1. http://cs273a.stanford.edu [Bejerano Aut07/08] 1 MW 11:00-12:15 in Redwood G19 Profs: Serafim Batzoglou, Gill Bejerano TA: Cory McLean

2. http://cs273a.stanford.edu [Bejerano Aut07/08] 2 Lecture 11 Human Genes Vertebrate Gene Cis-Regulation

3. http://cs273a.stanford.edu [Bejerano Aut07/08] 3 What People Largely Expected to Find gene (how to) control region (when & where) DNA proximal: in 10 3 letters genome.ucsc.edu 3kb

4. http://cs273a.stanford.edu [Bejerano Aut07/08] 4 How They Measured all human-mouse alignments human-mouse ancestral repeats alignment Difference: 5% of Human Genome [Mouse consortium, Nature 2002]

5. http://cs273a.stanford.edu [Bejerano Aut07/08] 5 Other Ways to Measure [Lunter et al, 2006] [Cooper et al., 2005]

6. http://cs273a.stanford.edu [Bejerano Aut07/08] 6 Human Genome: 3*10 9 letters What They Found [Science 2004 Breakthrough of the Year, 5 th runner up] 1.5% known function >50% junk 3x more functional DNA than known! compare to other species >5% human genome functional ~10 6 substrings do not code for protein What do they do then?

7. http://cs273a.stanford.edu [Bejerano Aut07/08] 7 The Gene-ome makes < 2% of the H.G. [Human Molecular Genetics, 3rd Edition]

8. http://cs273a.stanford.edu [Bejerano Aut07/08] 8 Gene Finding – The Practice Challenge: “The genes, the whole genes, and nothing but the genes” Problems: spliced ESTs  legitimate gene isoform? predicting gene isoforms tissue/condition specific genes / gene isoforms single exon genes pseudogenes Practice:

9. http://cs273a.stanford.edu [Bejerano Aut07/08] 9 Evolution of Gene Finding Tools etc

10. http://cs273a.stanford.edu [Bejerano Aut07/08] 10 The Human Gene Set [HGC, 2001]

11. http://cs273a.stanford.edu [Bejerano Aut07/08] 11 [Celera, 2001]

12. http://cs273a.stanford.edu [Bejerano Aut07/08] 12 wrong!

13. http://cs273a.stanford.edu [Bejerano Aut07/08] 13 Horizontal Gene Transfer

14. http://cs273a.stanford.edu [Bejerano Aut07/08] 14 Horizontal Gene Transfer in the H.G. [HGC, 2001] …

15. http://cs273a.stanford.edu [Bejerano Aut07/08] 15 Or is it? [Kurland et al., 2003]

16. http://cs273a.stanford.edu [Bejerano Aut07/08] 16 HGT between fish & their parasites

17. http://cs273a.stanford.edu [Bejerano Aut07/08] 17 Gene regulation = when/where to make protein gene (how to) control region (when & where) DNA ~10 3 letters

18. http://cs273a.stanford.edu [Bejerano Aut07/08] 18 Vertebrate Transcription Regulation

19. http://cs273a.stanford.edu [Bejerano Aut07/08] 19 unicellular multicellular Unicellular vs. Multicellular

20. http://cs273a.stanford.edu [Bejerano Aut07/08] 20 Vertebrate Gene Regulation gene (how to) control region (when & where) DNA proximal: in 10 3 letters distal: in 10 6 letters DNA binding proteins

21. http://cs273a.stanford.edu [Bejerano Aut07/08] 21 Pol II Transcription Key components: Proteins DNA sequence DNA epigenetics Protein components: General Transcription factors Activators Co-activators

22. http://cs273a.stanford.edu [Bejerano Aut07/08] 22 Activators & Co-Activators Protein - DNA Protein - Protein