The Human Genome Project

Before HGP
1953 DNA structure determined (Watson and Crick)

HSE ZOOLOGY BLOG

The Human Genome Project

Before HGP
1966 genetic code deciphered

DNA sequence

Protein sequence
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The Human Genome Project

Before HGP
1975 method for DNA sequencing introduced

Frederick Sanger
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The Human Genome Project

Before HGP
1985 DNA amplification by PCR

Kary Mullis

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The Human Genome Project

Before HGP
1986 Plans to start HGP

HGP?
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Human Genome
Begun formally in 1990, the U.S. Human Genome Project was a 13-year effort coordinated by the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH). The project originally was planned to last 15 years, but rapid technological advances accelerated the completion date to 2003.

Human Genome
Estimated that it cost $3 billion over the 15 year project that was funded by the Department of Energy It began in 1988 and the first draft was announced in 2000 with the more complete version released in 2003 (2 years ahead of schedule)

THE HUMAN GENOME PROJECT

Identify 20,000-25,000 genes in human DNA Determine the sequences of the over 3 billion base pairs that make up Human DNA Store this information in databases to be available for public use Improve tools for Data Analysis Transfer related technologies to the private sector Address the ethical, legal, and social issues that may arise from the project

The Human Genome Project

HGP
1999 Chromosome 22 sequenced
2001 Working drafts published: o Public HGP in Nature

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The Human Genome Project

HGP
2003 Completion of HGP

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The Human Genome Project

Sequencing Methods

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The Human Genome Project

DNA Sequencing Methods

Sequence Annotation Expressed Sequence Tags (ESTs)

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GENOME SEQUENCING
Chromosomes must first be broken into shorter pieces. Each piece is used as a template to generate new DNA fragment strands from replication Fragments are placed in a machine called gel electrophoresis which uses a electric charge (because DNA has an overall negative charge) to distribute DNA fragment strands based on density (the heavier the fragment the closer to the bottom of the machine). Fluorescent dyes allow for identification of fragments: For Example: A- Green Dye T-Blue Dye C- Yellow Dye G- Red Dye

The Human Genome Project

Top-down approach
DNA library generation Gene mapping by

genetic markers

Sequencing reaction Electrophoresis Analysis

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The Human Genome Project

Shotgun Sequencing
Generation DNA library
Sequence alignment Multiple sequencing events

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The Human Genome Project

FINDINGS

The human genome contains 3164.7 million chemical nucleotide bases (A, C, T, and G). The average gene consists of 3000 bases,

The largest known human gene is coding for dystrophin.

The total number of genes is estimated at 30,000 Functions are unknown for over 50% of discovered genes.

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FACTS PROVIDED BY THE HGP

The average human gene consists of 3000 bases (subject to variation). The largest gene is 2.4 million bases! The total number of genes is estimated at 30,000 (much lower than original estimates and lower than that of some plant species). 99.9% of bases are exactly the same in all people! 50% of the genes we still dont know what they are for Junk DNA are repetitive sequences in our DNA which do not code for proteins compose approximately 50% of the human genome. A trend has been discovered that Human are not producing as many Junk DNA sequences as before.

The Human Genome Project

How big is it?

An analogy to the human genome is that of a book that is:

Over one billion words long!

1 page 1000 letters:1 book 1000 pages- then needs 3300 books
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The Human Genome Project

What do you do with this information?
Thats where the HGP comes in: Find what regions of the Genome are actually used by the body. These are so called coding regions There are also exons and introns And repeats

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The Human Genome Project

How much do we use?

Less than 2% of the genome codes for proteins.
Repeated sequences that do not code for proteins ("junk DNA") o 50% of the human genome.

Repetitive sequences o no direct functions,

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The Human Genome Project

What is next?

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The Human Genome Project

HGP the base for all the rest

The completion of the HGP has opened new possibilities in biology and medicine

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The Human Genome Project

What can the HGP be useful for?
epigenetics genetic regulation investigating genetic diseases

personalized medicine
genetic engineering

genomes as personal ID -> forensics other-omics ...

genomics, proteomics, interactomics,

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The Human Genome Project

Other genomes comparative genomics
Many more genomes were sequenced:
o Human o Mouse o Chimpanzy ohuman pathogens
Completed Prokaryotic Eukaryotic Archea 554 76 49 On going... 1380 878 57

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 Comparative Genomics
Analyzing DNA sequence patterns of humans and wellstudied model organisms side-byside. Most powerful strategy for identifying human genes and interpreting their function.

The Human Genome Project

Epigenetics:
The structure of chromatin (closed heterochromatin
or open euchromatin) can influence the expression of genes The histone modification code Regulation of gene expression

Chromatin structure and modifications

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The Human Genome Project

OMIM database
Online Mendelian Inheritance in Man
o Catalogues the genetic diseases of human A step towards the personalized medicine

So far there are ~18250 known genetic disorders

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The Human Genome Project

DNA forensics
DNA can be used as a personal ID o Used in forensics

o Paternity test
o Detection of potential biohazards

o Identification of crime victims

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The Human Genome Project has helped scientists in discovering genes which are associated with disease, mental and physical disorders, and cancer.

Research could provide new effective therapies (e.g. gene therapy) which can treat such conditions However, the task of developing these new therapies and developing the technology necessary to sustain them is crucial.

Ethical, legal and social implications of the Human Genome Project

- fairness in the use of genetic information. - privacy and confidentiality. - psychological impact and stigmatization. - genetic testing. - reproductive issues. - education, standards, and quality control. - commercialization. - conceptual and philosophical implications.

What are the implications of the Human Genome Project specifically to each of these areas?
Some questions to consider: - Fairness and privacy: who should have access to your genetic information? Psychological stigmatization: how does knowing your predisposition to disease affect an individual? Genetic testing: should screening be done when there is no treatment available?

Some other issues: - Reproductive issues: use of genetic information in decision making.
Clinical issues: implementation of standards and quality control measures in testing procedures.