Download Review-6-Epistasis-and-Pathway

Epistasis and Pathway Building
Epistasis- when the phenotype of one mutation masks the phenotype of another.
-The gene whose mutations is being expressed is epistatic to the gene whose phenotype is being
masked.
How does epitasis occur? How can we build pathways from epistatic analysis? (For these examples,
assume all mutations are loss of function).
1) Precursor- product (often biosynthetic pathways)
precursor---------- intermediate----------product
gene A
gene B
-gene A mutation leads to buildup of precursor
-gene B mutation leads to buildup of intermediate
-gene A and B mutations lead to a buildup of precursor.
-gene A epistatic to gene B and is upstream of gene B.
2) Regulatory pathways (often signaling or transcription cascades):
Phenotype A --------|Phenotype B ------ phenotype C
Gene 1
Gene 2
-mutations in gene 1 lead to phenotype A.
-mutations in gene 2 lead to phenotype B.
-mutations in gene 1 and gene 2 lead to phenotype B.
Gene 2 is epistatic to gene 1 and is downstream of gene 1.
How do we tell positive ( ) from negative ( --| )regulation?
-
Single mutations with opposite effects often signify negative regulation.
Single mutations with different effects that are not opposite often signify positive regulation.
Parallel pathways- a complication to epistatic analysis.
- null mutations that are not 100% penetrant, such that each mutation partially affects the phenotype.
A B
C
D E
Example problem:
dpy-1 and dpy-4 mutants are all fat and “dumpy”, so are the double mutants. Dau-2 and dau-3 are are
all thin and “dauer”, so are the double mutants. What can you infer about the relationship between the
genes from the following epistatic analysis:
dpy-1 and dau-3= thin
dpy-4 and dau-2= fat
dpy-4 and dau-3= thin