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Recurring genomic breaks in independent lineages support genomic fragility.

Hinsch H, Hannenhalli S - BMC Evol. Biol. (2006)

Bottom Line: We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages.Furthermore, the fragile regions are enriched for segmental duplications.Based on a novel methodology, our work provides additional support for the existence of fragile regions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA, USA. hhinsch@yahoo.com <hhinsch@yahoo.com>

ABSTRACT

Background: Recent findings indicate that evolutionary breaks in the genome are not randomly distributed, and that certain regions, so-called fragile regions, are predisposed to breakages. Previous approaches to the study of genomic fragility have examined the distribution of breaks, as well as the coincidence of breaks with segmental duplications and repeats, within a single species. In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages.

Results: We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages. Our investigation, based on Human, Chimp, Mouse, Rat, Dog and Chicken, suggests that the propensity of a chromosomal region to break is significantly correlated among independent lineages, even when covariates are considered. Furthermore, the fragile regions are enriched for segmental duplications.

Conclusion: Based on a novel methodology, our work provides additional support for the existence of fragile regions.

Show MeSH
Illustration of 'joint breaks' in the FBP and FBR schemes. Distinct markers are identified by their shape and size. (a) FBP: Markers (x1 x2 x3 x4) occur in the specified order and consecutively in both of the 'fixed' species. In both 'variable' species, the flanks (x1 x2) and (x3 x4) are consecutive but the region between markers x2 and x3 is disrupted (contains additional markers). (b) FBR: Markers (x1 x2 x3 x4 x5) occur in the specified order and consecutively in both of the 'fixed' species. In the variable species 1 the flanks (x2 x3) and (x4 x5) remain unbroken, while in variable species 2 the flanks (x1 x2) and (x3 x4) remain unbroken, but in both variable species the entire block of 5 markers is disrupted. This situation will be identified as a joint break according to FBR but not according to FBP. FBP is a special case of FBR.
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Figure 2: Illustration of 'joint breaks' in the FBP and FBR schemes. Distinct markers are identified by their shape and size. (a) FBP: Markers (x1 x2 x3 x4) occur in the specified order and consecutively in both of the 'fixed' species. In both 'variable' species, the flanks (x1 x2) and (x3 x4) are consecutive but the region between markers x2 and x3 is disrupted (contains additional markers). (b) FBR: Markers (x1 x2 x3 x4 x5) occur in the specified order and consecutively in both of the 'fixed' species. In the variable species 1 the flanks (x2 x3) and (x4 x5) remain unbroken, while in variable species 2 the flanks (x1 x2) and (x3 x4) remain unbroken, but in both variable species the entire block of 5 markers is disrupted. This situation will be identified as a joint break according to FBR but not according to FBP. FBP is a special case of FBR.

Mentions: Here we analyze the region between a pair of adjacent markers. We search for say, 4 markers (x1 x2 x3 x4) that occur in the specified order and consecutively in both of the 'fixed' species. For each of the variable species V, we define the breakpoint region between markers x2 and x3 to be 'broken' if both (x1 x2) and (x3 x4) are consecutive in V but markers x2 and x3 are not consecutive in V (see Figure 2). Note the requirement for consecutive markers on either side of the breakpoint. This is meant to make the analysis more robust against noise. The parameter 'minimum flank' is the number of required consecutive markers on each side. We have used two values – 2 or 3.


Recurring genomic breaks in independent lineages support genomic fragility.

Hinsch H, Hannenhalli S - BMC Evol. Biol. (2006)

Illustration of 'joint breaks' in the FBP and FBR schemes. Distinct markers are identified by their shape and size. (a) FBP: Markers (x1 x2 x3 x4) occur in the specified order and consecutively in both of the 'fixed' species. In both 'variable' species, the flanks (x1 x2) and (x3 x4) are consecutive but the region between markers x2 and x3 is disrupted (contains additional markers). (b) FBR: Markers (x1 x2 x3 x4 x5) occur in the specified order and consecutively in both of the 'fixed' species. In the variable species 1 the flanks (x2 x3) and (x4 x5) remain unbroken, while in variable species 2 the flanks (x1 x2) and (x3 x4) remain unbroken, but in both variable species the entire block of 5 markers is disrupted. This situation will be identified as a joint break according to FBR but not according to FBP. FBP is a special case of FBR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1636669&req=5

Figure 2: Illustration of 'joint breaks' in the FBP and FBR schemes. Distinct markers are identified by their shape and size. (a) FBP: Markers (x1 x2 x3 x4) occur in the specified order and consecutively in both of the 'fixed' species. In both 'variable' species, the flanks (x1 x2) and (x3 x4) are consecutive but the region between markers x2 and x3 is disrupted (contains additional markers). (b) FBR: Markers (x1 x2 x3 x4 x5) occur in the specified order and consecutively in both of the 'fixed' species. In the variable species 1 the flanks (x2 x3) and (x4 x5) remain unbroken, while in variable species 2 the flanks (x1 x2) and (x3 x4) remain unbroken, but in both variable species the entire block of 5 markers is disrupted. This situation will be identified as a joint break according to FBR but not according to FBP. FBP is a special case of FBR.
Mentions: Here we analyze the region between a pair of adjacent markers. We search for say, 4 markers (x1 x2 x3 x4) that occur in the specified order and consecutively in both of the 'fixed' species. For each of the variable species V, we define the breakpoint region between markers x2 and x3 to be 'broken' if both (x1 x2) and (x3 x4) are consecutive in V but markers x2 and x3 are not consecutive in V (see Figure 2). Note the requirement for consecutive markers on either side of the breakpoint. This is meant to make the analysis more robust against noise. The parameter 'minimum flank' is the number of required consecutive markers on each side. We have used two values – 2 or 3.

Bottom Line: We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages.Furthermore, the fragile regions are enriched for segmental duplications.Based on a novel methodology, our work provides additional support for the existence of fragile regions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA, USA. hhinsch@yahoo.com <hhinsch@yahoo.com>

ABSTRACT

Background: Recent findings indicate that evolutionary breaks in the genome are not randomly distributed, and that certain regions, so-called fragile regions, are predisposed to breakages. Previous approaches to the study of genomic fragility have examined the distribution of breaks, as well as the coincidence of breaks with segmental duplications and repeats, within a single species. In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages.

Results: We do this by quantifying the extent to which certain genomic regions are disrupted repeatedly in independent lineages. Our investigation, based on Human, Chimp, Mouse, Rat, Dog and Chicken, suggests that the propensity of a chromosomal region to break is significantly correlated among independent lineages, even when covariates are considered. Furthermore, the fragile regions are enriched for segmental duplications.

Conclusion: Based on a novel methodology, our work provides additional support for the existence of fragile regions.

Show MeSH