1 genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human...

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1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC Genomics 2009 Speaker:JIA-CHI LEE Date:2011/05/27

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Page 1: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases

Author: Elsa Chacko and Shoba Ranganathan

Source:BMC Genomics 2009

Speaker:JIA-CHI LEE

Date:2011/05/27

Page 2: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Outline

Background Methods Results Conclusion

Page 3: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Background

DNA

RNA

PROTEIN

Page 4: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Background

PROTEIN

Splicing( 剪接 )

DNA

Page 5: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Background Alternative splicing ( 選擇性剪接 ) :利用這樣的特性,將同一基因中的 exon 以不同的組合方式來表現,使一個基因在不同時間、不同環境中能夠製造出不同的蛋白質,可增加生理狀況下系統的複雜性 / 適應性。

Page 6: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Background It is critical to conduct an in-depth study on AS

because it has been observed that the disruption of AS is associated with many diseases such as cardiovascular, cancer and neurodegenerative disorders.

we have developed component sub-graphs, called "splicing patterns" which provide a rapid and automatic analytical system for complete dissection of transcript diversity.

心血管 癌症神經退化 / 失調

Page 7: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Methods Construction of the splicing graph and

systematic splicing pattern detection

Page 8: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Methods Classification of alternative splicing

events

Page 9: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Methods

Page 10: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Methods Decomposition of splicing graphs into

splicing patterns

Page 11: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Methods Exon and intron size analyses We have analysed the exon and intron size conservation

across the three genomes for the alternatively spliced genes and orthologous AS genes.

Exon number analysis The number of exons per transcript was analysed for the

three genomes.

Splicing motif analysis The frequencies were calculated for GT-AG, GC-AG and AT-AC

type splice motifs.

Page 12: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 13: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 14: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 15: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 16: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 17: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Results

Page 18: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Conclusion We have developed a novel subgraph-based

analytical scheme for comparative transcriptome analysis, using a set of four discrete splicing patterns.

This is the first comprehensive study of the bovine transcriptome, with 21% of bovine genes exhibiting alternative splicing, compared to 68% and 57% in human and mouse, respectively.

Page 19: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Conclusion The most common AS event was found to be exon

skipping and the least common events were intron retention and mutually exclusive exons.

With predominantly introns linking two variable exons, as opposed to human and mouse genes fewer AS bovine genes show high transcript variability.

most common event least common events

Page 20: 1 Genome-wide analysis of alternative splicing in cow: implications in bovine as a model for human diseases Author: Elsa Chacko and Shoba Ranganathan Source:BMC

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Conclusion Our analysis it is evident that AS plays a major

role in disease implications in both human and cow, and is suitable as a model for investigating human diseases.