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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
A plot of the fraction of species combinations showing significance of correlated breaks (Y-axis) against the threshold for number of breaks in the variable species (X-axis). This is based on the 6 species analysis. The same trend follows in other analyses as well. As we consider combinations with more breaks in the variable species, the fraction that show significance grows steadily. (a) FBP, (b) FBR. The numeric label on each bar indicates the number of combinations that are above the threshold.
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Figure 3: A plot of the fraction of species combinations showing significance of correlated breaks (Y-axis) against the threshold for number of breaks in the variable species (X-axis). This is based on the 6 species analysis. The same trend follows in other analyses as well. As we consider combinations with more breaks in the variable species, the fraction that show significance grows steadily. (a) FBP, (b) FBR. The numeric label on each bar indicates the number of combinations that are above the threshold.

Mentions: First, the fraction of significant combinations increases with the number of breaks in the variable species. To highlight this, we applied an increasing threshold for the minimum number of breaks in a variable species and for each such threshold we determined the fraction of significant combinations. Figure 3 shows this. For instance, when we require that the variable species have at least 200 breaks each, the fraction of significant combinations in FBP and FBR are 87% and 91% respectively.


Recurring genomic breaks in independent lineages support genomic fragility.

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

A plot of the fraction of species combinations showing significance of correlated breaks (Y-axis) against the threshold for number of breaks in the variable species (X-axis). This is based on the 6 species analysis. The same trend follows in other analyses as well. As we consider combinations with more breaks in the variable species, the fraction that show significance grows steadily. (a) FBP, (b) FBR. The numeric label on each bar indicates the number of combinations that are above the threshold.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: A plot of the fraction of species combinations showing significance of correlated breaks (Y-axis) against the threshold for number of breaks in the variable species (X-axis). This is based on the 6 species analysis. The same trend follows in other analyses as well. As we consider combinations with more breaks in the variable species, the fraction that show significance grows steadily. (a) FBP, (b) FBR. The numeric label on each bar indicates the number of combinations that are above the threshold.
Mentions: First, the fraction of significant combinations increases with the number of breaks in the variable species. To highlight this, we applied an increasing threshold for the minimum number of breaks in a variable species and for each such threshold we determined the fraction of significant combinations. Figure 3 shows this. For instance, when we require that the variable species have at least 200 breaks each, the fraction of significant combinations in FBP and FBR are 87% and 91% respectively.

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