Haig Kazazian, M.D.
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Baltimore, MD 21205
Over the past 22 years, the Kazazian lab has concentrated its efforts mainly on the biology of LINE-1 (L1) retrotransposons in human beings and mice. Retrotransposons are pieces of genomic DNA that have the ability to duplicate themselves and insert into a new genomic location. Over the years, we have found a number of human and mouse L1s insertions causing disease, including hemophilia A and muscular dystrophy. After finding the first such disease-causing insertions (1), we isolated the precursor (2) and devised a cell culture assay for retrotransposition (3). Using this assay, we have found that the average human diploid genome has 80-100 active L1 retrotransposons, but that most of the activity resides in a handful of very active or “hot” elements. We have also observed retrotransposition of human and mouse L1 elements in transgenic mice and rats, and found that most retrotransposition occurs not in germ cells but in the early embryo, resulting in somatic mosaicism (Reviewed in 4). Our most recent work utilizes the power of next generation DNA sequencing to locate essentially all human-specific L1s in any genome (5). This technique opens up the ability to answer many questions about L1 biology, including the frequency of somatic mosaicism in various human tissues and the role of L1 insertions in complex human disease, such as cancer and mental disorders.