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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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First and second components of the Principal Components Analysis.Only recombinations present in at least in two individuals were taken for the analysis. The first component explained 18.03% of the variance and the second component 14.53%.
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pcbi-1001010-g009: First and second components of the Principal Components Analysis.Only recombinations present in at least in two individuals were taken for the analysis. The first component explained 18.03% of the variance and the second component 14.53%.

Mentions: We next analyzed the geographical structure of recombination events by means of two different statistical analyses: Principal Component Analysis (PCA) and Multidimensional Scaling (MDS). Results of the PCA analysis for component 1 and 2 can be seen in Figure 9. The first component separates African from non–African populations, with the African-Americans in an intermediate position. The second component separates European from East Asian populations leaving the Mexican in between them and the South Asians closer to the Europeans. Interestingly, the second component also separates Western Africans (Yoruba) and African-Americans, from the Eastern Africans (Maasai and Luhya).


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)

First and second components of the Principal Components Analysis.Only recombinations present in at least in two individuals were taken for the analysis. The first component explained 18.03% of the variance and the second component 14.53%.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1001010-g009: First and second components of the Principal Components Analysis.Only recombinations present in at least in two individuals were taken for the analysis. The first component explained 18.03% of the variance and the second component 14.53%.
Mentions: We next analyzed the geographical structure of recombination events by means of two different statistical analyses: Principal Component Analysis (PCA) and Multidimensional Scaling (MDS). Results of the PCA analysis for component 1 and 2 can be seen in Figure 9. The first component separates African from non–African populations, with the African-Americans in an intermediate position. The second component separates European from East Asian populations leaving the Mexican in between them and the South Asians closer to the Europeans. Interestingly, the second component also separates Western Africans (Yoruba) and African-Americans, from the Eastern Africans (Maasai and Luhya).

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