A new genetic screening process has helped researchers understand the genetic causes of cancer, such as how mutations accumulated in a person’s life can cause leukemia.

The study shows that by comparing a person’s own DNA to that of their cancerous cells, researchers can find DNA mutations that may have led to abnormal cell growth, or cancer.

After sequencing a single leukemia patient’s healthy and cancerous DNA, researchers at Washington University School of Medicine in St. Louis were able to pinpoint several mutations out of hundreds that appeared likely to have contributed to his cancer’s development. He is the second patient with acute myeloid leukemia (AML) to have his entire genome and that of his cancerous tissue fully sequenced, rather than just the portions that are known to be prone to cancer-causing mutations.

“If we only look at genes with known or suspected links to cancer, we’ll miss many mutations that are potentially relevant,” co-author Richard Wilson said in statement.

The study by Mardis et al., published in The New England Journal of Medicine, identified a total of 750 mutations in the patient’s AML genome. Most of them proved irrelevant, but 64 were likely to be cancer-related. Two previously known mutations were newly linked to leukemia.

Timothy Lay, senior author of the study, explained in a statement that most patients with this type of leukemia are treated similarly, at least in the beginning. This study’s patient, for example, received various chemotherapy drugs. Defining cancer mutations could help determine which patients need aggressive treatment, such as a stem cell transplant, and which could be effectively treated with less intense therapies.

Personalized sequencing of entire cancer genomes is possible now because the accuracy and cost of genome sequencing technology has dramatically improved. This study took only a few months at one-third the cost of the first AML patient, who was sequenced only one year ago.

To date 350 cancer mutations are known, but thousands of cancer genomes will need to be screened to truly explain the genetic basis for cancer. This information could be used not just to guide physicians to the most effective treatment, but also to inform patients about their prognosis.

But do patients even want to know?

A recent study published in the Journal of Genetic Counseling suggests they do. Researchers found that 98 of 99 patients with ocular melanoma, a rare, untreatable eye cancer, said they wanted to know if their cancer had a genetic marker that gave them a 50 percent chance of dying within five years. Patients were relieved when the risk was low, but even when the risk was high they were enabled to plan financially and make the most of their time alive.

This very personalized medicine will continue to be driven by improved diagnostic testing, finding more predictive disease markers, and new therapies directed at cancer-specific mutations, James Downing wrote in a recent editorial published this month in The New England Journal of Medicine. He believes this technology will likely be used clinically long before we have a complete knowledge of cancer genes.

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More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. Scientists know that many of the characteristic symptoms of Parkinson’s — tremors, rigid muscles and movement problems — can be traced back to the loss of dopamine-producing brain cells.

But what researchers don’t fully understand is why these cells are damaged in the first place. There are no clear environmental triggers for Parkinson’s, and in most people with the disease genetics doesn’t seem to play a large role either. It could even be that Parkinson’s is really a number of different diseases, all of which lead to the same end result.

Previous research has ruled out genetics as a major contributor to Parkinson’s risk; it is estimated to play a role in fewer than 10% of cases. But piecing together the genetics of Parkinson’s is an active and promising field, because what scientists learn from that minority of cases could improve their understanding of the disease generally. The holy grail would be to pin down all the ways genes can interact with the environment to produce the symptoms of Parkinson’s.

23andMe is working with the Michael J. Fox Foundation, the Parkinson’s Institute and patients from around the world partly because we want to give individuals with Parkinson’s access to their own genetic data. At the same time, we want to join the continuing quest for those genetic and environmental factors that underlie Parkinson’s disease by combining genetic data from our community with members’ responses to surveys about their health.

By far the most common known genetic cause of Parkinson’s disease is the G2019S mutation, which occurs in a gene called LRRK2. While the average person has a 1-2% chance of developing Parkinson’s, the risk for someone with the G2019S mutation is much higher and increases with age. One recent study found that a person who inherits this mutation from either parent has a 28% chance of developing Parkinson’s by the age of 59, 51% by the age of 69 and 74% by the age of 79.

Even though it is the most common known genetic cause of Parkinson’s disease, the G2019S mutation is responsible for only a small fraction of all cases worldwide — about one or two in a hundred. But in some ethnic groups it is a much more frequent cause of the condition. According to published research, up to 40% of people of North African Arab ancestry and 20% of Ashkenazi Jewish people with Parkinson’s have this mutation.

