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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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Nucleotide and recombination diversity.Values were calculated for each of the populations based both on haplotypes and recotypes for the 18 regions. Values of recombination diversity have been multiplied by 100 to make them comparable.
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pcbi-1001010-g008: Nucleotide and recombination diversity.Values were calculated for each of the populations based both on haplotypes and recotypes for the 18 regions. Values of recombination diversity have been multiplied by 100 to make them comparable.

Mentions: A search for human X-chromosome regions harboring more than 80 SNPs and not containing known genes, copy number variants or segmental duplications (see Methods) yielded the 18 regions shown in Table S4. Overall, they span slightly more than 7 Mb, and contain 2054 SNPs that were genotyped in 537 male X chromosomes of the HapMap [14] Phase 3 project. We selected the X chromosome in males in order to avoid phasing errors that would mimic recent recombination events. We run IRiS over the 18 regions independently using the optimal method; we inferred a total of 3598 recombinations. Thus, after running IRiS in a set of haplotypes, we obtained a set of recotypes, each of them representing the recombination history of each initial chromosome with the putative position of each of the recombination events. We calculated the nucleotide diversity over the 18 regions together, and we also calculated the recombination diversity by doing the same process with the recotype data (Figure 8). Because of the ascertainment bias in SNP selection in Hap Map 3, nucleotide diversity values did not show any specific pattern at the continental level; but recombination diversity did, having a much higher diversity within African populations. This suggests that the recombinational diversity measure is not affected by the SNP ascertainment bias.


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)

Nucleotide and recombination diversity.Values were calculated for each of the populations based both on haplotypes and recotypes for the 18 regions. Values of recombination diversity have been multiplied by 100 to make them comparable.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1001010-g008: Nucleotide and recombination diversity.Values were calculated for each of the populations based both on haplotypes and recotypes for the 18 regions. Values of recombination diversity have been multiplied by 100 to make them comparable.
Mentions: A search for human X-chromosome regions harboring more than 80 SNPs and not containing known genes, copy number variants or segmental duplications (see Methods) yielded the 18 regions shown in Table S4. Overall, they span slightly more than 7 Mb, and contain 2054 SNPs that were genotyped in 537 male X chromosomes of the HapMap [14] Phase 3 project. We selected the X chromosome in males in order to avoid phasing errors that would mimic recent recombination events. We run IRiS over the 18 regions independently using the optimal method; we inferred a total of 3598 recombinations. Thus, after running IRiS in a set of haplotypes, we obtained a set of recotypes, each of them representing the recombination history of each initial chromosome with the putative position of each of the recombination events. We calculated the nucleotide diversity over the 18 regions together, and we also calculated the recombination diversity by doing the same process with the recotype data (Figure 8). Because of the ascertainment bias in SNP selection in Hap Map 3, nucleotide diversity values did not show any specific pattern at the continental level; but recombination diversity did, having a much higher diversity within African populations. This suggests that the recombinational diversity measure is not affected by the SNP ascertainment bias.

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