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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

The average cleavage intensity profile of regions surrounding germline small indels in the human genome.(a) for the entire genome. The average cleavage intensity for each position from −100 bp to +100 bp relative to indel start site was indicated by red rectangles. The blue bars represent the 95% confidence interval. (b) for individual chromosome. The average cleavage intensity profiles for the regions from −100 bp to +100 bp relative to indel start site on each human chromosome.
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f2: The average cleavage intensity profile of regions surrounding germline small indels in the human genome.(a) for the entire genome. The average cleavage intensity for each position from −100 bp to +100 bp relative to indel start site was indicated by red rectangles. The blue bars represent the 95% confidence interval. (b) for individual chromosome. The average cleavage intensity profiles for the regions from −100 bp to +100 bp relative to indel start site on each human chromosome.

Mentions: To investigate structural properties of the regions surrounding these indels, we calculated the DNA cleavage intensity of 200 bp sequences surrounding the indels, that is, −100 bp to +100 bp relative to the indel start sites (position 0) using ORChID220. The average cleavage intensity profile surrounding all the indels for the human genome is shown in Figure 2a and the one for individual chromosomes in Figure 2b (For clarity, individual chromosome's average cleavage intensity with 95% confidence interval is shown in Supplementary Figure S1). The pattern is amazingly consistent across all the chromosomes: cleavage intensity in the vicinity of indel start sites is significantly lower than other positions (Student's t-test, p<2.2 × 10−22). Similarly, the deep valley corresponding to very low cleavage intensity near indel start sites is also observed in the 16,742 human somatic indels (Figures 3a–b, Supplementary Figure S2) and the 1,439,788 mouse indels (Figures 4a–b, Supplementary Figure S3).


The pattern of DNA cleavage intensity around indels.

Chen W, Zhang L - Sci Rep (2015)

The average cleavage intensity profile of regions surrounding germline small indels in the human genome.(a) for the entire genome. The average cleavage intensity for each position from −100 bp to +100 bp relative to indel start site was indicated by red rectangles. The blue bars represent the 95% confidence interval. (b) for individual chromosome. The average cleavage intensity profiles for the regions from −100 bp to +100 bp relative to indel start site on each human chromosome.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: The average cleavage intensity profile of regions surrounding germline small indels in the human genome.(a) for the entire genome. The average cleavage intensity for each position from −100 bp to +100 bp relative to indel start site was indicated by red rectangles. The blue bars represent the 95% confidence interval. (b) for individual chromosome. The average cleavage intensity profiles for the regions from −100 bp to +100 bp relative to indel start site on each human chromosome.
Mentions: To investigate structural properties of the regions surrounding these indels, we calculated the DNA cleavage intensity of 200 bp sequences surrounding the indels, that is, −100 bp to +100 bp relative to the indel start sites (position 0) using ORChID220. The average cleavage intensity profile surrounding all the indels for the human genome is shown in Figure 2a and the one for individual chromosomes in Figure 2b (For clarity, individual chromosome's average cleavage intensity with 95% confidence interval is shown in Supplementary Figure S1). The pattern is amazingly consistent across all the chromosomes: cleavage intensity in the vicinity of indel start sites is significantly lower than other positions (Student's t-test, p<2.2 × 10−22). Similarly, the deep valley corresponding to very low cleavage intensity near indel start sites is also observed in the 16,742 human somatic indels (Figures 3a–b, Supplementary Figure S2) and the 1,439,788 mouse indels (Figures 4a–b, Supplementary Figure S3).

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