Another mutation in the LRRK2 gene, referred to as G2385R, has been associated with Parkinson’s disease in several East Asian populations. Analyses of the combined results from several studies indicate that people who inherit this mutation from either parent are at two to three times greater odds of developing Parkinson’s than those who do not carry the mutation. Approximately 9% of Parkinson’s patients with Asian ancestry carry the G2385R mutation.

(23andMe customers can find out if they carry the LRRK2 G2019S mutation in the Parkinson’s Disease Clinical Report. Customers can also find out if they carry the G2385R mutation using the Parkinson’s Disease: Preliminary Research Report.)

Although people who have at least one copy of the LRRK2 G2019S or G2385R mutation have an increased risk of Parkinson’s disease, a substantial proportion of people with these mutations never develop the disease. Very little is known about the function of the protein made by the LRRK2 gene, and no one knows why many people who carry mutations in this gene don’t develop Parkinson’s disease. Adding to the mystery, among those with these mutations who do develop Parkinson’s, not all have the same symptoms. Interactions of these mutations with unknown environmental factors may be part of the explanation. Continuing research into these gene-environment interactions could yield valuable clues into the causes of Parkinson’s generally.

Mutations in several other genes have also been associated with Parkinson’s disease, but these are extremely rare. Many have been found only in one or two families. 23andMe is not able to detect most of these rare mutations.

Other Parkinson’s mutations:

• As is the case for mutations in LRRK2, a person need only inherit a mutation in the alpha-synuclein gene (SNCA, also known as PARK1 or PARK4) from one parent to be at substantial risk for Parkinson’s disease. The average age for disease onset in people with a disease-causing mutation in this gene is 46. The protein encoded by the alpha-synuclein gene is one of the main components of the protein aggregates found in brain cells of people with Parkinson’s disease.
• Mutations in parkin (PARK2), PINK1 (PARK6) and DJ1 (PARK7) are recessive, which means a person must inherit mutated copies of these genes from both parents in order to develop Parkinson’s (there are rare exceptions). Multiple mutations in each of these genes have been identified; some are extremely rare.
• Parkinson’s disease caused by mutations in parkin, PINK1 or DJ1 usually strikes at a young age. Parkin mutations most often lead to disease onset between the ages of 20 and 40, although some people are younger than 10 or older than 60 when they develop symptoms. PINK1 mutations usually cause Parkinson’s between the ages of 32 and 48. DJ1 mutations are associated with an age of onset between 20 and 40 years of age.

This is an exciting time in the history of Parkinson’s research. The genetic aspects of the disease could reveal information that is invaluable in the ongoing search for new treatments, or even a cure. We invite Parkinson’s patients, their families and friends, and anyone who believes in the power of scientific research to change lives to participate in the 23andMe Parkinson’s disease community. Visit the 23andMe Parkinson’s community page to learn more.

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In this week’s installment of “The Wild Side,” her weekly column in the New York Times, evolutionary biologist Olivia Judson explains that there are many kinds of mutations. Some affect the parts of genes that encode proteins, the molecules that do most of the work in a biological organism. By changing the structure of these functional molecules, these mutations can dramatically affect an organism’s appearance, metabolism or behavior. Mutations in the protein-coding region of the MC1R gene, for example, influence skin, hair, coat and feather color in humans, mice and birds.

Other mutations affect regions of the genome that determine where, when or how much of a protein is produced. These regulatory mutations can cause effects just as dramatic as the functional ones that alter protein structures. For example, a mutation in a genetic switch that controls the LCT gene allows many people – usually those from cultures where raw milk is a regular part of the diet – to digest the milk sugar lactose as adults. Until relatively recently in human (pre)history, that gene was always turned off after infancy. In most of the world’s people, it still is today.

It will take decades of research to understand how these regulatory mutations influence our biology; Judson guesses they play a major role in differentiating us from other species. And closer to the mission of 23andMe, they probably play a big role in differentiating us from one another as well.

So next time you hear the word “mutation,” don’t think of three-eyed fire-breathing lizard-men – think of yourself.

Illustration by Derek Grime/istockphoto.

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