1. 1 Genomics The field of biology based on studying the entire DNA sequence of an organism - its “genome”. Genomics tools don’t replace classical genetics tools, they are complementary.

2. 2 1. Mutant studies A. Find mutants and reproduce them Natural mutations Create mutations by using mutagens (selective pressure for mutants to survive) example: antibiotic resistant bacteria B. Study genes one at a time Classical Genetics (forward genetics) :

3. 3 What makes Genomics a new way to study biology? Genomics: Using tools to study all the genes in an organism (the entire genome) simultaneously once its sequence is known. (~ 190 organisms as of March 2007) How do we do this?

4. 4 1. Work with Model Organisms - Share resources and information Be Efficient: Genomics methods E. coli (Bacterium) Drosophila (Fruit Fly) Arabidopsis (Plant) Mouse ZebraFishS. cerevisiae (Yeast) Dictyostelium (Slime mold) C.elegans (Worm) Xenopus (African clawed frog)

5. 5 2. Use Reverse Genetics: A. Insert tagged DNA sequences (T-DNA) at random sites throughout the genome. If the insertion disrupts a gene, then it might cause an observable phenotype. B. Grow the organism. C. Look for mutant phenotypes. Genomics methods cont’d.…Since the insertion has a specific sequence (a tag), you can figure out where the insertion went in the genome =>then you figure that gene is related to that phenotype. Voilà!

6. 6 Genomics Methods, Cont’d ==> One method is a Microarray 3. Use High through-put methods that produce huge datasets

7. 7 Microarrays (slang: DNA chips) Ordered array of different known sequences of DNA (~20-70 bp) on a solid surface (glass) Gene 1 Gene 2 Gene 18 Can have thousands of “spots”. This slide has 18

8. 8 “DNA Chip” Slang for DNA Microarray =>Technology using a biological molecule: DNA many different DNA sequences stuck to a flat surface tens of thousands of spots can probe tens of thousands of DNA sequences all at once A T G C

9. 9 How do Microarrays work? 1. Cells express certain genes under certain conditions and make RNA 2. RNA is isolated and tagged with a dye 3. Tagged RNA is placed on a microarray containing representative sequences of thousands of genes at known addresses on the chip 4. Microarray is scanned to locate where dye is => this is where RNA has attached => voila! these genes were expressed In general:

10. 10 Labeled Target DNA made from RNA present in cells (a “snapshot” of gene expression) Temple Smith, Boston U Probe DNA stuck to glass Hybridized target to Probe DNA