“When we began the Human Genome Project, we anticipated it would take 15 years to sequence the 3 billion base pairs and identify all the genes,” said Dr. Richard Gibbs, director of the Human Genome Sequencing Center. “We completed it in 13 years in 2003 – coinciding with the 50th anniversary of the publication of the work of Watson and Dr. Francis Crick that described the double helix.
"Today, we give James Watson a DVD containing his personal genome – a project completed in only two months. It demonstrates how far the sequencing technology has come in a short time.”
The $1 million, two-month project is significant because it demonstrates that it will be possible in the future to sequence anyone’s genome. The time and cost will decrease as the technology improves.
“When I conceived the 454 Sequencing(TM) technology, I envisioned making routine individual genome sequencing a reality to help with personal medical care,” said Jonathan Rothberg, founder and former chairman of 454 Life Sciences. “Since Dr. Watson is the co-discoverer of DNA’s structure and a 1962 Nobel Laureate, it is only appropriate to work with him on this ambitious genome sequencing project. This project will pave the way for exploring life at the ultimate level by uncovering what makes each individual unique.”
454 Life Sciences generated the raw sequence data, using DNA extracted from a specimen of blood. Its revolutionary new technique means that there is no need for laborious and expensive up-front bacterial cloning of the DNA. Instead the DNA is directly used in a polymerase chain reaction and fed into a new 1.63 million-well DNA sequencing plate. The sequence data stream into a computer for subsequent analysis.
The HGSC verified the accuracy of the sequence and determined whether it encompassed everything in the genome. This helped validate the new technology developed by 454 Life Sciences that made the project possible.
The HGSC then analyzed the content of the genome and searched for evidence of genes for diseases such as cystic fibrosis or muscular dystrophy. Because these are recessive genes, a person must have two mutated copies to have the disease. Having one copy makes a person a carrier for the disease.
They also looked for gene variants or alleles that can raise the risk of chronic diseases such as those of the heart or kidneys.
The HGSC also managed the process of providing the information to Watson, which included designing an ethical model for providing the data, writing a consent form that covered all the risks and ethical issues involved and obtaining research approvals from BCM boards.
BCM’s strength in genetics, diagnostics and genomics made it a logical partner in the project. For example, BCM has developed gene chips that can evaluate DNA in chromosomes for deletions or additions associated with increased risk of some diseases.
“These gene chips provided independent confirmation that features found in the sequences match those found in other assays,” said Gibbs.
Watson, who chose BCM as the site at which the data transfer will take place, plans to evaluate the information included in the genome and write about its significance to him, his family and the future of genetic medicine at a later time.
“There will be a host of ethical and social questions as we move into the phase of integrating this kind of information into clinical in the future,” said Dr. Amy McGuire, assistant professor of medical ethics at BCM. She has advised on the ethical issues involved in this personal genome effort.
Source: Baylor College of Medicine