August 16, 2010

Scientists identify DNA that may contribute to uniqueness

Building on a tool that they developed in yeast four years ago, researchers at the Johns Hopkins University School of Medicine scanned the human genome and discovered what they believe is the reason people have such a variety of physical traits and disease risks.

In a report published in the June 25 issue of Cell, the team identified a near-complete catalog of the DNA segments that copy themselves, move around in and insert themselves here and there in our genome. The insertion locations of these movable segments—transposons—in each individual’s genome help determine why some are short or tall, blond or brunette and more or less likely to have cancer or heart disease. The Johns Hopkins researchers say that tracking the locations of transposons in people with specific diseases might lead to the discovery of new disease genes or mutations.

Using their specialized “chip” with DNA spots that contain all the DNA sequences that appear in the genome, researchers applied human DNA from 15 unrelated people. The team compared transposon sites first identified in the original published human “index” genome and found approximately 100 new transposon sites in each person screened.

“We were surprised by how many novel insertions we were able to find,” said Jef Boeke, a professor of molecular biology and genetics, co-director of the High Throughput Biology Center of the Institute for Basic Biomedical Sciences and an author on the article. “A single microarray experiment was able to reveal such a large number of new insertions that no one had ever reported before. The discovery taught us that these transposons are much more active than we had guessed.”

Each of the 15 DNA samples used in the study was purified from blood cells before being applied to a DNA chip. Transposons stick to spots on the DNA chip corresponding to where they’re normally found in the genome, letting the researchers locate new ones.

Boeke’s group invented the transposon chip in 2006 for use in yeast; Kathleen Burns, now an assistant professor of pathology at Johns Hopkins, first got the chip to work with human DNA. “The human genome is much larger and more complex, and there are lots of look-alike DNAs that are not actively moving but are similar to the transposons that we were interested in,” Burns said. The trick, she said, was to modify how the scientists copied the DNA before it was applied over the chip. The team was able to copy DNA from the transposons of interest, which have just three different genetic code letters than other look-alike DNA segments.

“We’ve known that genomes aren’t static places, but we didn’t know how many transposons there are in each one of us,” Burns said. “We didn’t know how often a child is born with a new one that isn’t found in either parent, and we didn’t know if these DNAs were moving around in diseases like cancer. Now we have a tool for answering these questions. This adds a whole dimension to how we look at our DNA.”

Authors of the study, in addition to Boeke and Burns, are Lisa Cheng-Ran Huang, Anna Schneider, Yunqi Lu, Tejasvi Niranjan, Peilin Shen, Matoya Robinson, Jared Steranka, David Valle, Curt Civin, Tao Wang, Sarah Wheelan and Hongkai Ji, all from Johns Hopkins.

Funding for this research was provided by grants from the National Cancer Institute, National Human Genome Research Institute, Brain Science Institute at Johns Hopkins School of Medicine and Goldhirsh Foundation, and by a Career Award for Medical Scientists from the Burroughs Wellcome Foundation.

Related websites

Boeke lab:


High Throughput Biology Center: