Multiple Allele Traits

Multiple-Allele Traits
Traits controlled by more than two alleles have multiple alleles. Although any one
person usually has only two alleles for a gene, more than two alleles can exist in
the population's gene pool. Theoretically, any base change will result in a new allele. In
fact, within the human population, it may be safe to say that most human genes have
more than two alleles. Whereas, we think of base changes, or mutations, as resulting in
a new phenotype or disease, many base changes result in alleles that do not cause
significant change in phenotypes. This is common in collagen genes, for example. Type I
and type II collagen are fibrillar proteins composed of a triple helix. As these are
structural proteins found in bone and cartilage, a triple helix adds strength to the matrix
with these proteins. To form a triple helix structure, a glycine residue must be placed at
every third amino acid within the fibrillar segment of the protein. The fibrillar portion of
the protein is composed of Gly-X-Y motif, where X and Y represent two additional amino
acids. As glycine is encoded by four codons: GGG, GGC, GGA, GGU, any change of
sequence in the third position of the codon will not have an effect on the protein
structure. Furthermore some changes in the X and Y positions of the Gly-X-Y motif may
not cause significant phenotypic changes. However, other changes may have significant,
even lethal consequences.
The best characterized example of multiple alleles in humans is the ABO blood groups,
discussed in the Non-Mendelian Inheritance concept. Other human traits determined by
multiple alleles would be hair color, hair texture, eye color, built, physical structures,
etc. Most, if not all of these multiple-allele traits are in traits with very diverse
phenotypic possibilities.
It is easiest to consider situations where each gene affects only one phenotypic
characteristic. However, other situations where genes have other effects are common.
As mentioned above, multiple alleles resulting in multiple phenotypes are not
uncommon.

Pleiotropy
Many genes have multiple phenotypic effects, a property called pleiotropy. Thus, a
new mutation in the gene will affect all the phenotypes/traits associated with the gene
simultaneously. For example, the symptoms associated with sickle-cell disease are due
to pleiotropic effects. Individuals with sickle-cell disease are homozygous for the mutant
allele, resulting in sickle-shaped red blood cells. Because the sickle-shaped red blood
cells deliver less oxygen to the tissues, sickle-cell disease has many pleiotropic effects.
Symptoms include pain in the bones of the back, the long bones, and the chest. As the
disease progresses, additional symptoms develop. These include fatigue, paleness,
rapid heart rate, shortness of breath, and yellowing of the eyes and skin (jaundice).
People with sickle cell trait are heterozygous for the mutation. They do not have the
symptoms of sickle cell anemia. Another example is the collagen genes mentioned
above. Many bonesdevelop from a cartilage template. This cartilage template is made
out of many proteins, with type II collagen, the predominant protein in the cartilage.
The gene for this collagen, COL2A1, when mutated, not only affects the skeletal system,
but due to its pleiotropic nature, it may also affect a person’s eyes and hearing.

Epistasis
Epistasis is when a gene at one location (locus) alters the phenotypic expression of a
gene at another locus. Epistasis takes place when the action of one gene is modified by
one or several other genes. These genes are sometimes called modifier genes. The gene
whose phenotype is expressed is said to be epistatic, while the phenotype that is altered
is said to be hypostatic. Sometimes hypostatic phenotypes are completely suppressed.
Epistatic genes are not dominant over the genes they alter or suppress. Dominance
refers to an interaction between alleles of the same gene, not different genes.
Examples of epistasis can be seen at both the genomic level and the phenotypic level. At
the genomic level, it is highly possible that under certain conditions one gene could code
for a protein that prevents transcription of the other gene. At the phenotypic level,
examples include the gene causing albinism hiding the gene controlling the color of a
person's hair. In another example, a gene coding for a widow's peak would be hidden by
a gene causing baldness.
Epistasis is also seen in people with red hair. These individuals are homozygous for the
red hair alleles, masking the expression at the brown/blonde hair loci, resulting in red
hair. At least two genes are involved in hair color. One hair color phenotype (brown vs.
blond) has a dominant brown allele and a recessive blond allele. A person with a brown
allele will have brown hair; a person with no brown alleles will be blond. This explains
why two brown-haired parents can produce a blond-haired child. The other gene pair
has a non-red vs. red set of alleles, where the non-red allele is dominant and the allele
for red hair is recessive. A person with two copies of the red-haired allele will have red
hair, but it will be either auburn or bright reddish orange depending on whether the first
gene pair gives brown or blond hair, respectively.

Summary
 Traits controlled by more than two alleles have multiple alleles.
 Many genes have multiple phenotypic effects, a property called pleiotropy.
 Epistasis is when a gene at one location (locus) alters the phenotypic expression
of a gene at another locus.

Review
 Define multiple allele traits.
 Compare and contrast pleiotropy and epistasis. Give examples of each.
 How are collagen genes an exmaple of pleiotropy?