How do genes interact and does the IMPC plan to inactivate two or more genes at a time?

The two related questions below have recently been sent in to our Reddit and Twitter accounts. The IMPC chair Steve Brown has provided the following answers.

Something I’ve wondered about many times is: do genes all have non-related, specific functions or do they inter-react in some fashion such that you’d have to understand the relationship of each in relation to all of the others to predict the outcome of a modification?

Genes for the most part do not have one-to-one functions. That is a specific gene generally does not impact on one particular aspect of our physiology, biochemistry or development. Genes have multiple functions (a phenomenon called pleiotropy). This arises for a number of reasons:

  1. some genes regulate the expression of other genes – genes are often linked together in networks that are under joint control
  2. genes produce proteins that often act together in protein complexes, so that a modification in one gene can have a bearing on the action of proteins produced by other genes.
  3. Genes produce proteins that are part of the same pathway e.g. a group of genes that produce a number of enzymes that together are a set of enzymes for producing an important metabolite
  4. Groups of genes can work together during development to establish positional information which is important for example to determine limb development, digit formation, craniofacial morphology

One of the most complex challenges for genetics is to determine not only the individual, immediate role of a genes – its basic core function – but how it works with other genes, and how the protein that a gene produces interacts with other proteins. Determining these complex networks is the next stage for geneticists after IMPC has determined basic information on each gene by introducing a mutation into every gene in the genome.

Is there a plan to KO (inactivate) combinations of 2 or more genes?

As IMPC moves to produce a KO for every gene in the mouse genome, it will be possible to combine them together to generate KOs of 2 or more genes, further exploring how the genome works and its role in disease.


More information on the IMPC and its aims can be found in the video below or by following this link: What is the International Mouse Phenotyping Consortium?

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