Unlocking the Human Genome: A Comprehensive Guide for Biology Students, Study Guides, Projects, Research of Biology

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The Human Genome Project –

Its History and Advancements into New Research

and Technology

Jutta Marzillier, Ph.D

Lehigh University Biological Sciences September 5th, 2014

Objectives

Techniques that enabled genome sequencing

Process of Human Genome Sequencing

New DNA sequencing Technologies

Some research spinoffs

Guess, who turned

60 last year !!!

The structure of the DNA

double helix:

published in 1953 by Watson

and Crick in the journal of

‘nature’ thereby launching

the ‘Genomic Age’

Guess, who turned

10 last year !!!

Development Sequencing Time Line

2005 1953: Discovery of the DNA double helix by Watson & Crick 2006

How many base pairs (bp) are there in a human genome? How much did it cost to sequence the first human genome? How long did it take to sequence the first human genome? When was the first human genome sequence complete? Why is the Human Genome information important? to serve as a reference for human disease

Genome

Trivia

How many base pairs (bp) are there in a human genome? ~ 3 billion bp (haploid) How much did it cost to sequence the first human genome? ~ $ 3 billion How long did it take to sequence the first human genome? When was the first human genome sequence complete? Why is the Human Genome information important?

Genome

Trivia

How many base pairs (bp) are there in a human genome? ~ 3 billion bp (haploid) How much did it cost to sequence the first human genome? ~ $ 3 billion How long did it take to sequence the first human genome? ~ 13 years When was the first human genome sequence complete? Why is the Human Genome information important?

Genome

Trivia

How many base pairs (bp) are there in a human genome? ~ 3 billion bp (haploid) How much did it cost to sequence the first human genome? ~ $ 3 billion How long did it take to sequence the first human genome? ~ 13 years When was the first human genome sequence complete? ~ 2000- 2003 Why is the Human Genome information important? to serve as a reference for human disease

Genome

Trivia

Why is Genome Sequencing Important?

To obtain a ‘blueprint’ – DNA directs all the instructions needed for

cell development and function

DNA underlies almost every aspect of human health, both, in

function and dis-function

To study gene expression in a specific tissue, organ or tumor

To study human variation

To study how humans relate to other organisms

To find correlations how genome information relates to development

of cancer, susceptibility to certain diseases and drug metabolism

(pharmacogenomics)

Outlook: Personalized Genomics (David Church, Harvard)

DNA Sequencing Biological Dogma and Principle of DNA synthesis Sanger sequencing and its improvements Next-Generation-Sequencing (NGS) Technologies 3 rd Generation Technologies

Projects and ‘Spinoffs’

Outline

‘Dogma of Biology’

The human body has about 100 trillion cells with more than 200 different

cell types.

Each cell harbors the same genetic information in its nucleus in form of

DNA containing chromosomes.

Depending on cellular, developmental, and functional stage of a cell only

a subset of genes is expressed.

Why is the Knowledge about the Human

Genome interesting?

http://www.genomenewsnetwork.org/articles/06_00/sequence_primer.shtml http://www.pharmainfo.net/files/images/stories/article_images/

Principle of DNA Synthesis

Arthur Kornberg demonstrated DNA replication in a cell-free ( in vitro ) bacterial extract (Nobel prize, 1959)

• Discovered DNA polymerase (Pol1) to facilitate DNA synthesis
• Unraveled the mechanism of DNA synthesis
  • nucleotide building blocks
  • a single DNA strand serves as a template
  • can only extend a pre-existing chain (primer)
  • a free 3’ Hydroxyl end is required Watson et al., MGB, 2008

Reaction Mechanism for DNA synthesis

The 3’ hydroxyl group of the primer attacks the -phosphoryl group of the incoming nucleotide thereby forming a phosphodiester bond (SN2 reaction). Watson et al., MBG, 2008 +H+