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Identification of copy number variants defining genomic differences among major human groups.

Armengol L, Villatoro S, González JR, Pantano L, García-Aragonés M, Rabionet R, Cáceres M, Estivill X - PLoS ONE (2009)

Bottom Line: We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other.Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space) within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs) translate into gene-expression differences among populations, suggesting that they could have functional consequences.Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

View Article: PubMed Central - PubMed

Affiliation: Genetic Causes of Disease Group, Genes and Disease Program, Center for Genomic Regulation (CRG-UPF) and CIBERESP, Barcelona, Catalonia, Spain.

ABSTRACT

Background: Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations.

Methodology/principal findings: We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH) in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space) within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs) translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level.

Conclusions: Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

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Principal component analysis of MLPA data in HapMap populations.We decomposed the genetic variation within MLPA-estimated copy number into the first two principal axes [56], plotted each data point, and colored them according to the population of origin. Thirty percent of the total variance is explained by the two first principal components (PC1 16,62%, and PC2 13,38%), and it is evident that the first principal component discriminates variation inherent to the population of African ancestry (YRI), while the second component differentiates the populations of European (CEU) and Asian (ASN) ancestries.
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pone-0007230-g002: Principal component analysis of MLPA data in HapMap populations.We decomposed the genetic variation within MLPA-estimated copy number into the first two principal axes [56], plotted each data point, and colored them according to the population of origin. Thirty percent of the total variance is explained by the two first principal components (PC1 16,62%, and PC2 13,38%), and it is evident that the first principal component discriminates variation inherent to the population of African ancestry (YRI), while the second component differentiates the populations of European (CEU) and Asian (ASN) ancestries.

Mentions: To test for the existence of population stratification based on CNVs, we took advantage of the MLPA data generated for all analyzed loci to perform an a priori principal component analysis of the copy number information estimated for each individual [56]. We estimated that thirty percent of total variance is explained by the two principal components (PC1 16,62%, and PC2 13,38%) and we observed that using these two axes the majority of individuals consistently cluster according to their population of origin, thus supporting the idea that the three human groups are characterized by a markedly different composition of the identified CNV regions (Figure 2).


Identification of copy number variants defining genomic differences among major human groups.

Armengol L, Villatoro S, González JR, Pantano L, García-Aragonés M, Rabionet R, Cáceres M, Estivill X - PLoS ONE (2009)

Principal component analysis of MLPA data in HapMap populations.We decomposed the genetic variation within MLPA-estimated copy number into the first two principal axes [56], plotted each data point, and colored them according to the population of origin. Thirty percent of the total variance is explained by the two first principal components (PC1 16,62%, and PC2 13,38%), and it is evident that the first principal component discriminates variation inherent to the population of African ancestry (YRI), while the second component differentiates the populations of European (CEU) and Asian (ASN) ancestries.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747275&req=5

pone-0007230-g002: Principal component analysis of MLPA data in HapMap populations.We decomposed the genetic variation within MLPA-estimated copy number into the first two principal axes [56], plotted each data point, and colored them according to the population of origin. Thirty percent of the total variance is explained by the two first principal components (PC1 16,62%, and PC2 13,38%), and it is evident that the first principal component discriminates variation inherent to the population of African ancestry (YRI), while the second component differentiates the populations of European (CEU) and Asian (ASN) ancestries.
Mentions: To test for the existence of population stratification based on CNVs, we took advantage of the MLPA data generated for all analyzed loci to perform an a priori principal component analysis of the copy number information estimated for each individual [56]. We estimated that thirty percent of total variance is explained by the two principal components (PC1 16,62%, and PC2 13,38%) and we observed that using these two axes the majority of individuals consistently cluster according to their population of origin, thus supporting the idea that the three human groups are characterized by a markedly different composition of the identified CNV regions (Figure 2).

Bottom Line: We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other.Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space) within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs) translate into gene-expression differences among populations, suggesting that they could have functional consequences.Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

View Article: PubMed Central - PubMed

Affiliation: Genetic Causes of Disease Group, Genes and Disease Program, Center for Genomic Regulation (CRG-UPF) and CIBERESP, Barcelona, Catalonia, Spain.

ABSTRACT

Background: Understanding the genetic contribution to phenotype variation of human groups is necessary to elucidate differences in disease predisposition and response to pharmaceutical treatments in different human populations.

Methodology/principal findings: We have investigated the genome-wide profile of structural variation on pooled samples from the three populations studied in the HapMap project by comparative genome hybridization (CGH) in different array platforms. We have identified and experimentally validated 33 genomic loci that show significant copy number differences from one population to the other. Interestingly, we found an enrichment of genes related to environment adaptation (immune response, lipid metabolism and extracellular space) within these regions and the study of expression data revealed that more than half of the copy number variants (CNVs) translate into gene-expression differences among populations, suggesting that they could have functional consequences. In addition, the identification of single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium with the copy number alleles allowed us to detect evidences of population differentiation and recent selection at the nucleotide variation level.

Conclusions: Overall, our results provide a comprehensive view of relevant copy number changes that might play a role in phenotypic differences among major human populations, and generate a list of interesting candidates for future studies.

Show MeSH