1. BI820: Seminar in Quantitative and Computational Problems in Genomics
The Sequence of the Human Genome J Craig Venter, et al. Science (2001)
Dean Wagner
BI820: Seminar in Quantitative and Computational Problems in Genomics
1/27/04

2. Why sequence the human genome?
To Understand:
human evolution
disease
environment/ heredity

3. History ? Venter, et al. Science 291, 1304 (2001) 1998 PE Biosystems
Mya
Homo habilis
1987
Applied Biosystems
13.7Bya
Universe
Formed
1977
Sanger
1985
Sinsheimer
1995
H. influenzae
6/17/00
1865/1900
Mendel
9/8/99 ?
Seeburg, et al.
Celera
10/1/00
4-5Mya
Ardipithecus
ramidus
1986
Hood, et al.
1997
Weber and Myers
1953 Watson
and Crick
1982
Bacteriophage 
5/99 Dm
120,000ya
Homo sapiens
(modern)
2000
Drosophila
1990
HGP
ISGSC
Nature 409, 860 (2001)

4. Sanger Inst.

5. Sanger Inst.

6. Why WGS Can’t Be Done
Against a Whole Genome Shotgun Phillip Green Genome Research 7, 410
unable to finish
error prone
unable to distinguish pseudogenes
Repeats
SNPs or errors
logistics
high cost

7. How WGS Can Be Done
Genomic Mapping by Fingerprinting Random Clones: A Mathematical Analysis
Eric S. Lander and Michael S. Waterman
Genomics 2, 231
{e-cf()d }-1[ -1-  L e -c/(1- e -c)f(L, )dLd ]+  L(1- )f(L, )dLd 
Proof:
4(1/22)k+ 4(1/22)k+1+ 4(1/22)k (1/22)k(1+ 4(1/22)

8. Results >26,000 protein-encoding transcripts ~12,000 more?
2.1M SNPs
<1% SNPs variation in proteins
1/1,250nt difference be individuals

9. Compare WGS Clone by Clone speed accuracy cost modularity
early broad samplings
Clone by Clone
accuracy
modularity
target regions