As new technologies allow closer investigation of human genomes, scientists are discovering they vary more among individuals than previously thought, one example being the presence of transposons also known as jumping genes, which a new US study found to be suprisingly prevalent in human genomes and also very active in lung cancer genomes.
Researchers at the University of Maryland (UM) School of Medicine in Baltimore, and colleagues from other research centers in the US, have conducted one of the first investigations of jumping genes, self-replicating bits of DNA that copy a section of genome then insert themselves in another section at a different location. You can read about their findings online in the 25 June issue of the journal Cell.
As soon as scientists mapped the human genome, it was clear that it would vary among individuals, study author Dr Scott E. Devine, an associate professor at UM School of Medicine and a researcher at the school's Institute for Genome Sciences, said in a statement.
Devine explained that variation in the human genome "dictates why people look different from one another, why they have different susceptibilities to diseases and different lifespans."
"In this study, we're looking at transposons that insert themselves in new places in various genomes and disrupt the blueprint," he added.
To illustrate why it matters that we find out more about transposons, Devine likened the genome to an instruction manual for building an aircraft and said "imagine what would happen if you copied the page that describes passenger seats and inserted it into the section that describes jet engines."
"Transposons act something like this: they copy themselves and insert the copies into other areas of the human genome, areas that contain instructions for the complex machine that is the human body," said Devine, who started the study when he was a faculty member at Emory University School of Medicine in Atlanta.
"These areas and the instructions they contain may then become corrupted and hard to understand. This, in turn, can alter human traits or even cause human diseases," he explained.
Because transposons replicate themselves, it suggests that offspring have more of them in their genomes than their parents.
"If you have a child, the child could have one or more new copies of these transposons that you don't have," said Devine.
This is the feature that he and his colleagues investigated using new, next generation sequencing and informatics technologies that they had developed.
For this study they examined the genomes of 76 people and found transposons were surprisingly prevalent; they also found they were very active in lung cancer genomes.
Some transposons don't seem to have a serious impact on the human genome, but several dozen have been found that have caused enough disruption to human genes to cause disease.
"We think this is just the tip of the iceberg," said Devine.
In their Cell paper, the researchers describe how their new technologies enabled them to detect insertions of two abundant classes of transposons called Alu and L1, that current technologies are not capable of detecting, and show how such insertions are abundant in human populations.
They wrote that genome-wide analysis suggests that "altered DNA methylation" may be the reason for the high levels of "somatic L1" transposon insertions in lung cancer genomes.
They concluded that:
"Our data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases."
The transposons they found in lung cancer tumors have never been seen before and could be important for cancer research, said Devine, who suggested the jumping genes could actually be driving cancer or tumor progression.
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