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Gene Length & Proximity to Neighbours affect Genome Wide Expression Levels

Gene Length & Proximity to Neighbours affect Genome Wide Expression Levels. Authors: Chiaromonte, Miller and Bouhassira. Content. Introduction Aims of the paper Methods Data Preparation and Processing Statistical Analysis Methods Results Points of Interest Topics for Discussion.

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Gene Length & Proximity to Neighbours affect Genome Wide Expression Levels

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  1. Gene Length & Proximity to Neighbours affect Genome Wide Expression Levels Authors: Chiaromonte, Miller and Bouhassira.

  2. Content • Introduction • Aims of the paper • Methods • Data Preparation and Processing • Statistical Analysis Methods • Results • Points of Interest • Topics for Discussion

  3. Introduction • Steady state levels of mRNA depend on • rate of transcriptional initiation, elongation and termination • efficiency of splicing • rate of export to cytoplasm • stability of mRNA • level of transcription interference (TI)

  4. Aims of the Paper • Identify critical factors that influence gene expression levels • Genome-wide analysis

  5. Achieving the Aims of the Paper • Used both sequence and expression data available from other sources • Used minimal human housekeeping transcriptome (MHKT) to avoid tissue specific expression • Compared expression to various morphological parameters • distance to closest neighbouring gene • gene length • mRNA length • 3’-UTR length • number of exons

  6. Methods 1 • Data Collection and Processing • SAGE tags and tag mapping information • Collation or calculation of values for parameters used

  7. Methods 2 • Statistical Analysis Methods • Natural logarithms • Pearson correlation • Lowess smooths • Added variable plots (AVP) • Significance

  8. Methods Examples Scatter Plot - including lowess smooth and significance calculation Added Variable Plot (AVP)

  9. Results 1 • Highly expressed genes, when compared to gene with lower expression levels, are: • smaller • produce shorter mRNAs with shorter 3’-UTRs • are significantly further from their closest neighbours

  10. Dependence of Expression on Gene Length

  11. Results 2 • Negative association of gene length and expression level • Possible limiting steps: • RNA splicing – no. of exons • mRNA stability – 3’-UTR length and mRNA length • transcriptional elongation – TI

  12. Results 3 • RNA Splicing • slightly positive correlation for genes with < 4 exons • negative correlation for genes with > 4 exons • mRNA Stability • strong negative correlation for both mRNA length and 3’-UTR length

  13. Results 4 • Transcriptional Elongation/Interference • significant positive association between distance between genes and expression • genes with < 100 mRNAs per cell are closer than 100bp to their nearest neighbour • genes with > 500 mRNAs per cell are further from their nearest neighbour • ‘rural’ compared to ‘urban’ genes • ‘rural’ genes have twice the expression levels of ‘urban’ genes • ‘rural’ genes have higher levels of highly expressed genes • morphological parameter effects weakened in ‘urban’ genes

  14. Points of Interest • The cellular and evolutionary implications of gene proximity and TI • The implied primordial genomic organisation

  15. Topics for Discussion • Problems getting onto the websites quoted • Was the number of genes analysed (approx. 1%) sufficient to exclude bias ? • “Substantial remainder effect” allocated to effects of transcriptional elongation and TI, but there may be other factors involved • Statistical confounded of data limits conclusions that can be drawn • Effects of expression levels of neighbouring genes • Gene interactions and is ‘junk’ DNA really junk ?

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