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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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Related in: MedlinePlus

Sensitivity of the optimal method evaluated in silico.The plot shows the number of times in silico recombination events along the sequence were detected by IRiS depending on the breakpoint location. Different colors indicate different ways to produce the recombinant sequence, from light gray to black: “random” indicates that parental haplotypes were taken at random, “1dif near bkp” indicates that parental sequences had to be different near the breakpoint region (plus minus 10 SNPs), “ 2 dif near bkp” indicates that parental sequences had to be different near the breakpoint regions at both sides of the breakpoint, and “ unique” indicates that the parental sequences had to be different near the breakpoint region and the recombinant sequence had to be unique within the breakpoint region. Below, the recombination rate estimated by LDhat is shown, following the right axis.
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pcbi-1001010-g007: Sensitivity of the optimal method evaluated in silico.The plot shows the number of times in silico recombination events along the sequence were detected by IRiS depending on the breakpoint location. Different colors indicate different ways to produce the recombinant sequence, from light gray to black: “random” indicates that parental haplotypes were taken at random, “1dif near bkp” indicates that parental sequences had to be different near the breakpoint region (plus minus 10 SNPs), “ 2 dif near bkp” indicates that parental sequences had to be different near the breakpoint regions at both sides of the breakpoint, and “ unique” indicates that the parental sequences had to be different near the breakpoint region and the recombinant sequence had to be unique within the breakpoint region. Below, the recombination rate estimated by LDhat is shown, following the right axis.

Mentions: A study on the capacity of the optimal method to detect recent recombination events was performed through in silico recombination simulations with real sequences (same dataset as in the previous section). This allowed us to assess the characteristics that a particular recombination event should have in order to be detected by IRiS, and also to evaluate IRiS when working with real data. We performed the same analysis several times varying the process of selection of the two parental haplotypes (Figure 7).


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 evaluated in silico.The plot shows the number of times in silico recombination events along the sequence were detected by IRiS depending on the breakpoint location. Different colors indicate different ways to produce the recombinant sequence, from light gray to black: “random” indicates that parental haplotypes were taken at random, “1dif near bkp” indicates that parental sequences had to be different near the breakpoint region (plus minus 10 SNPs), “ 2 dif near bkp” indicates that parental sequences had to be different near the breakpoint regions at both sides of the breakpoint, and “ unique” indicates that the parental sequences had to be different near the breakpoint region and the recombinant sequence had to be unique within the breakpoint region. Below, the recombination rate estimated by LDhat is shown, following the right axis.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1001010-g007: Sensitivity of the optimal method evaluated in silico.The plot shows the number of times in silico recombination events along the sequence were detected by IRiS depending on the breakpoint location. Different colors indicate different ways to produce the recombinant sequence, from light gray to black: “random” indicates that parental haplotypes were taken at random, “1dif near bkp” indicates that parental sequences had to be different near the breakpoint region (plus minus 10 SNPs), “ 2 dif near bkp” indicates that parental sequences had to be different near the breakpoint regions at both sides of the breakpoint, and “ unique” indicates that the parental sequences had to be different near the breakpoint region and the recombinant sequence had to be unique within the breakpoint region. Below, the recombination rate estimated by LDhat is shown, following the right axis.
Mentions: A study on the capacity of the optimal method to detect recent recombination events was performed through in silico recombination simulations with real sequences (same dataset as in the previous section). This allowed us to assess the characteristics that a particular recombination event should have in order to be detected by IRiS, and also to evaluate IRiS when working with real data. We performed the same analysis several times varying the process of selection of the two parental haplotypes (Figure 7).

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