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

2 Outline Background Methods Results Conclusion

3 Background DNA  RNA  PROTEIN

4 Background  PROTEIN Splicing( 剪接 ) DNA 

5 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。

6 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

7 Methods Construction of the splicing graph and systematic splicing pattern detection

8 Methods Classification of alternative splicing events

9 Methods

10 Methods Decomposition of splicing graphs into splicing patterns

11 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.

12 Results

13 Results

14 Results

15 Results

16 Results

17 Results

18 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.

19 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 eventleast common events

20 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.