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Lecture 15

Lecture 15 - Pushing the Frontiers of Science: The Human Genome Project

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University of Toronto Mississauga
Esteban Parra

Pushing the Frontiers of Science: The Human Genome Project th During the 20 Century - There have been several key achievements in the field of genetics and molecular biology - First quarter of the century: the discovery of the cellular basis of heredity, the chromosomes. - Second quarter of the century: the discovery of the molecular basis of heredity, the DNA double helix. - Third quarter of the century: the elucidation of the informational basis of heredity, and the invention of recombinant DNAtechnologies. The Beginning of the 21th Century - Will be remembered by one of the most important scientific achievements ever undertaken by humankind: - The completion of the Human Genome Project - In this lecture, we will review briefly how this happened, and we will discuss its relevance. Some Important Background - Two major events happened in the 1970s that set the foundation of future genetic research.. - The development of recombinant-DNAtechnology (Paul Berg was a key player). It became possible to manipulate genes: the origin of genetic engineering! o Possible to manipulate genes; capture genes and put them into other species o Asilomar – conference to do recombinant DNAwork; decided many things like containment levels (levels of security); decided to band certain experiments (pathogenic organisms) - The discovery of DNAsequencing methods, independently by Walter Gilbert and Fred Sanger. Decoding life was finally possible! o This method was used in the human genome project (as it was simpler to use) Origins of the Idea - In the early 1980s, the complete sequences of some small viruses, and the human mitochondrion were already available. - Interest was growing for the construction of genetic maps to locate disease genes and physical maps to understand the order of nucleotides in the genome of diverse species. - In the mid 1980s, scientists began to consider seriously the possibility of sequencing the Human Genome. The Start - In 1988, a panel of the National Research Council of the US endorsed the idea of sequencing the human genome. This was pivotal for the start of the “Human Genome Project”. - In the US, the Department of Energy (DOE), and the National Institutes of Health (NIH) became major players in the project. The Human Genome Project was launched on 1990. - Other institutes from England, France and Japan later became involved in the project. Remember Him? - James Watson was appointed director of the National Center of Human Genome Research (NCHGR/NIH). - Important decisions were made at this time, such as devoting 3% of the budget to social and ethical aspects ARelatively “Slow” Beginning - The Human Genome Project progressed slowly for some years. Pilot projects were launched to demonstrate the feasibility of large-scale and cost-effective sequencing. - Akey decision was made in 1996: rapid release of the sequencing data to the public domain. This was considered important to maximize benefits to society. o The most important o Anyone including you and me, and load sequence data 1998:ACritical Year - In 1998 Craig Venter, a scientist who previously had sequenced for the first time a free- living organism (H. influenzae, 1995), announced plans to set up a private company to decode the Human Genome in record time, using a different approach. Celera Genomics was born. o His goal was to sequence the entire human genome o This was a private effort (not a public effort) o He collaborated with one of the major manufactory of sequencers Changing Gear - In 1999, the publicly supported project moved into full-scale production. This boost was driven in part by what was learned in the previous pilot projects and the threat posed by Celera. - Celera continued its massive sequencing effort, and published in 2000 the complete genome of the fruit fly, Drosophila Melanogaster. Two DifferentApproaches to get the Sequence - Note: Celera could use the HGP sequence data freely available to the public to improve the genome assembly. 2001: The First Draft of the Human Genome - In 2000, the HGP consortium and Celera jointly announced in the White House working drafts of the Human Genome. - In 2001, the working drafts were published, in Nature (HGP) and Science (Celera). The Landscape of the Human Genome - The publication of the working drafts of the Human Genome provided an immense amount of information to the scientific community. The draft covered around 90% of the gene-rich euchromatic portion of the human genome. - We will review the main details of the genomic landscape in the next lecture. 2003: The Completion of the Human Genome Project - The Human Genome Project was officially completed inApril 2003, coinciding with the 50 anniversary of the “double helix”. The original goals were widely surpassed. Next Generation Sequencing Technologies - The Human Genome Project was completed in 2003, with an estimated cost of $2.7 billion. - Since then, there have been dramatic advances in sequencing technologies, and now the cost of sequencing genomes is down to only thousands of dollars per genome! The Impact of the Human Genome Project - The impact of the Human Genome Project will be enormous. The end of the HGP is just the beginning of a new era of discoveries in multiple areas of science. 1 - The rest of the lecture will provide a summary of some fields in which the HGP has already had a major impact, but for which major challenges still remain. Biology - (1) Identifying the structure and function of genomes o Genomic structure has turned out to be extraordinarily complex (more details in next lecture), and the function of the genome is poorly understood. Some of the things that remain to be done are: o Precise Identification of the full complement of human genes (~25,000). o Better understa
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