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Orientation, distance, regulation and function of neighbouring genes.

Gherman A, Wang R, Avramopoulos D - Hum. Genomics (2009)

Bottom Line: The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes.We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome.We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution.

View Article: PubMed Central - HTML - PubMed

Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

ABSTRACT
The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes. There are multiple lines of evidence that this arrangement is not random, both in terms of intergenic distances and orientation of neighbouring genes. We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome. We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution. In addition to confirming and extending known properties of the genome, such as the significance of gene deserts and the importance of 'head to head' orientation of gene pairs in proximity, we provide significant new observations that include a smaller average size for intervals separating the 3' ends of neighbouring genes, a correlation of gene expression across tissues for genes as far as 100 kilobases apart and signatures of increasing positive selection with decreasing interval size surprisingly relaxing for intervals smaller than approximately 500 base pairs. Further, we provide extensive graphical representations of the genome-wide data to allow for observations and comparisons beyond what we address.

Show MeSH
Gene Ontology clusters. The fraction of gene pairs with membership in common in biological proces clusters for the three types of gene pairs and according to distance. The sliding average approach used in Figure 3 is also applied here. The random expectation is shown with a dashed red line. Abbreviation: GO, gene ontology.
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Figure 5: Gene Ontology clusters. The fraction of gene pairs with membership in common in biological proces clusters for the three types of gene pairs and according to distance. The sliding average approach used in Figure 3 is also applied here. The random expectation is shown with a dashed red line. Abbreviation: GO, gene ontology.

Mentions: Joint membership of neighbouring genes in functional clusters based on biological processes in the GO database was observed more frequently than expected by chance for all three categories of neighbours and for all distances between adjacent genes (Figure 5). TT and HH genes showed the same increased functional relatedness with each other across all interval sizes. TH genes showed the same increase at distances > 100 kb but significantly greater relatedness at smaller distances. Very similar results were obtained using clusters based on the KEGG pathways database. This observation, which has not been reported previously, could reflect the importance of the physical proximity of related genes, which facilitates their co-regulation, the generation of functionally related genes through tandem duplications or a combination of both phenomena.


Orientation, distance, regulation and function of neighbouring genes.

Gherman A, Wang R, Avramopoulos D - Hum. Genomics (2009)

Gene Ontology clusters. The fraction of gene pairs with membership in common in biological proces clusters for the three types of gene pairs and according to distance. The sliding average approach used in Figure 3 is also applied here. The random expectation is shown with a dashed red line. Abbreviation: GO, gene ontology.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2665707&req=5

Figure 5: Gene Ontology clusters. The fraction of gene pairs with membership in common in biological proces clusters for the three types of gene pairs and according to distance. The sliding average approach used in Figure 3 is also applied here. The random expectation is shown with a dashed red line. Abbreviation: GO, gene ontology.
Mentions: Joint membership of neighbouring genes in functional clusters based on biological processes in the GO database was observed more frequently than expected by chance for all three categories of neighbours and for all distances between adjacent genes (Figure 5). TT and HH genes showed the same increased functional relatedness with each other across all interval sizes. TH genes showed the same increase at distances > 100 kb but significantly greater relatedness at smaller distances. Very similar results were obtained using clusters based on the KEGG pathways database. This observation, which has not been reported previously, could reflect the importance of the physical proximity of related genes, which facilitates their co-regulation, the generation of functionally related genes through tandem duplications or a combination of both phenomena.

Bottom Line: The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes.We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome.We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution.

View Article: PubMed Central - HTML - PubMed

Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.

ABSTRACT
The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes. There are multiple lines of evidence that this arrangement is not random, both in terms of intergenic distances and orientation of neighbouring genes. We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome. We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution. In addition to confirming and extending known properties of the genome, such as the significance of gene deserts and the importance of 'head to head' orientation of gene pairs in proximity, we provide significant new observations that include a smaller average size for intervals separating the 3' ends of neighbouring genes, a correlation of gene expression across tissues for genes as far as 100 kilobases apart and signatures of increasing positive selection with decreasing interval size surprisingly relaxing for intervals smaller than approximately 500 base pairs. Further, we provide extensive graphical representations of the genome-wide data to allow for observations and comparisons beyond what we address.

Show MeSH