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Genetic instability

Genetic instability manifests itself as the accumulation of mutants in a population. It is a potential problem in most industrial processes as low-producing mutants are likely to outgrow the high-producing parent strain. Careful control of strain storage and inoculum preparation can limit the effects of instability. It is probable that genetic instability during scale-up is often not recognised. Detection of instability and optimisation for stability in parallel to physiological optimisation is likely to give improved yields. The type of genetic instability encountered and its detection depends on the type of organism. Both point mutations and DNA rearrangements may occur. The stability of plasmid-carrying strains depends on avoiding both segregational and structural instability. Southern blottings and PFGE can be useful for bacteria, yeast and fungi. FISH methods are important for mammalian cell cultures where changes in chromosome number and chromosome rearrangements often occur. In some cases epigenetic effects may play an important rôle in stability of cultures. Achieving and proving culture stability is an essential step in complying with GMP regulations.

mutation, selection, scale-up, strain degeneration

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