Haig Kazazian, M.D.Kazazian_Lab_Portrait_(Paul McGuirk Photography)_200x200

Professor of Human Genetics

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Contact Information

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Baltimore, MD 21205

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410-502-6660 (Office)

Research Interests

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.

 

Selected Publications

  • Kazazian HH, Jr., Wong C, Youssoufian H, Scott AF, Phillips D, and Antonarakis SE: A novel mechanism of mutation in man: Hemophilia A due to de novo insertion of L1 sequences.  Nature, 332:164-166, 1988.

  • Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH, Jr.  Isolation of an active human transposable element.  Science 254:1805-1808, 1991.

  • Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, and Kazazian HH, Jr.  High frequency retrotransposition in cultured mammalian cells.  Cell 87:917-927, 1996.

  • Goodier JL and Kazazian HH Jr. Retrotransposition revisited: the rehabilitation and restraint of parasites.  Cell 135:23-35, 2008 (Invited and peer-reviewed review).

  • Ewing, AD Kazazian, HH, Jr.High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes. Genome Research 20:1262-1270, 2010.

  • Ewing AD and Kazazian HH Jr. Whole-genome resequencing allows detection of many rare  LINE-1 insertion alleles in humans. Genome Research 21:985-90, 2011. 

  • Hancks DC, Goodier JL, Mandal PK, Cheung L, and Kazazian HH, Jr. Retrotransposition of the hominoid retrotransposon SVA by human L1 in cultured cells. Human Molecular Genetics 20:3386-400, 2011.

  • SolyomS, Ewing AD, Hancks DC, Takeshima Y, Awano H, Matsuo M, and Kazazian HH, Jr. Pathogenic orphan transduction created by a non-reference LINE-1 retrotransposon. Human Mutation 33:369-71, 2012.

  • Hancks DC, and Kazazian HH Jr. Mammalian retrotransposons in health and disease. Current Opinion in Genetics and Development, Epub March 8, 2012.


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