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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
Brain expression across individuals. Correlation of neighbouring gene expression in the temporal lobe of the brain across multiple individuals and according to gene pair type and distance. The sliding average approach used in Figure 3 is also applied here.
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Figure 7: Brain expression across individuals. Correlation of neighbouring gene expression in the temporal lobe of the brain across multiple individuals and according to gene pair type and distance. The sliding average approach used in Figure 3 is also applied here.

Mentions: Correlation of expression across individuals within the same tissue type (Figure 7) examines a different aspect of co-regulation, suggesting polymorphic sequence variants acting on both genes and/or common regulation in response to exposures or sample properties (age, sex, cause of death etc). We examined 13 males and ten females with an average age of 76 years (range 35-95). Both genes were expressed in the brain and had available data for 4,837 pairs (2,372 TH, 1,267 HH and 1,198 TT). For all pairs, we observed higher interindividual expression correlation (average r = 0.086) than for 20,000 random gene pairs (r = 0.004; p < 10-22). This remained constant up to interval sizes of about 100 kb, at which size it was no longer increased for TT or TH intervals. The examination of interindividual correlation of expression for neighbouring genes is novel and it is interesting that the results are different from analyses across tissues, with increased correlation but a lack of change with distance. This suggests that gene distance between co-regulated genes is only important for factors determining tissue specificity, and not so important for variation of expression within a tissue.


Orientation, distance, regulation and function of neighbouring genes.

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

Brain expression across individuals. Correlation of neighbouring gene expression in the temporal lobe of the brain across multiple individuals and according to gene pair type and distance. The sliding average approach used in Figure 3 is also applied here.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Brain expression across individuals. Correlation of neighbouring gene expression in the temporal lobe of the brain across multiple individuals and according to gene pair type and distance. The sliding average approach used in Figure 3 is also applied here.
Mentions: Correlation of expression across individuals within the same tissue type (Figure 7) examines a different aspect of co-regulation, suggesting polymorphic sequence variants acting on both genes and/or common regulation in response to exposures or sample properties (age, sex, cause of death etc). We examined 13 males and ten females with an average age of 76 years (range 35-95). Both genes were expressed in the brain and had available data for 4,837 pairs (2,372 TH, 1,267 HH and 1,198 TT). For all pairs, we observed higher interindividual expression correlation (average r = 0.086) than for 20,000 random gene pairs (r = 0.004; p < 10-22). This remained constant up to interval sizes of about 100 kb, at which size it was no longer increased for TT or TH intervals. The examination of interindividual correlation of expression for neighbouring genes is novel and it is interesting that the results are different from analyses across tissues, with increased correlation but a lack of change with distance. This suggests that gene distance between co-regulated genes is only important for factors determining tissue specificity, and not so important for variation of expression within a tissue.

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