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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 regions surrounding the start and end site of large indels.(a) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (top left panel) and end (top right panel) site of the large indels in the human genome. (b) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (bottom left panel) and end (bottom right panel) site of the large indels in the chimpanzee genome.
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f5: Cleavage intensity for regions surrounding the start and end site of large indels.(a) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (top left panel) and end (top right panel) site of the large indels in the human genome. (b) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (bottom left panel) and end (bottom right panel) site of the large indels in the chimpanzee genome.

Mentions: We next analyzed structural properties of the regions surrounding these large indels in both human and chimpanzee genomes by calculating DNA cleavage intensity. The average cleavage intensity profiles for the positions from −100 bp to +100 bp relative to the start and end sites of the large indels in both human and chimpanzee genomes are shown in Figure 5. Similar to the pattern shown by small indels, cleavage intensities near the start and end sites of large indels were also significantly lower than other positions (t-test, p<1.7 × 10−22). However, large indels have their own distinct pattern of cleavage intensity as compared to that of small indels. Two valleys located at about +3 bp and +18 bp downstream of the start site were observed. Moreover, two valleys located at about −14 bp and −1 bp upstream of the end site of the large indels were also observed in both human (Figure 5a) and chimpanzee genomes (Figure 5b).


The pattern of DNA cleavage intensity around indels.

Chen W, Zhang L - Sci Rep (2015)

Cleavage intensity for regions surrounding the start and end site of large indels.(a) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (top left panel) and end (top right panel) site of the large indels in the human genome. (b) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (bottom left panel) and end (bottom right panel) site of the large indels in the chimpanzee genome.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Cleavage intensity for regions surrounding the start and end site of large indels.(a) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (top left panel) and end (top right panel) site of the large indels in the human genome. (b) The average cleavage intensity profile for the positions from −100 bp to +100 bp relative to the start (bottom left panel) and end (bottom right panel) site of the large indels in the chimpanzee genome.
Mentions: We next analyzed structural properties of the regions surrounding these large indels in both human and chimpanzee genomes by calculating DNA cleavage intensity. The average cleavage intensity profiles for the positions from −100 bp to +100 bp relative to the start and end sites of the large indels in both human and chimpanzee genomes are shown in Figure 5. Similar to the pattern shown by small indels, cleavage intensities near the start and end sites of large indels were also significantly lower than other positions (t-test, p<1.7 × 10−22). However, large indels have their own distinct pattern of cleavage intensity as compared to that of small indels. Two valleys located at about +3 bp and +18 bp downstream of the start site were observed. Moreover, two valleys located at about −14 bp and −1 bp upstream of the end site of the large indels were also observed in both human (Figure 5a) and chimpanzee genomes (Figure 5b).

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