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Functional Gene Identification

The recent rapid sequence analysis of the human, fly, plant and microbial genomes identifies many candidate genes, the majority of unknown function. The functional analysis of whole genomes is now central to the development of new medicines and diagnostics for the treatment of human and animal diseases and new pesticides for agricultural applications.

Gene Transposition in Mammals

The Minos transposon can be used to randomly tag genes for functional gene identification in mammalian cell-lines, and will also mobilise and transpose genetic elements in somatic cells in mice (see Klinakis et al EMBO Reports (2000), 11, 416-421; Zagoraiou et al PNAS (2001) 98, 11474-11478). Studies demonstrate germ line transposition and insertion within genes in mice ( see Drabek (2003) Genomics 81, 108-111).
 


In Vivo Transposition in the male germ line

Recent work in the laboratory of Professor Grosveld has resulted in the development of a high efficiency male germline transpositon system in mice. This represents a major break through for the study of gene function in mammalian systems and in particular the identification of disease causing genes where the genetics is complex (e.g diseases of the Central Nervous System, Insulin Resistance and Inflammation). 


Southern blot demonstrates transposition in all mouse offspring

Unlike alkylation approaches the use of transposon technology allows the immediate identification of the site of insertion in the genome of progeny where gene insertion has resulted in a change in a measurable phenotype. This means that the technology can now be applied to the study of gene function in rodent models of human disease irrespective of the genetic background, and provides a direct link between “the cause”, an insertional event, and “the effect” a change in a measurable phenotype (biochemical, physical, behavioural etc). 

 

Gene Identification in Drosophila

The value of P element transposon technology for the functional analysis of genes in the fruit fly Drosophila melanogaster is well known. However P element does not insert uniformly across the Drosophila genome. Minos transposes with high efficiency in Drosophila. Analysis of over 100 independent transposition events shows that the Minos transposon inserts at different sites from that of the P element within the drosophila genome with a bias to introns (Savakis – in preparation).

The Minos transposon provides a valuable complement or alternative to P element for functional studies in Drosophila and in other insects, and is particularly suited to studies encompassing gene and promotor trapping.