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MW 11:00-12:15 in Redwood G19 Profs: Serafim Batzoglou, Gill Bejerano TA: Cory McLean http://cs273a.stanford.edu [Bejerano Aut07/08] 1 Lecture 11 Human Genes Vertebrate Gene Cis-Regulation http://cs273a.stanford.edu [Bejerano Aut07/08] 2 What People Largely Expected to Find DNA proximal: in 103 letters 3kb http://cs273a.stanford.edu [Bejerano Aut07/08] gene (how to) control region (when & where) genome.ucsc.edu 3 How They Measured all human-mouse alignments human-mouse ancestral repeats alignment Difference: 5% of Human Genome [Mouse consortium, Nature 2002] http://cs273a.stanford.edu [Bejerano Aut07/08] 4 Other Ways to Measure [Lunter et al, 2006] [Cooper et al., 2005] http://cs273a.stanford.edu [Bejerano Aut07/08] 5 What They Found Human Genome: 3*109 letters 1.5% known function compare to other species >50% junk >5% human genome functional 3x more functional DNA than known! ~106 substrings do not code for protein What do they do then? [Science 2004 Breakthrough of the Year, 5th runner up] http://cs273a.stanford.edu [Bejerano Aut07/08] 6 The Gene-ome makes < 2% of the H.G. [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Aut07/08] 7 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: http://cs273a.stanford.edu [Bejerano Aut07/08] 8 Evolution of Gene Finding Tools etc http://cs273a.stanford.edu [Bejerano Aut07/08] 9 The Human Gene Set [HGC, 2001] http://cs273a.stanford.edu [Bejerano Aut07/08] 10 [Celera, 2001] http://cs273a.stanford.edu [Bejerano Aut07/08] 11 wrong! http://cs273a.stanford.edu [Bejerano Aut07/08] 12 Horizontal Gene Transfer http://cs273a.stanford.edu [Bejerano Aut07/08] 13 Horizontal Gene Transfer in the H.G. … [HGC, 2001] http://cs273a.stanford.edu [Bejerano Aut07/08] 14 Or is it? [Kurland et al., 2003] http://cs273a.stanford.edu [Bejerano Aut07/08] 15 HGT between fish & their parasites http://cs273a.stanford.edu [Bejerano Aut07/08] 16 Gene regulation = when/where to make protein gene (how to) control region (when & where) DNA ~103 letters http://cs273a.stanford.edu [Bejerano Aut07/08] 17 Vertebrate Transcription Regulation http://cs273a.stanford.edu [Bejerano Aut07/08] 18 Unicellular vs. Multicellular unicellular multicellular http://cs273a.stanford.edu [Bejerano Aut07/08] 19 Vertebrate Gene Regulation distal: in 106 letters gene (how to) control region (when & where) DNA proximal: in 103 letters http://cs273a.stanford.edu [Bejerano Aut07/08] DNA binding proteins 20 Pol II Transcription Key components: • Proteins • DNA sequence • DNA epigenetics Protein components: • General Transcription factors • Activators • Co-activators http://cs273a.stanford.edu [Bejerano Aut07/08] 21 Activators & Co-Activators Protein - Protein Protein - DNA http://cs273a.stanford.edu [Bejerano Aut07/08] 22