MSDB: a comprehensive, annotated database of microsatellites

Avvaru, Akshay Kumar; Sharma, Deepak; Mishra, Rakesh K.; Sowpati, Divya Tej

doi:10.1093/nar/gkz886

Cited by 24 publications

(26 citation statements)

References 23 publications

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“…We next aimed to harness the information from our high-throughput assay to examine the impact of DNA polymerase stalling at STRs on their genomic representation. Using data from the MicroSatellite DataBase [ 3 ] reporting ~ 4,500,000 STR loci within the human genome, we found that the relative abundance of each of the 501 unique double-stranded motifs directly anticorrelates with the ability of the motif to stall DNA polymerase (Fig. 5 a) suggesting that STRs capable of significant secondary structure are deleterious.…”

Section: Resultsmentioning

confidence: 99%

“…Genomic coordinates of STRs from 6 eukaryotic genomes were recovered from the MicroSatellite DataBase [3]. The analysed genomes were Homo sapiens (hg38), Mus musculus (mm10), Gallus gallus (galGal6), Danio rerio (dm6), Drosophila melanogaster (dm6) and Saccharomyces cerevisiae (sacCer3).…”

Section: Abundance and Length Of Eukaryotic Strsmentioning

confidence: 99%

“…Amongst DNA repeats, motifs of 1 to 6 nucleotides repeated in a head-to-tail manner, known as short tandem repeats (STRs) or microsatellites, have attracted extensive attention due to their highly polymorphic nature and consequent applications in forensic DNA fingerprinting, genetic linkage analysis and the study of population dynamics [2]. STRs are ubiquitous in eukaryotic genomes, with~4,500,000 loci covering up to 2.5% of the human genome [3]. They exhibit mutation rates that are orders of magnitude higher than for other variant types such as single nucleotide polymorphisms (SNP) or copy number variations [4,5].…”

Section: Introductionmentioning

confidence: 99%

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DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats

2020

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Background: Short tandem repeats (STRs) contribute significantly to de novo mutagenesis, driving phenotypic diversity and genetic disease. Although highly diverse, their repetitive sequences induce DNA polymerase slippage and stalling, leading to length and sequence variation. However, current studies of DNA synthesis through STRs are restricted to a handful of selected sequences, limiting our broader understanding of their evolutionary behaviour and hampering the characterisation of the determinants of their abundance and stability in eukaryotic genomes. Results: We perform a comprehensive analysis of DNA synthesis at all STR permutations and interrogate the impact of STR sequence and secondary structure on their genomic representation and mutability. To do this, we developed a highthroughput primer extension assay that allows monitoring of the kinetics and fidelity of DNA synthesis through 20,000 sequences comprising all STR permutations in different lengths. By combining these measurements with population-scale genomic data, we show that the response of a model replicative DNA polymerase to variously structured DNA is sufficient to predict the complex genomic behaviour of STRs, including abundance and mutational constraints. We demonstrate that DNA polymerase stalling at DNA structures induces error-prone DNA synthesis, which constrains STR expansion. Conclusions: Our data support a model in which STR length in eukaryotic genomes results from a balance between expansion due to polymerase slippage at repeated DNA sequences and point mutations caused by error-prone DNA synthesis at DNA structures.

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Section: Resultsmentioning

confidence: 99%

Section: Abundance and Length Of Eukaryotic Strsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats

2020

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“…First, we downloaded the virus integration site information from the VISDB(Tang et al, 2020) and we lifted it over to the hg19 version using the liftover tool from the UCSC Genome Browser since FusionAI’s training was done based on the sequence of hg19 version (Navarro Gonzalez et al, 2021). We integrated 13 types of repeats (Alu repeats, A-Phased repeats, Directed repeats, DNA transposons, “G-Quadruplex, forming repeats”, Inverted repeats, L1 repeats, L2 repeats, “Low_complexity, A/T rich regions”, Microsatellites, MIR repeats, Mirror repeats, and Z-DNA motifs) from RepeatMasker (Bao et al, 2015) and MicroSatellite DataBase (MSDB) (Avvaru et al, 2020). For the diverse types of structural variants including the copy number variants, we downloaded the arranged breakpoint information of the structural variants from dbVar (Lappalainen et al, 2013).…”

