Learning About the $1,000 Genome

Personalized MedicineAt the recent International Symposium on Human Identification, Kevin Davies, the keynote speaker and author of The $1,000 Genome, entertained attendees with a history of human genome sequencing efforts and discussed ways in which the resulting information has infiltrated our everyday lives. Obviously, there is enough material on the subject to fill a book, but I will describe just a few of the high points of his talk here.

Davies started his talk with a personal story about how he missed an opportunity to work at the University of Leicester, where Alec Jeffreys made his famous discovery of polymorphic microsatellite sequences, which were the basis of DNA-based identification. Davies claims “It was for the best because I would have looked at that smudged autoradiograph and thrown out the first DNA fingerprint, embarrassed to show anyone else due to the low quality of the image”.

He then presented a timeline of human genome sequencing. A few of the highlights include:
1990: The international effort to sequence the human genome, dubbed the Human Genome Project, was officially started and was projected to cost $3 billion (U.S. dollars).
1998: Craig Ventner from Celera Genomics upped the stakes by entering the race to complete the sequence at an estimated cost of $300,000,000.
2003: The National Human Genome Research Institute announced the complete human genome sequence.
2005: The 454 DNA sequencer revolutionized DNA sequencing and substantially reduced costs. The 454 instrument was used to sequence the genome of James Watson, half of the famous Watson and Crick duo who first published a model of the DNA double helix.
2008: Marjolein Kreik in the Netherlands becomes the first woman to have her genome sequenced. Why her? Because her name sounds like “Crick”.
2010: Personal genome sequencing costs $50,000.
2013: The cost to sequence a human genome drops to $5,000. We are not quite at the point of the $1,000 genome (yet). However, to reach that milestone, Davies believes that scientists will need to develop new technologies.

During this time period, the sequencing cost per megabase (Mb) steadily decreased:
September 2001: $5292.39
January 2005: $974.16
April 2008: $15.03
October 2009: $0.78
October 2011: $0.086
Source: www.genome.gov/sequencingcosts/.

How has whole genome sequencing affected our lives today, and what does the future hold? I think we would all agree that genome analysis has had a great impact and has become commonplace. There are constant examples of this, including the use of DNA typing to identify the remains of Richard III, the recent US Supreme Court ruling about DNA collection from people arrested for but not yet convicted of a crime, the use of STR typing to identify dog owners who do not not pick up after their pets and finally the bus drivers in Brisbane Australia who are armed with DNA collection kits to discourage spitting on public buses. However, the example that Davies spent the most time discussing was the link between genome sequencing and personalized medicine.

Now that it has become cost-effective to sequence an entire genome rather than a single gene, Davies predicts that whole genome sequencing will become the standard of medical care (but acknowledges potential obstacles and bottlenecks such as ethical and legal considerations and the ability to process large amounts of data quickly). In his talk, Davies mentions two medical cases where genome sequencing has provided answers and, in one case, a treatment.

In the first few years of his life, Nicholas Volker had to endure over 100 surgeries to treat an autoimmune disease that affects his intestines, with limited success. Desperate for answers, doctors turned to DNA sequencing to try to explain the boy’s mysterious medical condition. Sequencing revealed approximately 16,000 DNA variants, including a cysteine to tyrosine mutation at position 203 of the XIAP gene, which encodes a protein that prevents apoptotic cell death. Detection of this mutation gave doctors hope that an umbilical cord blood transplant would help treat Nic’s conditions and give him the chance at a better life. Two years after his transplant, Nic is nearly indistinguishable from a normal six-year-old boy.

The second example involves Adam Foye. Early in his young life, it became obvious that Adam suffered from some form of myopathy; he missed many of his motor milestones such as lifting his head and did not start walking until 15 months of age. Analysis of 13 genes associated with muscle weakness did not reveal the cause. Adam underwent whole genome sequencing, which uncovered a mutation in the titin gene, which encodes a ~3,700kDa protein important for muscle contraction. Although sequencing revealed the cause and led to a diagnosis of centronuclear myopathy, it has not led to a cure.

These types of cases, where DNA sequencing offers clues to diagnosis and treatment of diseases and genetic disorders, will increase in the future as costs associated with whole genome sequencing continue to decline. Likewise, cases where DNA sequencing is used to gauge an individual’s genetic predisposition to a disease will become more common, allowing preventative measures that may reduce that risk. At some point in the not-too-distant future, the cost of sequencing may be almost negligible compared to the total cost of treating a patient.

Davies’ talk made me realize that we are all very fortunate to live in the age of the $1,000 genome. The benefits range from the seemingly silly (e.g., identifying people who spit on public transportation) to the amazing (e.g., the beginnings of personalized medicine). It’s been only 10 years since the complete human genome was sequenced, and scientists have learned amazing things in that short time. I’m eagerly waiting to see what the next 10 years and beyond brings.

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Terri Sundquist

Terri has worked as a Scientific Communications Specialist at Promega Corporation for more than 13 years, and prior to that, spent more than 5 years solving problems and answering questions as a Promega Technical Services Scientist. She graduated with B.S. degrees in Chemistry and Biology at the University of Wisconsin—River Falls, then earned her M.S. in Molecular Biology from the Mayo Graduate School in Rochester Minnesota.

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