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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).
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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).
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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.
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