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The pattern of DNA cleavage intensity around indels.

Chen W, Zhang L - Sci Rep (2015)

Bottom Line: Compared to small indels, the patterns of DNA cleavage intensity around large indels are more complex, and there are two low intensity regions near each end of the indels that are approximately 13 bp apart from each other.Detailed analyses of a subset of indels show that there is slight difference in cleavage intensity distribution between insertion indels and deletion indels that could be contributed by their respective enrichment of different repetitive elements.These results will provide new insight into indel generation mechanisms.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Physics, School of Sciences, Center for Genomics and Computational Biology, Hebei United University, Tangshan, China 063000 [2] Department of Computer Science, Virginia Tech, Blacksburg VA 24060.

ABSTRACT
Indels (insertions and deletions) are the second most common form of genetic variations in the eukaryotic genomes and are responsible for a multitude of genetic diseases. Despite its significance, detailed molecular mechanisms for indel generation are still unclear. Here we examined 2,656,597 small human and mouse germline indels, 16,742 human somatic indels, 10,599 large human insertions, and 5,822 large chimpanzee insertions and systematically analyzed the patterns of DNA cleavage intensities in the 200 base pair regions surrounding these indels. Our results show that DNA cleavage intensities close to the start and end points of indels are significantly lower than other regions, for both small human germline and somatic indels and also for mouse small indels. Compared to small indels, the patterns of DNA cleavage intensity around large indels are more complex, and there are two low intensity regions near each end of the indels that are approximately 13 bp apart from each other. Detailed analyses of a subset of indels show that there is slight difference in cleavage intensity distribution between insertion indels and deletion indels that could be contributed by their respective enrichment of different repetitive elements. These results will provide new insight into indel generation mechanisms.

No MeSH data available.


Related in: MedlinePlus

Cleavage intensity for random genomic positions in the human genome.The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to random genomic positions.
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f7: Cleavage intensity for random genomic positions in the human genome.The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to random genomic positions.

Mentions: As a control analysis, we randomly sampled 17,000 human SNPs from UCSC genome database (hg19/snp138) and analyzed the cleavage intensity of surrounding sequences (from −100 to +100 bps). The average cleavage intensity profile of SNPs is shown in Figure 6. In contrast to indels, the cleavage intensity of SNP site is significantly higher than surrounding regions. Furthermore, we also randomly picked out 10,000 genomic positions and calculated the cleavage intensity for their surrounding sequences (from −100 to +100 bps). Figure 7 shows that the average cleavage intensity of random genomic regions exhibits random fluctuations and has no strong distribution pattern as compared to the selected sites, and therefore is dramatically different from that of indel regions and SNP regions (Figures 2,3,4,5). Taken together, these results ruled out the possibility that the observed lower cleavage intensity near start or end site of indels is due to sequence bias.


The pattern of DNA cleavage intensity around indels.

Chen W, Zhang L - Sci Rep (2015)

Cleavage intensity for random genomic positions in the human genome.The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to random genomic positions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321175&req=5

f7: Cleavage intensity for random genomic positions in the human genome.The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to random genomic positions.
Mentions: As a control analysis, we randomly sampled 17,000 human SNPs from UCSC genome database (hg19/snp138) and analyzed the cleavage intensity of surrounding sequences (from −100 to +100 bps). The average cleavage intensity profile of SNPs is shown in Figure 6. In contrast to indels, the cleavage intensity of SNP site is significantly higher than surrounding regions. Furthermore, we also randomly picked out 10,000 genomic positions and calculated the cleavage intensity for their surrounding sequences (from −100 to +100 bps). Figure 7 shows that the average cleavage intensity of random genomic regions exhibits random fluctuations and has no strong distribution pattern as compared to the selected sites, and therefore is dramatically different from that of indel regions and SNP regions (Figures 2,3,4,5). Taken together, these results ruled out the possibility that the observed lower cleavage intensity near start or end site of indels is due to sequence bias.

Bottom Line: Compared to small indels, the patterns of DNA cleavage intensity around large indels are more complex, and there are two low intensity regions near each end of the indels that are approximately 13 bp apart from each other.Detailed analyses of a subset of indels show that there is slight difference in cleavage intensity distribution between insertion indels and deletion indels that could be contributed by their respective enrichment of different repetitive elements.These results will provide new insight into indel generation mechanisms.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Physics, School of Sciences, Center for Genomics and Computational Biology, Hebei United University, Tangshan, China 063000 [2] Department of Computer Science, Virginia Tech, Blacksburg VA 24060.

ABSTRACT
Indels (insertions and deletions) are the second most common form of genetic variations in the eukaryotic genomes and are responsible for a multitude of genetic diseases. Despite its significance, detailed molecular mechanisms for indel generation are still unclear. Here we examined 2,656,597 small human and mouse germline indels, 16,742 human somatic indels, 10,599 large human insertions, and 5,822 large chimpanzee insertions and systematically analyzed the patterns of DNA cleavage intensities in the 200 base pair regions surrounding these indels. Our results show that DNA cleavage intensities close to the start and end points of indels are significantly lower than other regions, for both small human germline and somatic indels and also for mouse small indels. Compared to small indels, the patterns of DNA cleavage intensity around large indels are more complex, and there are two low intensity regions near each end of the indels that are approximately 13 bp apart from each other. Detailed analyses of a subset of indels show that there is slight difference in cleavage intensity distribution between insertion indels and deletion indels that could be contributed by their respective enrichment of different repetitive elements. These results will provide new insight into indel generation mechanisms.

No MeSH data available.


Related in: MedlinePlus