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Genetic crossovers are predicted accurately by the computed human recombination map.

Khil PP, Camerini-Otero RD - PLoS Genet. (2010)

Bottom Line: This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers.To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees.An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations.

View Article: PubMed Central - PubMed

Affiliation: Genetics and Biochemistry Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers.

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Related in: MedlinePlus

A substantial fraction of present-day crossovers is not predicted by historic recombination rate profiles.(A) Examples of small present day crossover intervals that do not overlap historic hotspots. (B,C) Percentage of present-day crossovers in CEPH families not predicted by overlapping hotspots. The percentages of crossovers that do not overlap CEU and LDHot hotspots were calculated for several subsets of all crossovers defined with various degrees of accuracy. For comparison, the same percentage was calculated for crossovers distributed according to probabilities determined by population-averaged (B) and CEU (C) recombination rate maps. Mean and 95% CI are plotted on the graph. A large fraction of crossovers is not predicted by hotspots.
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pgen-1000831-g001: A substantial fraction of present-day crossovers is not predicted by historic recombination rate profiles.(A) Examples of small present day crossover intervals that do not overlap historic hotspots. (B,C) Percentage of present-day crossovers in CEPH families not predicted by overlapping hotspots. The percentages of crossovers that do not overlap CEU and LDHot hotspots were calculated for several subsets of all crossovers defined with various degrees of accuracy. For comparison, the same percentage was calculated for crossovers distributed according to probabilities determined by population-averaged (B) and CEU (C) recombination rate maps. Mean and 95% CI are plotted on the graph. A large fraction of crossovers is not predicted by hotspots.

Mentions: First we asked how well hotspots predict CEPH crossovers. Since the average size of crossover-containing intervals is comparable with the distance between hotspots, some crossover intervals overlap hotspots due to our inability to map them precisely. To address this issue we analyzed separately three subsets of crossovers mapped to intervals of different size (Figure 1). Smaller crossover intervals are less likely to overlap hotspots by chance (Figure S4).


Genetic crossovers are predicted accurately by the computed human recombination map.

Khil PP, Camerini-Otero RD - PLoS Genet. (2010)

A substantial fraction of present-day crossovers is not predicted by historic recombination rate profiles.(A) Examples of small present day crossover intervals that do not overlap historic hotspots. (B,C) Percentage of present-day crossovers in CEPH families not predicted by overlapping hotspots. The percentages of crossovers that do not overlap CEU and LDHot hotspots were calculated for several subsets of all crossovers defined with various degrees of accuracy. For comparison, the same percentage was calculated for crossovers distributed according to probabilities determined by population-averaged (B) and CEU (C) recombination rate maps. Mean and 95% CI are plotted on the graph. A large fraction of crossovers is not predicted by hotspots.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2813264&req=5

pgen-1000831-g001: A substantial fraction of present-day crossovers is not predicted by historic recombination rate profiles.(A) Examples of small present day crossover intervals that do not overlap historic hotspots. (B,C) Percentage of present-day crossovers in CEPH families not predicted by overlapping hotspots. The percentages of crossovers that do not overlap CEU and LDHot hotspots were calculated for several subsets of all crossovers defined with various degrees of accuracy. For comparison, the same percentage was calculated for crossovers distributed according to probabilities determined by population-averaged (B) and CEU (C) recombination rate maps. Mean and 95% CI are plotted on the graph. A large fraction of crossovers is not predicted by hotspots.
Mentions: First we asked how well hotspots predict CEPH crossovers. Since the average size of crossover-containing intervals is comparable with the distance between hotspots, some crossover intervals overlap hotspots due to our inability to map them precisely. To address this issue we analyzed separately three subsets of crossovers mapped to intervals of different size (Figure 1). Smaller crossover intervals are less likely to overlap hotspots by chance (Figure S4).

Bottom Line: This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers.To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees.An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations.

View Article: PubMed Central - PubMed

Affiliation: Genetics and Biochemistry Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers.

Show MeSH
Related in: MedlinePlus