Salk Institute

Technologies Available for Licensing

A New Diagnostic Assay: Measuring Retrotransposition in Man

Inventors: Fred H. Gage, Nicole Coufal, Mike McConnell, Alysson Muotri, Maria C.N. Marchetto
Potential Uses: CNS, Diagnostics, Gene Expression, Research Tool, Stem Cells

L1 retrotransposition in human neural progenitor cells

Assay for determining retrotransposition. To determine whether human NPCs can support L1 retrotransposition, we transfected human fetal brain stem cells (hCNS-SCns) with an expression construct containing a retrotransposition-competent human L1 (RC-L1) driven from its native promoter (L1RP) Green cells (ie, GFP pos.) only arise if retrotransposition occurs.

Retrotransposons make up roughly 40% of the mammalian genome and have played an important role in genome evolution. Their prevalence in genomes reflects a delicate balance between their further expansion and the restraint imposed by the host. A major group of retrotransposons is LINEs (long interspersed nucleotide elements). LINEs occupy about 18% of the human genome and can be traced to 65 known human diseases.

In the interest of understanding the role and activity of these mobile DNA segments, we developed assays to detect LINE transposition and used it to characterize the main lineages of the human nervous system as well as to examine brain tissue. Using these assays we show that LINE can retrotranspose during early development, and in select somatic cells. We also showed a statistically significant increase in LINE content in the hippocampus when compared to heart and liver samples from the same individual. Using this highly efficient method to measure Line retrotransposition in tissue samples and single cells will allow researchers to gain a more complete understanding of the role of retrotransposons in man, with a focus on the etiology of disease and diagnostics.

Salk No: S09023
Patent Status: U.S. Patent Application filed August 2009
Publications: N. G. Coufal, J. L. Garcia-Perez, G. E. Peng, G. W. Yeo, Y. Mu, M. T. Lovci, M. Morell, K. S, O'Shea, J. V. Moran & Fred H. Gage. L1 retrotransposition in human neural progenitor cells. Nature: Online Aug 5, 2009. Supplement
Press Release: "Jumping genes" create diversity in human brain cells, offering clues to evolutionary and neurological disease
License Terms: Exclusive, Partially Exclusive, Nonexclusive license negotiable
Contact: Michelle Booden, Ph.D., Director of Licensing, 858.453.4100 x1612, mbooden@salk.edu

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