National Dong Hwa University Genome Biology David Shiuan Department of Life Science, Institute of Biotechnology and Interdisciplinary Program of Bioinformatics National Dong Hwa University

Genome Sizes Pine: 68 billion bp Corn: 5.0 billion bp Soybean: 1.1 billion bp Human: 3.4 billion bp Housefly: 900 million bp Rice: 400 million bp E. coli: 4.6 million bp HIV: 9.7 thousand bp http://www.cbs.dtu.dk/databases/DOGS/abbr_table.txt

How Big Is 3.4 Billion? Human genome is 3.4 B bp If the bases were written in standard 10-point type, on a tape measure......The tape would stretch for 5,366 MILES! Identifying a 500 bp sequence in a genome would be like finding a section of this tape measure only 4 feet long...

Greatest Breakthroughs in Human History Manhattan Project ~1940/1944 (Nuclear Energy) Apollo Project ~1960/1972 (Moon Landing) Human Genome Project ~1990/2003 (Decoding the Book of Life)

The Human Genome Project A publicly financed international research effort. Goal : to decipher the human genetic code and to provide these data freely and rapidly to the public. Draft announced Jun 2000 Project completed Apr 2003

Director of the Human Genome Project and the National Human Genome Research Institute (NHGRI). He found the gene responsible for cystic fibrosis, Huntington's disease, neurofibromatosis, multiple endocrine neoplasia type 1, and the M4 type of adult acute leukemia. Venter founded The Institute for Genomic Research mapping the human genome. At NIH, Venter learned of a technique for rapidly identifying all of the mRNAs present in a cell, and began to use it to identify human brain genes.

in 2000 President Clinton's remarks announcing completion of the first phase of the project : "Today we are learning the language in which God created life.“ Collins insists that "science is not threatened by God; it is enhanced" and "God is not threatened by science; He made it all possible."

How the genome sequences were determined ?

A even bigger improvement! Yeast artificial chromsomes (YACs) and bacterial artificial chromsomes (BACs) Can accomodate from 300 – 500 kb of DNA – great for large genomes For the human genome and a standard plasmid P – 99% or 0.99 confidence f – 500 kb/4,400,000 kb = 1.14 x 10-4 N = [ln .01]/[ln 0.999886] = -4.6/-1.14 x 10-4 = 40,350 individuals A even bigger improvement!

YAC(Yeast artificial chromsome) Reeves et al., 1992, Methods Enzymol. 216:584-603 YAC(Yeast artificial chromsome) self-replicating vector that can be maintained in yeast Can accommodate large insert

DNA Auto-Sequencers

MUMmer: fast alignment of large-scale DNA and protein sequences

Annotating the Human Genome Two Tasks: correct placement of known genes into the proper genomic context prediction of previously unknown genes based on the assembled genomic sequence. 

What are the bacterial-unique genes/proteins?

Vaccine Design ? Antibiotics Discoveries ?

Human Proteome Initiative Sep 2007

Post Genomic Era From one gene, one protein  genome and proteome From one to one interaction  cluster of interactions, pathways and systems (biology)