CAGm: a repository of germline microsatellite variations in the 1000 genomes project

Kinney, Nicholas A.; Titus-Glover, Kyle; Wren, Jonathan D.; Varghese, Robin; Michalak, Pawel; Han, Liang; Anandakrishnan, Ramu; Pulenthiran, Arichanah; Kang, Lin; Garner, Harold R.

doi:10.1093/nar/gky969

Cited by 10 publications

(6 citation statements)

References 48 publications

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“…CAGm database created by Kinney et al . is a rich resource that catalogues polymorphic 625k microsatellites as observed across the 1000 genome population and covers the basic understanding of the variability of length of STRs and other features for data extraction and analysis with respect to the genotype information ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

STRIDE-DB: a comprehensive database for exploration of instability and phenotypic relevance of short tandem repeats in the human genome

Uppili,

Faruq

2024

Database

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Short Tandem Repeats (STRs) are genetic markers made up of repeating DNA sequences. The variations of the STRs are widely studied in forensic analysis, population studies and genetic testing for a variety of neuromuscular disorders. Understanding polymorphic STR variation and its cause is crucial for deciphering genetic information and finding links to various disorders. In this paper, we present STRIDE-DB, a novel and unique platform to explore STR Instability and its Phenotypic Relevance, and a comprehensive database of STRs in the human genome. We utilized RepeatMasker to identify all the STRs in the human genome (hg19) and combined it with frequency data from the 1000 Genomes Project. STRIDE-DB, a user-friendly resource, plays a pivotal role in investigating the relationship between STR variation, instability and phenotype. By harnessing data from genome-wide association studies (GWAS), ClinVar database, Alu loci, Haploblocks in genome and Conservation of the STRs, it serves as an important tool for researchers exploring the variability of STRs in the human genome and its direct impact on phenotypes. STRIDE-DB has its broad applicability and significance in various research domains like forensic sciences and other repeat expansion disorders. Database URL: https://stridedb.igib.res.in.

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Section: Discussionmentioning

confidence: 99%

STRIDE-DB: a comprehensive database for exploration of instability and phenotypic relevance of short tandem repeats in the human genome

Uppili,

Faruq

2024

Database

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“…Notwithstanding these limitations, several bioinformatics tools for the inference of complex structural rearrangements from short-read sequencing data have been developed in recent years [62][63][64][65][66]. Although these tools, which are the subject of a comprehensive recent review [62], have enabled the detection of a fraction of the 'human variome', which was previously deemed inaccessible to short-read sequencing technologies, their performance still does not meet the minimum standards required for clinical diagnostics in terms of sensitivity and specificity [67,68], furthermore an unsatisfactory overall agreement is observed when multiple methods are applied [69].…”

Section: Detection Of Str Expansions Using 2nd-generation Sequencing ...mentioning

confidence: 99%

Critical assessment of bioinformatics methods for the characterization of pathological repeat expansions with single-molecule sequencing data

Chiara

Zambelli

Picardi

et al. 2019

Briefings in Bioinformatics

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A number of studies have reported the successful application of single-molecule sequencing technologies to the determination of the size and sequence of pathological expanded microsatellite repeats over the last 5 years. However, different custom bioinformatics pipelines were employed in each study, preventing meaningful comparisons and somewhat limiting the reproducibility of the results. In this review, we provide a brief summary of state-of-the-art methods for the characterization of expanded repeats alleles, along with a detailed comparison of bioinformatics tools for the determination of repeat length and sequence, using both real and simulated data. Our reanalysis of publicly available human genome sequencing data suggests a modest, but statistically significant, increase of the error rate of single-molecule sequencing technologies at genomic regions containing short tandem repeats. However, we observe that all the methods herein tested, irrespective of the strategy used for the analysis of the data (either based on the alignment or assembly of the reads), show high levels of sensitivity in both the detection of expanded tandem repeats and the estimation of the expansion size, suggesting that approaches based on single-molecule sequencing technologies are highly effective for the detection and quantification of tandem repeat expansions and contractions.

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“…Recent inroads were made by our own efforts to characterize germline microsatellites variations in the 1000 Genomes Project. First, we established a database of microsatellite variation across population, ethnicity (super population) and gender [ 20 ]. On the heels of this effort, we identified 3,984 ethnically biased microsatellite loci (EBML) in Africans, South Asians, East Asians, Europeans, and Americans [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans

et al. 2021

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Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.

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CAGm: a repository of germline microsatellite variations in the 1000 genomes project

Cited by 10 publications

References 48 publications

STRIDE-DB: a comprehensive database for exploration of instability and phenotypic relevance of short tandem repeats in the human genome

STRIDE-DB: a comprehensive database for exploration of instability and phenotypic relevance of short tandem repeats in the human genome

Critical assessment of bioinformatics methods for the characterization of pathological repeat expansions with single-molecule sequencing data

Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans

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