1. Genome Annotation and the landscape of the Human Genome Gabor T. Marth Department of Biology, Boston College marth@bc.edu BI420 – Introduction to Bioinformatics

2. Genome annotation – Goals protein coding genesRNA genes repetitive elements GC content

3. The starting material AGCGTGGTAGCGCGAGTTTGCGAGCTAGCTAGGCTCCGGATGCGA CCAGCTTTGATAGATGAATATAGTGTGCGCGACTAGCTGTGTGTT GAATATATAGTGTGTCTCTCGATATGTAGTCTGGATCTAGTGTTG GTGTAGATGGAGATCGCGTAGCGTGGTAGCGCGAGTTTGCGAGCT AGCTAGGCTCCGGATGCGACCAGCTTTGATAGATGAATATAGTGT GCGCGACTAGCTGTGTGTTGAATATATAGTGTGTCTCTCGATATGT AGTCTGGATCTAGTGTTGGTGTAGATGGAGATCGCGTGCTTGAG TCGTTCGTTTTTTTATGCTGATGATATAAATATATAGTGTTGGTG GGGGGTACTCTACTCTCTCTAGAGAGAGCCTCTCAAAAAAAAAGCT CGGGGATCGGGTTCGAAGAAGTGAGATGTACGCGCTAGXTAGTAT ATCTCTTTCTCTGTCGTGCTGCTTGAGATCGTTCGTTTTTTTATGCT GATGATATAAATATATAGTGTTGGTGGGGGGTACTCTACTCTCTCT AGAGAGAGCCTCTCAAAAAAAAAGCTCGGGGATCGGGTTCGAAGA AGTGAGATGTACGCGCTAGXTAGTATATCTCTTTCTCTGTCGTGCT

4. Coding genes – ab initio predictions ATGGCACCACCGATGTCTACGTGGTAGGGGACTATAAAAAAAAAAA Open Reading Frame = ORF Stop codon Start codon PolyA signal

5. Ab initio predictions Gene structure

6. Ab initio predictions …AGAATAGGGCGCGTACCTTCCAACGAAGACTGGG… splice donor site splice acceptor site

7. Ab initio predictions Genscan Grail Genie GeneFinder Glimmer etc… EST_genome Sim4 Spidey

8. Homology based predictions ATGGCACCACCGATGTCTACGTGGTAGGGGACTATAAAAAAAAAAA ACGGAAGTCT known coding sequence from another organism GGACTATAAA expressed sequence genes predicted by homology Genomescan Twinscan etc…

9. Consolidation – gene prediction systems Otto Ensembl FgenesH Genscan Grail Genewise Sim4 dbEst

10. ncRNA genes prediction based on structure (e.g. tRNAs) for other novel ncRNAs, only homology-based predictions have been successful

11. Repeat annotations Repeat annotation are based on sequence similarity to known repetitive elements in a repeat sequence library

12. The landscape of the human genome

13. Gene annotations – # of coding genes

14. Gene annotations – gene length

15. Gene annotations – gene function

16. GC content and coding potential

17. ncRNAs

18. Segmental duplication

19. Repeat elements

20. Genes and repeats

21. Physical vs. genetic map (MB/cM)

22. Synteny (human-mouse)

23. Gene duplication – paralogs

24. Gene classes across organisms

25. Gene conservation across organisms

26. Human SNPs – polymorphism rate in different regions of given lengths at the scale of the chromosomes

27. Human SNPs – polymorphism rate G+C nucleotide content CpG di-nucleotide content recombination rate functional constraints 3’ UTR5.00 x 10 -4 5’ UTR4.95 x 10 -4 Exon, overall4.20 x 10 -4 Exon, coding3.77 x 10 -4 synonymous 366 / 653 non-synonymous287 / 653

28. Human SNPs – polymorphism rate