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A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs.

Idaghdour Y, Storey JD, Jadallah SJ, Gibson G - PLoS Genet. (2008)

Bottom Line: Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence.Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression.Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.

View Article: PubMed Central - PubMed

Affiliation: North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.

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Related in: MedlinePlus

Sex and location effects on methylation patterns.Two-way clustering of differentially methylated CpG sites at P<0.05 (ANOVA) for the sex effect (A) and for the location effect (B). Sample labels indicate their sex and location (M: male, F: female, E: nomad, SN: rural, and A: urban). There is clear separation of the sexes in (A), and a suggestion of a signature of urban living for a dozen or so genes in (B) highlighted as the Anza-enriched cluster.
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pgen-1000052-g003: Sex and location effects on methylation patterns.Two-way clustering of differentially methylated CpG sites at P<0.05 (ANOVA) for the sex effect (A) and for the location effect (B). Sample labels indicate their sex and location (M: male, F: female, E: nomad, SN: rural, and A: urban). There is clear separation of the sexes in (A), and a suggestion of a signature of urban living for a dozen or so genes in (B) highlighted as the Anza-enriched cluster.

Mentions: The observed differential expression could be due to differences in the ratios of the numerous cell types present in the total leukocyte population, to transient changes in activity of transcription factors and micro RNAs, or to longer-term epigenetic modification of chromatin structure. To test for one possible epigenetic mechanism, we measured the degree of methylation at 1,505 CpG sites [20] representing 805 genes of various classes, including tumor suppressor genes, oncogenes, genes involved in DNA repair, cell cycle control, differentiation and apoptosis. 420 of these sites were within genes included in our list of transcripts differentially expressed among locations. 58 differences in CpG site methylation between males and females were detected at a P<0.01 with a mixed model analysis of variance (Figure 3A), the majority involving X-linked genes, as expected given the correspondence of methylation with X-inactivation [21] (Figure S6), thus providing a positive control for the methodology. However, only 18 CpG sites were found to differ between regions in this analysis at the same significance level, which is no more than expected by chance. A small signature of a dozen or so genes differentiated half of the urban population (Figure 3B), but on the basis of our results epigenetic modification via methylation can only account for a small fraction of the expression divergence between regions.


A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs.

Idaghdour Y, Storey JD, Jadallah SJ, Gibson G - PLoS Genet. (2008)

Sex and location effects on methylation patterns.Two-way clustering of differentially methylated CpG sites at P<0.05 (ANOVA) for the sex effect (A) and for the location effect (B). Sample labels indicate their sex and location (M: male, F: female, E: nomad, SN: rural, and A: urban). There is clear separation of the sexes in (A), and a suggestion of a signature of urban living for a dozen or so genes in (B) highlighted as the Anza-enriched cluster.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2290968&req=5

pgen-1000052-g003: Sex and location effects on methylation patterns.Two-way clustering of differentially methylated CpG sites at P<0.05 (ANOVA) for the sex effect (A) and for the location effect (B). Sample labels indicate their sex and location (M: male, F: female, E: nomad, SN: rural, and A: urban). There is clear separation of the sexes in (A), and a suggestion of a signature of urban living for a dozen or so genes in (B) highlighted as the Anza-enriched cluster.
Mentions: The observed differential expression could be due to differences in the ratios of the numerous cell types present in the total leukocyte population, to transient changes in activity of transcription factors and micro RNAs, or to longer-term epigenetic modification of chromatin structure. To test for one possible epigenetic mechanism, we measured the degree of methylation at 1,505 CpG sites [20] representing 805 genes of various classes, including tumor suppressor genes, oncogenes, genes involved in DNA repair, cell cycle control, differentiation and apoptosis. 420 of these sites were within genes included in our list of transcripts differentially expressed among locations. 58 differences in CpG site methylation between males and females were detected at a P<0.01 with a mixed model analysis of variance (Figure 3A), the majority involving X-linked genes, as expected given the correspondence of methylation with X-inactivation [21] (Figure S6), thus providing a positive control for the methodology. However, only 18 CpG sites were found to differ between regions in this analysis at the same significance level, which is no more than expected by chance. A small signature of a dozen or so genes differentiated half of the urban population (Figure 3B), but on the basis of our results epigenetic modification via methylation can only account for a small fraction of the expression divergence between regions.

Bottom Line: Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence.Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression.Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.

View Article: PubMed Central - PubMed

Affiliation: North Carolina State University, Raleigh, North Carolina, United States of America.

ABSTRACT
The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans.

Show MeSH
Related in: MedlinePlus