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A new method to reconstruct recombination events at a genomic scale.

Melé M, Javed A, Pybus M, Calafell F, Parida L, Bertranpetit J, Genographic Consortium Membe - PLoS Comput. Biol. (2010)

Bottom Line: Newer recombinations overwrite traces of past ones and our results indicate more recent recombinations are detected by IRiS with greater sensitivity.Principal component analysis and multidimensional scaling based on recotypes reproduced the relationships between the eleven HapMap Phase III populations that can be expected from known human population history, thus further validating IRiS.We believe that our new method will contribute to the study of the distribution of recombination events across the genomes and, for the first time, it will allow the use of recombination as genetic marker to study human genetic variation.

View Article: PubMed Central - PubMed

Affiliation: IBE, Institute of Evolutionary Biology (UPF-CSIC), CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.

ABSTRACT
Recombination is one of the main forces shaping genome diversity, but the information it generates is often overlooked. A recombination event creates a junction between two parental sequences that may be transmitted to the subsequent generations. Just like mutations, these junctions carry evidence of the shared past of the sequences. We present the IRiS algorithm, which detects past recombination events from extant sequences and specifies the place of each recombination and which are the recombinants sequences. We have validated and calibrated IRiS for the human genome using coalescent simulations replicating standard human demographic history and a variable recombination rate model, and we have fine-tuned IRiS parameters to simultaneously optimize for false discovery rate, sensitivity, and accuracy in placing the recombination events in the sequence. Newer recombinations overwrite traces of past ones and our results indicate more recent recombinations are detected by IRiS with greater sensitivity. IRiS analysis of the MS32 region, previously studied using sperm typing, showed good concordance with estimated recombination rates. We also applied IRiS to haplotypes for 18 X-chromosome regions in HapMap Phase 3 populations. Recombination events detected for each individual were recoded as binary allelic states and combined into recotypes. Principal component analysis and multidimensional scaling based on recotypes reproduced the relationships between the eleven HapMap Phase III populations that can be expected from known human population history, thus further validating IRiS. We believe that our new method will contribute to the study of the distribution of recombination events across the genomes and, for the first time, it will allow the use of recombination as genetic marker to study human genetic variation.

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Sensitivity of the optimal method to detect recombinations depending on age.Results plotted are the averaged between 100 simulations. The black curve depicts how sensitivity of IRiS varies with the age of the recombination events (in bins of 500 generations) and follows the left axis. The two gray curves represent the number of recombination events generated by COSI and detected by IRiS and follow the right axis.
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pcbi-1001010-g005: Sensitivity of the optimal method to detect recombinations depending on age.Results plotted are the averaged between 100 simulations. The black curve depicts how sensitivity of IRiS varies with the age of the recombination events (in bins of 500 generations) and follows the left axis. The two gray curves represent the number of recombination events generated by COSI and detected by IRiS and follow the right axis.

Mentions: We also studied the effect of the age of the recombination events on false discovery rate and sensitivity. When looking across parameter sets, the methods with lowest false discovery rates tended to detect most recent recombination events as average (Figure S4). It is important to highlight that evidence of older recombinations is overwritten by newer ones and hence they leave their trace in relatively shorter segments requiring smaller grain size to be detected which, at the same time, tend to have a higher false discovery rate (Figure S1D). We also calculated the sensitivity of IRiS along time in bins of 500 generations for 100 COSI simulations (Figure 5) using the optimal method. Results show that sensitivity increases with time from past to present going up to 45% for recombination events having occurred in the past 500 generations.


A new method to reconstruct recombination events at a genomic scale.

Melé M, Javed A, Pybus M, Calafell F, Parida L, Bertranpetit J, Genographic Consortium Membe - PLoS Comput. Biol. (2010)

Sensitivity of the optimal method to detect recombinations depending on age.Results plotted are the averaged between 100 simulations. The black curve depicts how sensitivity of IRiS varies with the age of the recombination events (in bins of 500 generations) and follows the left axis. The two gray curves represent the number of recombination events generated by COSI and detected by IRiS and follow the right axis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991245&req=5

pcbi-1001010-g005: Sensitivity of the optimal method to detect recombinations depending on age.Results plotted are the averaged between 100 simulations. The black curve depicts how sensitivity of IRiS varies with the age of the recombination events (in bins of 500 generations) and follows the left axis. The two gray curves represent the number of recombination events generated by COSI and detected by IRiS and follow the right axis.
Mentions: We also studied the effect of the age of the recombination events on false discovery rate and sensitivity. When looking across parameter sets, the methods with lowest false discovery rates tended to detect most recent recombination events as average (Figure S4). It is important to highlight that evidence of older recombinations is overwritten by newer ones and hence they leave their trace in relatively shorter segments requiring smaller grain size to be detected which, at the same time, tend to have a higher false discovery rate (Figure S1D). We also calculated the sensitivity of IRiS along time in bins of 500 generations for 100 COSI simulations (Figure 5) using the optimal method. Results show that sensitivity increases with time from past to present going up to 45% for recombination events having occurred in the past 500 generations.

Bottom Line: Newer recombinations overwrite traces of past ones and our results indicate more recent recombinations are detected by IRiS with greater sensitivity.Principal component analysis and multidimensional scaling based on recotypes reproduced the relationships between the eleven HapMap Phase III populations that can be expected from known human population history, thus further validating IRiS.We believe that our new method will contribute to the study of the distribution of recombination events across the genomes and, for the first time, it will allow the use of recombination as genetic marker to study human genetic variation.

View Article: PubMed Central - PubMed

Affiliation: IBE, Institute of Evolutionary Biology (UPF-CSIC), CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.

ABSTRACT
Recombination is one of the main forces shaping genome diversity, but the information it generates is often overlooked. A recombination event creates a junction between two parental sequences that may be transmitted to the subsequent generations. Just like mutations, these junctions carry evidence of the shared past of the sequences. We present the IRiS algorithm, which detects past recombination events from extant sequences and specifies the place of each recombination and which are the recombinants sequences. We have validated and calibrated IRiS for the human genome using coalescent simulations replicating standard human demographic history and a variable recombination rate model, and we have fine-tuned IRiS parameters to simultaneously optimize for false discovery rate, sensitivity, and accuracy in placing the recombination events in the sequence. Newer recombinations overwrite traces of past ones and our results indicate more recent recombinations are detected by IRiS with greater sensitivity. IRiS analysis of the MS32 region, previously studied using sperm typing, showed good concordance with estimated recombination rates. We also applied IRiS to haplotypes for 18 X-chromosome regions in HapMap Phase 3 populations. Recombination events detected for each individual were recoded as binary allelic states and combined into recotypes. Principal component analysis and multidimensional scaling based on recotypes reproduced the relationships between the eleven HapMap Phase III populations that can be expected from known human population history, thus further validating IRiS. We believe that our new method will contribute to the study of the distribution of recombination events across the genomes and, for the first time, it will allow the use of recombination as genetic marker to study human genetic variation.

Show MeSH
Related in: MedlinePlus