HUMAN

GENOME
PROJECT

Carol Zubiría for SCW 2012-13

 Introduction

Human genome: more than 3M "letters" A,C, T & G

First mapped and sequenced: from 1990 to 2003.

The Human Genome Project (HGP) international initiative

Sequencing the human genome:

●identify important genes and regulatory regions.
●better understand their role in disease.
●investigate our origins using variations in the DNA
sequence.
Introduction

Like 200 yellow pages books.

 What was the Human Genome Project?

●HGP aim: sequence the entire human genome

and provide the data free to the world.

●First major global collaboration of its kind and the

largest biological research project ever
undertaken, involving thousands of staff in
institutes across the globe.

●By assigning different portions of the genome to

different research groups in a coordinated and
efficient way, the HGP researchers were able to
What was the Human Genome Project?
 Who took part in the project?

Twenty institutes from six different countries

(China, France, Germany, Japan, UK and USA)

●Wellcome Trust Sanger Institute

●Washington University School of Medicine
●Whitehead Institute/MIT centre for Genome
research
●The DOE’s Joint Genome Institute
●Baylor College of Medicine
How was the human genome sequenced?

●Sequencing technology: only a few hundred

base pairs of DNA at a time.
●It had to be broken up into small pieces for
sequencing → giant jigsaw puzzle.
●First 200,000 base pair sections (clones)
●Inserted into bacterial DNA, living libraries of
the DNA clones.
●Shipped between collaborating institutes.
●Clones then broken into smaller pieces
(4000-6000 base pairs).
How was the human genome sequenced?

●Clones then broken into smaller pieces

(4000-6000 base pairs)
●Re-inserted into bacteria
●Cultured to make enough DNA for
sequencing.
●Bacterial colonies transferred to tubes →
lysed → DNA extracted.
●Sanger sequencing method.
●Resulting data pieced together to form the
whole genome sequence.
How was the human genome sequenced?
 How long did the HGP take?

●HGP took 13 years.

●Expected more than 15 years.

●Started: October 1990

●First “draft”: June 2000

●Finished sequence: April 2003

●Published: 2004.

●Work continues to refine the “reference”

human genome sequence.

Who has access to the human genome data?

●Put simply, everyone.

●Provide free and open access to the data
for everyone in the scientific community and
the public domain.
●Deposited in freely available, online public
databases.
●Genome browsers: www.ensembl.org
●Access to more than 50 species’ genomes.
What happened after the HGP was finished?

Officially finished.
●

●Research continues on the human reference

sequence.

Filling in the “gaps” in the sequence.

●

SNPs (single nucleotide polymorphisms):

●

Genetic variation differences in single bases.

What happened after the HGP was finished?

HapMap project: 3 year → chart the patterns of

●
genetic variation common in the world’s population.

Results 2005 simplify studies to understand how

●
genetic variation contributes to health and disease.
 1000 Genomes Project

●International research consortium.

●Launched in January 2008.

●Aim: to sequence the genomes of at least a

thousand people from around the world, to
identify very clearly those variations
between individuals that are medically
important and map these on the genome.
 Genome sequencing Evolution

HGP
● 13 years Billions $

Watson 2007
● 4 months $1M

Helicos 2009
● 1 month $ 48.000

Now
● 1 or 2 weeks 6.000 €
 Genome sequencing NOW

How are genes activated?

Genes regulation by regulatory regions.

8.4 M (10 to 20 letters) identified.

Variations in regulatory regions: high risk

diseases.
Gene therapy