2. Human Genome Project 1990 Hundreds of Disease Genes Identified High-Resolution Physical and Genetic Maps Completed DNA Sequence of Model Organisms Completed Private Private Sector Sector Participation Participation Framework DNA Sequence Completed DNA Sequence Completed Completed Complex Genetic Genetic Disease Disease Functional Genomics Genomics Biotechnology 1995 2000 2003

5. Macro Quality Control Micro Short (40 Nucleotide) Oligomer Synthesized from Sequence Primer Sets for PCR / Sequencing of Genomic DNA RARE Cleavage of Genomic DNA (RecA-Assisted Restriction Endonuclease) CH 3 RecA Protein Triple Helix Protected from Methylation Endonuclease Digestion and Pulsed-Field Gel Analysis Confirmation of Assembly / Sequence Identification of SNPs

7. ECRs Comparative Analysis Human Populations Primates

8. ECRs Estimate Gap Length RARE cleavage Can also be used to confirm current assemblies and uncover large-scale polymorphisms Clone Gaps TAR cloning

9. A lovely Bai little girl

10. DRD4 5’ 3’ Exon1Exon2Exon3Exon4 120 bp Duplication (L/S) 12 bp Duplication (L/S) 48 bp VNTR 2R 3R 4R 5R 6R 7R 8R 9R 10R 48 bp VNTR (Numerous SNPs) 8.8% 65.1% 19.2% 11R G/AG/C 2.4% 1.6% 2.2% 0.6% <0.1% SNPs

12. 3R-ALLELE 2R-ALLELE 4R-ALLELE 6R-ALLELE 5R-ALLELE 7R-ALLELE 1-2-3-4 1-4 1-2-3-4 1-7-4 1-2-3-4 1-2-3-2-3-4 1-2-2-3-4 1-2-3-4 1-2-6-5-2-5-4 (1-2-6-5-2-5-4) Multiple Mutations/ Gene Conversions L L S S A - C L L A-C S S G - G 8R-ALLELE 6R-ALLELE 5R-ALLELE G - G A - C