期刊
CELL
卷 141, 期 7, 页码 1253-U268出版社
CELL PRESS
DOI: 10.1016/j.cell.2010.05.020
关键词
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资金
- American Cancer Society [PF-07-130-01-MGO]
- SUN Microsystems
- National Institute for General Medical Sciences, National Insitutes of Health (NIH) [R01GM078541]
- National Cancer Institute, NIH [R01CA086335, R01CA116804, 1R01CA132065, 5P01CA116676]
- National Human Genome Research Institute, NIH [F32HG004207, R01HG002898]
Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. 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.
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