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How do geneticist order genes in a process into a biochemical or genetic pathway?

How do geneticist order genes in a process into a biochemical or genetic pathway?

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Expert Solution

A major tool of developmental geneticists is the ordering of genes in functional pathways. AveryandWasserman(1992) have provided a brief theoretical discussion of epistasis analysis; here we explain the more practical aspects of how models of developmental pathways are built in C. elegans.

Epistasis is the masking of the phenotype of one mutant by the phenotype of a mutant in another locus. Hence, epistasis analysis can be used to determine a functional order of action of two genes, regardless of the directness of the interaction. However, epistasis analysis is most informative when the genes analyzed control a common process. Thus, it is important to determine the relationships between the mutations of interest before embarking on the construction of a formal genetic pathway.

Two different kinds of pathways exist . Historically, these have been distinguished as regulatory pathways and assembly or metabolic pathways. As both types of these pathways require "regulation," for the purpose of this chapter we will refer to the classical regulatory pathway as a switch regulation pathway and the classical assembly pathway as a substrate dependent pathway. The switch regulation pathway involves genes or gene products that can be turned "on" or "off". The different states of the genes (or their products) involved this type of pathway determine the outcome of the pathway. Mutations in genes involved in this type of pathway will have two distinct and opposite phenotypes, and will also have the ability to bypass the requirement for upstream genes. The second type of pathway involves a substrate, where an obligate series of sequential steps are required to generate the final outcome; classical examples of this second type of pathway include metabolic pathways and bacteriophage morphogenesis. Mutations in genes involved in the substrate dependent pathway will have phenotypes that suggest a progression of events. Sometimes determining which of the two types of pathways the genes of interest are involved in requires extensive phenotypic analysis of the mutations involved.


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