4 September 2012
4 - 5pm
Venue: Ground Floor Seminar Room (G010), UniServices House, 70 Symonds Street, Auckland
A Bioengineering research seminar by Dr Jessie Jacobsen, Neurological Foundation of New Zealand Repatriation Fellow, Centre for Brain Research, School of Biological Sciences
The introduction of synthetic pieces of DNA or ‘transgenes’ into model organisms or cultured cells is a fundamental genetic tool widely used in biological research. However, for most of these transgenic models, there is little known about how and where these transgenes insert into the host DNA and the effect this integration event can have on the surrounding host DNA. Using three different DNA sequencing approaches, we characterized the transgene sequence and insertion site in the DNA of seven Huntington’s disease (HD) animal models. Our analyses revealed that the insertion of the transgene caused extensive rearrangement to the DNA, altering both the transgene itself, and the host DNA adjacent to the insertion site of the transgene. These analyses indicate that the site of integration and resultant rearrangement of the host DNA are all factors that can confound interpretation in transgenic model experiments. The transgene-mediated rearrangements also mirror complex DNA rearrangements being uncovered in some human genetic disorders, and might provide insights into how the human genome (genes and non-coding information) can dynamically remodel itself to produce rearrangements that contribute to altered human development and disease.