ◽

Alicia Oshlack

Keyword(s):

Genome Sequencing ◽

Fragment Length ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

High Throughput Sequencing ◽

Causal Variant ◽

Sequencing Data ◽

Pathogenic Variants ◽

Set Up ◽

Short Tandem

AbstractShort tandem repeats (STRs) are highly polymorphic with high mutation rates and expansions of STRs have been implicated as the causal variant in diseases. The application of genome sequencing in patients has recently allowed many new discoveries with over 50 disease causing loci known to date. There are several tools which allow genotyping of STRs from high-throughput sequencing (HTS) data. However, running these tools out of the box only allow around half of the known disease-causing loci to be genotyped, with lengths often limited to either read or fragment length which is less than the pathogenic cut-off for some diseases. While analysis tools can be customised to genotype extra loci, this requires proficiency in bioinformatics to set up, use, and analyse the resulting data, limiting their widespread usage by other researchers and clinicians.To address these issues, we have created a new software called STRipy that has an intuitive graphical interface and requires no specific skills for usage, thus significantly simplifying detection of STRs expansions from human HTS data. STRipy is able to target all known disease-causing STRs with genotyping performed with an established tool, ExpansionHunter, that is incorporated into the software. We have created additional functionality into STRipy to work with long alleles exceeding the fragment length.STRipy was validated using over 60 thousand simulated samples and was shown to work on whole genome sequencing of biological samples with pathogenic variants. Finally, we have used STRipy to acquire genotypes of pathogenic loci for thousands of samples from various populations which are provided to the user along with the data from the literature to assist with results interpretation. We believe the simplicity and breadth of STRipy will increase the testing of STR diseases in current datasets resulting in further diagnoses of rare diseases caused by STRs expansions.

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