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HUMAN GENOME PROJECT

Carol Zubiría for SCW 2012-13

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Introduction

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

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First mapped and sequenced: from 1990 to 2003.

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The Human Genome Project (HGP) international initiative

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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.

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Introduction

Like 200 yellow pages books.

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What was the Human Genome Project?

  • HGP aim: sequence the entire human genome and provide the data free to the world.

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  • First major global collaboration of its kind and the largest biological research project ever undertaken, involving thousands of staff in institutes across the globe.

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  • By assigning different portions of the genome to different research groups in a coordinated and

efficient way, the HGP researchers were able to overcome this challenge.

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What was the Human Genome Project?

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Who took part in the project?

Twenty institutes from six different countries

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

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  • 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

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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).

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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.

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How was the human genome sequenced?

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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.

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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.

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What happened after the HGP was finished?

  • Officially finished.

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  • Research continues on the human reference sequence.

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  • Filling in the “gaps” in the sequence.

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  • SNPs (single nucleotide polymorphisms): Genetic variation differences in single bases.

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What happened after the HGP was finished?

  • HapMap project: 3 year → chart the patterns of genetic variation common in the world’s population.

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  • Results 2005 simplify studies to understand how genetic variation contributes to health and disease.

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1000 Genomes Project

  • International research consortium.
  • Launched in January 2008.

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  • 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.

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Genome sequencing Evolution

  • HGP 13 years Billions $

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  • Watson 2007 4 months $1M

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  • Helicos 2009 1 month $ 48.000

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  • Now 1 or 2 weeks 6.000 €

€

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Genome sequencing NOW

How are genes activated?

Genes regulation by regulatory regions.

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8.4 M (10 to 20 letters) identified.

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Variations in regulatory regions: high risk diseases.

Gene therapy