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

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.

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.

in 2000President 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 ?

Can accomodate from 300 – 500 kb of DNA – great for large genomes

Yeast artificial chromsomes (YACs) and bacterial artificial chromsomes (BACs)

N = [ln .01]/[ln 0.999886] = -4.6/-1.14 x 10-4

= 40,350 individuals

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

A even bigger improvement!

YAC(Yeast artificial chromsome)

self-replicating vector that can be maintained in yeast

Can accommodate large insert

Reeves et al., 1992, Methods Enzymol. 216:584-603

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)