Download Variation in Gene Expression

Pleiotropic Effects and Lethal Genes
During the first years after the rediscovery of Mendel's laws, a number of experiments
were performed that gave results that at first glance did not coincide with the laws. A
cross was made between a yellow-coated mouse and a mouse with a gray coat. The
gray- coated mouse was extensively inbred and therefore was considered to be pure
bred.
What allelic relationship do we have here? We know that the gray mouse is
homozygous (because it is a pure line). If gray coat was dominant then we would see all
gray mice. Since we obtain both yellow and gray mice, yellow must be dominant to gray.
Gene Symbols: gray = y
yellow = Y
From the above discussion, the genotype of the gray mouse must be yy. What is the
genotype of the yellow mouse? If the mouse was homozygous we would not see any
gray mice from the cross, therefore the genotype must be heterozygous or Yy.
Next a cross was made between two yellow mice. The cross Yy x Yy was given a ratio
of 2 yellow to 1 gray mice. How can this result be explained? Expected Punnett
Square
Female Gametes
Y
Y
Male
Gametes y
y
YY
Yy
(yellow) (yellow)
Yy
(yellow)
yy
(gray)
As we can see, we should get a 3:1 ratio of yellow to gray mice, so some genotype
could be absent from the progeny. All testcross data with the yellow mice give a 1:1
ratio. This ratio is typical of what is seen with heterozygous individuals. Therefore, all of
the yellow mice are heterozygous Yy. Somehow the YY genotype is lethal. The 2:1
ratio is the typical ratio for a lethal gene.
Lethal Gene - a gene that leads to the death of an individual; these can be either
dominant or recessive in nature. For example, people with Marfan syndrome may be
tall, thin, have long legs, arms and fingers, and may be nearsighted. Their connective
tissue is defective. If unrepaired, the connective tissue surrounding the aorta will
eventually rupture and kill the person. All of these characteristics are due to a single
gene.
Pleiotropic gene - a gene that affects more than one phenotype.
In this example the gene that causes yellowing of the coat also affects viability and is
termed a pleiotropic gene. An important question is how can a gene controlling coat
color cause death in an organism? Possibly in a single dose the allele causes a
yellowing of the coat, but when expressed in two doses, the gene product kills the
animal. Thus, this gene actually has an effect on two phenotypes.
Variation in Gene Expression
Not all traits are expressed 100% of the time even though the allele is present. For
example the dominant allele P produces polydactyly in humans, a trait that is
characterized by extra toes and/or fingers. Two normal appearing adults have been
known to mate and produce offspring that express polydactyly. Thus one parent must
carry at least one dominant allele (P allele) and its genotype is probably Pp. This parent
with the Pp genotype exhibits reduced penetrance for the P allele.
Penetrance - the frequency of expression of an allele when it is present in the genotype
of the organism (if 9/10 of individuals carrying an allele express the trait, the trait is said
to be 90% penetrant)
Not all phenotypes that are expressed are manifested to the same degree. For
polydactyly, an extra digit may occur on one or more appendages, and the digit can be
full size or just a stub. Therefore, when the P allele is present it expresses variable
expressivity.
Expressivity - variation in allelic expression when the allele is penetrant.