"The basic problem was that a new insertion can be anywhere within three billion base pairs how do you find it compared to all the other ones?" Devine says.
Ninety-seven percent of genomes the team surveyed had at least one rare insertion of the L1 variety of transposon that was present in only a single human in the study, and some genomes had several. Since the study surveyed 76 genomes, "rare" insertions could still be shared by large groups consisting of thousands of people. Rare insertions corresponded to the most recent transposons, which are less likely to have their jumping abilities impaired by other types of mutations.
Devine's team also showed that transposons frequently jump to new locations during the process of tumor formation. Surveying 20 lung tumors and comparing their genomes against the normal tissues they came from, the team found that six tumors had new transposon insertions that were not present in the normal adjacent tissues.
"This indicates that transposons are jumping in tumors and are generating a new kind of genomic instability," Devine says.
Transposons can inactivate tumor suppressor genes and can facilitate rearrangements that involve large stretches of chromosomes. Geneticists have already identified many transposons that interrupt genes and cause human diseases, including neurofibromatosis, hemophilia and breast cancer.
Scientists believe a process called methylation, which silences genes during differentiationalso shuts off transposons' ability to jump. Analyzing the patterns of mutations in the lung tumors suggested that during tumor formation, modified methylation patterns may be allowing transposons to re-awaken, Devine says.
|Contact: Vince Dollard|