Section: Methods Detailsmentioning

confidence: 99%

Deep Learning Approach to Genomic Breakage Study from Primary Sequence

Kim

Liu

et al. 2021

Preprint

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Identifying the molecular mechanisms related to genomic breakage is an important goal of cancer mechanism studies. Among the diverse location of the breakpoints of structural variants, the fusion genes, which have the breakpoints in the gene bodies and typically identified from RNA-seq data, can provide a highlighted structural variant resource for studying the genomic breakages with expression and potential pathogenic impacts. In this study, we developed FusionAI which utilizes deep learning to predict gene fusion breakpoints based on primary sequences and let us identify fusion breakage code and genomic context. FusionAI leverages the known fusion breakpoints to provide a prediction model of the fusion genes from the primary genomic sequences via deep learning, thereby helping researchers a more accurate selection of fusion genes and better understand genomic breakage.

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“…There is an abundance of exceptionally long (≥ 6 repeats) STRs in the core promoter regions of human protein-coding genes, and many of these appear to be evolutionarily conserved (Ohadi, Mohammadparast, & Darvish, 2012). Microsatellites show a taxon-specific enrichment in eukaryotic genomes (Avvaru, Sharma, Verma, Mishra, & Sowpati, 2019). It is also known that transcription factor binding sites (short motifs) tend to cluster in tandem (homotypic regulatory clusters), and the repeating nature of these motifs would be expected to contribute to dependencies between positions over short ranges (Lifanov, Makeev, Nazina, & Papatsenko, 2003;Papatsenko et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Mutual information reveals a homonucleotide bias at 6 bp distance in promoters

2019

Preprint

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Background: Coding DNA in eukaryotes shows a prominent periodicity at 3-base pair (bp) because of the nonuniform use of bases at the three codon positions. This periodicity can also be interpreted as a correlation between bases at a distance of 3-bp, which in turn implies enhanced predictability at that distance as well as at integer multiples of 3 bp. This study examined possible similar dependencies between nucleotide positions in human promoter region sequences. It is possible that such noncoding sequences might show enhanced predictability at various distances other than 3 bps because of the ubiquitousness of repetitive patterns such as Short Tandem Repeats (STR). It is also possible that the 3D conformational requirements of helical DNA could induce a dependency between bps occupying certain relative positions. Mutual Information (MI), an information-theoretic quantity that can be interpreted as a measure of correlation or predictability between two sequence positions, was used to probe promoter sequences in Homo sapiens. Coding DNA sequences were also probed as a methodological control. Results:The MI measure showed a clear 3-bp signal with integer harmonics in coding DNA sequences. This shows that the MI measure is sensitive to a known repetitive signal in coding DNA sequences. MI in promoter sequences fell with increasing distance between two positions, but also showed an unexpected and significant rise at a distance of 6-bp (i.e., between the first and the seventh bases in a sequence). Harmonic intrusion of a 3-bp signal from coding DNA was ruled out as an explanation for this 6-bp signal in promoter DNA. Purposely misaligning the promoter sequences had essentially no effect on the increased correlation at a distance of 6 bp. Conclusions:Human promoter DNA sequences shows enhanced predictability (i.e., increased mutual information) between a given position and a position 6 bp downstream. This signal runs counter to the general fall in mutual information as the distance between positions increases. The increased correlation at a distance of 6 bp does not depend on the precise alignment of the sequences. Possible explanations for this enhanced predictability are discussed.

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MSDB: a comprehensive, annotated database of microsatellites

Cited by 24 publications

References 23 publications

DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats

DNA polymerase stalling at structured DNA constrains the expansion of short tandem repeats

Deep Learning Approach to Genomic Breakage Study from Primary Sequence

Mutual information reveals a homonucleotide bias at 6 bp distance in promoters

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