Development of bioinformatics methodologies for analysis and caracterization of LINE-1 retrotransposons from brain tissue related to Rett Syndrome development

Abstract

Long interspersed nuclear elements of type 1 (LINE-1 or L1) belong to the most abundant type of retrotransposon found in the human genome, and it has been shown that these elements are associated with several regulatory factors. In the brain, they may be responsible for the genetic variability between neurons, suggesting that their genome works like a dynamic unity, so that there is a genetic mosaicism among them. Work in this area has provided a broader and deeper understanding of the genetic structure of brain cells, and of some of the genetic disorders associated with brain tissue. Experiments in transgenic mice have revealed, for example, that a reduction in the expression levels of the MeCP2 gene, the Rett's Syndrome causal, is associated with an increase in the expression level of L1 elements, which are copies of an L1 element that is also active in humans (unpublished results). However, it is uncertain how the activity of these L1 elements works, and there are no obvious patterns of reintegration in the genome, and so new studies and experimental approaches are needed in order to genetically characterize this brain disorder and its relationship with retrotransposons. With this in mind, our aim in this project is to construct and apply a set of methodologies based on bioinformatics to analyze genomic L1 retroelements derived from brain tissue. Such an analysis will enable us to characterize and understand the behavior of L1 elements with respect to the occurrence of Rett's syndrome. A further goal is to infer the number and location of somatic in vivo retrotransposition events of L1 elements, and investigate whether or not these events preferentially occur in coding or non coding regions, and if these regions are being transcribed. The results may lead to new experiments to provide insights into how some brain disorders associated with mobile genetic elements, like Rett's Syndrome, may affect the behavior of an individual. (AU)