Spontaneous and induced mutatioins caused by the action of a mutagenic agent are modulated by multiple factors. Several \i Drosophila melangoaster\i0 strains showing a great genetic instability and individuals with high frequency of somatic mutation have been described. In order to continue the work carried out by our group during the last few years (included in the projects SAF92-0525 and SAF94-0697 of the CICYT) we attempt to study in depth two relevant factors in determining mutation susceptibility: the presence of transposable elements and deficient DNA repair mechanisms. A great variety of factors may cause the spontaneous or induced reversion of mutants characterized by the presence of retrotransposons. A molecular analysis that we carried out on revertants of this sort of \i Drosophila melanogaster\i0 mutants obtained by chemical and physical treatments show the significant role of \i loci\i0 modifier. Therefore our aim is to carry out a thorough study of such \i loci\i0 as well as other mechanisms involved in the reversion of insertional mutants. On the other hand, the instability of simple repeated sequences, characteristic from many human genetic diseases including some cancers, may be due to mismatch repair deficiency. Such mechanism has been poorly studied in eukariotes. We attempt to apply the AP-PCR technique to the study, characterize and identify \i D. melanogaster\i0 mutants with these mechanisms. This study will be completec with the analysis of instability of defined microsatellites by means of PCR and the isolation of genes concerned with mismatch repair using degenerate primers with consensus sequences from these genes.
|Effective start/end date||1/12/97 → 1/12/00|
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