1. What is genomics? Genes, promoters, regulatory elements, alignments, trees, …

2. What is the “Genome”? Protein 3 billion units (nucleotides) 10000 6-15 Sizes:

3. GGGCTGGGCGAGTATCTCTTCGAAAGGCTCACTCTCAAGCACGACTAAGAGCCTTCTGAGC...... What is genomics?...

4. GGGCTGGGCGAGTATCTCTTCGAAAGGCTCACTCTCAAGCACGACTAAGAGCCTTCTGAGC...... What is genomics? GLGEYLFERLTLKHD*.....

5. What is genomics? TTCCTTAGACTCTTAGAAAGTACCTCAAAAACGAAATGCG AACAC........

6. What is genomics? TTCCTTAGACTCTTAGAAAGTACCTCAAAAACGAAATGCG AACAC.......

7. What is genomics? TTCCTTAGACTCTTAGAAAGTACCTCAAAAACGAAATGCG AACAC....... ATGGAGT........ microRNA

8. What is comparative genomics? TTCCCTAG--------CAAGTACCTCA------------------ TTCCCTAG--------CAAGTACCTCA------------------ TTCCCTAG--------CAAGTACCTCA------------------ TTCCTTAGACTCTTAGCAAGTACCTCA------------------ TTCCTTAGACTCTTAGAAAGTACCTCAAAAACGAAATGCG AACACGACTCT---- TTTTAGCAAGTACCTCAAAATATTTAATTAAA-AC ACTCTT- ---TTTTAGCAAGTACCTCAAGAATTACAATTAAATAT TTCCTTAGACTCTTAGAAAGTACCTCAAAAACGAAATGCGAACAC Grun et al. microRNA target predictions across seven Drosophila species and comparison to mammalian targets, PloS Computational Biology, June 2005 Lall et al. A genome wide map of conserved microRNA targets in C. Elegans, submitted to Cell, 2005. ATGGAGT........ let-7

9. The Drosophila Genome Project 1911 Genetic Mapping in Drosophila Sturtevant and Morgan 2000 Drosophila melanogaster genome sequenced Celera and LBNL publish Drosophila genome in Science 2003 Proposal for Drosophila as a model system for comparative genomics Clark, Gibson, Kaufman, McAllister, Myers, O’Grady 2005 Twelve Drosophila genomes sequenced Consortium involving Agencourt, Broad Institute, Baylor College Medicine, Washington University St. Louis and the Venter Institute.

10. http://species.flybase.net/ Female Male Karyotype A project to compare and contrast Drosophila

11. http://rana.lbl.gov/drosophila/wiki/

12. BP England, U Heberlein, R Tjian. Purified Drosophila transcription factor, Adh distal factor-1 (Adf-1), binds to sites in several Drosophila promoters and activates transcription, J Biol Chem 1990.

13. S. Chatterji and L. Pachter, GeneMapper: Reference based annotation with GeneMapper,2005.

14. Alignment of an exon DroAna_20041206_ GTCGCTCAACCAGCATTTGCAAAAGTCGCAGAACTTGCGCTCATTGGATTTCCAGTACTC DroEre_20041028_ GTCGCTCAGCCAGCATTTGCAGAAGTCGCAGAACTTCCGCTCGTTTGACTTCCAGTACTC DroMel_4_ GTCGCTCAGCCAGCATTTGCAGAAGTCGCAGAACTTGCGCTCGTTTGATTTCCAGTACTC DroMoj_20041206_ GTCGCTTAACCAGCATTTACAGAAATCGCAATACTTGCGTTCATTGGATTTCCAGTACTC DroPse_1_ GTCGCTCAGCCAGCACTTGCAGAAGTCGCAGTACTTGCGCTCGTTTGATTTCCAGAATTC DroSim_20040829_ GTCGCTCAGCCAGCA-TTGCAGAAGTCGCAGAACTTGCGCTCGTTTGATTTCCAGTACTC DroVir_20041029_ GTCGCTCAACCAGCATTTGCAGAAGTCGCAATACTTGCGTTCATTCGACTTCCAGTACTC DroYak_1_ GTCGCTCAGCCAGCATTTGCAGAAGTCGCAGAACTTCCGCTCGTTTGACTTCCAGTACTC ****** * ****** ** ** ** ***** **** ** ** ** ** ****** * **

16. Is the Adf1 binding site conserved? mel TGTGCGTCAGCGTCGGCCGCAACAGCG pse TGT-----------------GACTGCG *** ** *** mel TGTG----CGTCAGC--G----TCGGCC---GC-AACAG-CG pse TGTGACTGCG-CTGCCTGGTCCTCGGCCACAGCCAAC-GTCG **** ** * ** * ****** ** *** * ** mel TGTGCGTCAGC------GTCGGCCGCAACAGCG pse TGTGACTGCGCTGCCTGGTCCTCGGCCACAGC- **** * ** *** * ** *****

17. Characterizing promoters: The APO(a) gene Plasminogen (PLG) APO(a) (LPA) Part of the apolipoprotein gene family Regulation not well understood High plasma levels of the protein important risk factor for cardiovascular disease

18. Human Baboon Chimp Apo(a) : Limited Distribution Among Mammals Hedgehog Plasminogen (PLG) APO(a) (LPA) Lemur (prosimian) Mouse New-World Monkeys

22. A G G C C A G C T A G G C C A G C A A G A G C A G C A A G A C C A G C A ACGTACGT ACGT A A A A A G G G C G neutral constrained compute two numbers: fast lik & slow lik

23. 250500 750 1000 1250 1500 1750 2000 2250 Phylogenetic shadowing of the apo(a) promoter conserved non-conserved TATA HNF-1  EXON sequence position (bp)

24. Gel-shift assay to assess DNA-protein interactions nuclear extract non-conserved elements conserved elements DNA-protein complex unbound DNA

25. nuclear extract non-conserved elements conserved elements DNA-protein complex unbound DNA Gel-shift assay to assess DNA-protein interactions

26. nuclear extract non-conserved elements conserved elements DNA-protein complex unbound DNA

27. Gel-shift analysis of conserved elements in the apo(a) promoter 1 2 3 4 5 6 7 8 9 10-1 10-2 Non-conserved elements 1 2 3 4 5 6 7 Conserved elements

29. ENCODE pilot phase 1% of the genome. 44 regions target selection. commitee has selected sequence targets –manual targets – a lot of information –radom targets – stratified by non exonic conservation with mouse by gene density