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Environmental effects on gene expression phenotype have regional biases in the human genome.

ABSTRACT: Phenotypic discordance between monozygotic twins, such as a difference in disease susceptibility, implicates the role of the environment in determining phenotype. To assess genomewide environmental effects on "gene expression phenotype," we employed a published microarray data set for twins. We found that variations in expression phenotypes between monozygotic twins have biases in their chromosomal locations. They also showed a strong inverse correlation with gene density. Genomic regions of low gene density were environmentally sensitive, containing genes involved in response to external signals, cell differentiation, and development, etc. Genetic factors were found to make no contribution to the observed regional biases, stressing the role of epigenetics. We propose that epigenetic modifications might occur more frequently in heterochromatic, gene-poor regions in response to environmental signals while gene-rich regions tend to remain in an active chromatin configuration for the constitutive expression of underlying genes.

SUBMITTER: Choi JK

PROVIDER: S-EPMC1855137 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Environmental effects on gene expression phenotype have regional biases in the human genome.

Choi Jung Kyoon JK Kim Sang Cheol SC

Genetics 20070121 4

Phenotypic discordance between monozygotic twins, such as a difference in disease susceptibility, implicates the role of the environment in determining phenotype. To assess genomewide environmental effects on "gene expression phenotype," we employed a published microarray data set for twins. We found that variations in expression phenotypes between monozygotic twins have biases in their chromosomal locations. They also showed a strong inverse correlation with gene density. Genomic regions of low ...[more]

PMID: 17237506

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Project description:BackgroundAccumulation of visceral adipose tissue (VAT) is clearly associated with an increased risk of obesity-related diseases and all-cause mortality, whereas gluteal subcutaneous fat accumulation (g-SAT) is associated with a lower risk. The relative contribution, in term of cardiovascular risk, of abdominal subcutaneous adipose tissue (a-SAT) is still controversial with studies showing both a detrimental effect and a protective role. Animal and in vitro studies demonstrated that adipocytes from visceral and subcutaneous depots have distinct morphological, metabolic and functional characteristics. These regional differences have a key role in the pathogenesis of obesity-related diseases. There is recent evidence that differentiation between upper-body and lower-body adipose tissues might be under control of site-specific sets of developmental genes, such as Homebox (HOX) genes, a group of related genes that control the body plan of an embryo along the anterior-posterior axis. However, the possible heterogeneity between different subcutaneous regions has not been extensively investigated. Here we studied global mRNA expression in g-SAT and a-SAT with a microarray approach. RNA was isolated from g-SAT and a-SAT biopsy, from eight healthy subjects, and hybridized on RNA microarray chips in order to detect regional differences in gene expression.ResultsA total of 131 genes are significantly and differently (>1.5 fold change, p < 0.05) expressed in a-SAT and g-SAT. Expression profiling reveals significant differences in expression of several HOX genes. Interestingly, two molecular signature of visceral adipocyte lineage, homebox genes HOXA5 and NR2F1, are up-regulated in a-SAT versus g-SAT by a 2.5 fold change.ConclusionsOur study shows that g-SAT and a-SAT have distinct expression profiles. The finding of a different expression of HOX genes, fundamental during the embryo development, suggests an early regional differentiation of subcutaneous adipose depots. Moreover, the higher expression of HOXA5 and NR2F1, two molecular signatures of visceral adipocytes, in a-SAT suggests that this subcutaneous adipose depot could be more similar to VAT than g-SAT. Our data suggest that we should look at SAT as composed of distinct depots with possibly different impact in obesity associated metabolic complications.

Project description:Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.

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Environmental effects on gene expression phenotype have regional biases in the human genome.

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Environmental effects on gene expression phenotype have regional biases in the human genome.

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