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SVA - structural and functional characterization of a composite primate specific retrotransposon

Applicant Professor Dr. Gerald G. Schumann, since 9/2005
Subject Area Developmental Biology
Term from 2005 to 2009
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 16686508
 
Non-LTR retrotransposons constitute approximately 30% of the human genome. Functional copies of the autonomous non-LTR retrotransposon LINE-1 (L1) encode the protein machinery that is required for their own propagation as well as for the trans mobilization of the non-autonomous Alu elements. An additional group of non-autonomous retrotransposons, are the SVA elements, comprising ~2500-3000 copies per haploid genome. SVAs are unusual composite elements consisting of a SINE-R moiety (¿Short Interspersed Nuclear Element of Retroviral Origin¿), a VNTR region (¿Variable Number of Tandem Repeats¿) and an Alu-homology region. SVAs have been implicated in the generation of a number of human hereditary diseases and display a high level of insertion/deletion polymorphisms, but have barely been characterized so far. Also, the mechanism of SVA mobilization has not been elucidated. One focus of our planned projects is to investigate the mechanism of SVA mobilization. We want to test the hypothesis of SVA trans mobilization by L1-encoded proteins. We are planning to identify SVA-encoded structural features as well as possible host-encoded factors that are involved in SVA retrotransposition. As transcription of SVAs is a crucial prerequisite for their retrotransposition we intend to characterize its regulation. Our second goal is to establish the phylogenetic origin of this composite retrotransposon. This is of special interest since the SVA- encoded SINE-R part was reported to be specific for the hominoid lineage, while the remaining constituents of the composite element are already present earlier in primate evolution. The third goal is to perform a genome-wide analysis of SVA elements to study development, evolution and expansion of this active class of retrotransposons that is shaping the human genome.
DFG Programme Research Grants
Ehemalige Antragstellerin Dr. Annette Damert, until 9/2005
 
 

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