Codominance
More About Blood Type
Earlier in the semester, we discussed Substance H, which
forms the basis of blood type.
Substance H is
1.
Encoded at the H locus; H encodes the normal
substance, h encodes an incomplete substance H
2.
Is composed of lipid and 3 terminal sugar residues
3.
May be modified by enzymes encoded at a second locus
Blood Type
The enzymes that modify substance H are encoded
by genes at the I (isoagglutinogen) locus. There are
three alleles for this locus:
IA encodes an enzyme that adds a terminal Nacetylegalactosamine.
IB encodes an enzyme that adds a terminal galactose
IO does not encode a functional enzyme
Blood Type
Homozygous
IA IA exhibit the N-acetylegalactosamine modification
on their blood cells.
IB IB exhibit the galactose modification on their blood
cells.
Blood Type
Heterozygous IA IB exhibit both modifications on the
surface of their blood cells.
Heterozygous IO IA or IO IB are phenotypically
identical to homozygous IA IA or IB IB.
Therefore, IA and IB are codominant to each
other, but dominant to IO.
Homozygous IO IO individuals exhibit only
unmodified substance H.
Blood Type
Both the A and B antigens elicit an immune response
when encountered by immune systems unfamiliar
with the substances, i.e., a person with only the B
antigen will mount an immune response when
blood cells exhibiting the B antigen are transfused,
and vice versa.
The O antigen is not immungenic; therefore type O
blood can be infused to people exhibiting A, B or
O antigens without problems.
The Bombay Phenotype
An unusual mutation in substance H was first
identified in 1952.
Found to lack either A or B antigens, a woman in
need of a blood transfusion was classed as blood
type O.
However, one of her parents was type AB, her
husband was type A, but two of her offspring
exhibited the IB allele (one type AB, one type B)
The Bombay Phenotype
Due to homozygous inheritance of a rare mutation h,
she exhibited a form of substance H that could not
be terminally modified.
She was genetically type B, but functionally type O
(phenotypically type O).
More about blood types—Secreters
and Non-Secreters
A third locus affects expression of the A and B antigens,
called the Se locus.
The dominant allele, Se, causes the A and B antigens to be
secreted in body fluids such as semen, saliva and vaginal
fluids. About 80% of the human population are either
Se/Se or Se/se and produce the antigens in body fluids.
Individuals homozygous for the recessive allele, se, make
the antigens but do not secrete them in body fluids and
are called “non-secreters.”
Secreters and Non-Secreters
Individuals homozygous for the recessive allele, se,
make the antigens but do not secrete them in body
fluids and are called “non-secreters.”
Prior to the development of DNA identification
analysis, secreter status was a key forensic tool.
More about blood types—Rh antigens
A fourth locus and another example of multiple
alleles contributing to blood type are the Rh
antigens.
They were discovered because of their involvement
in the disorder erythroblastosis fetalis, which until
recently, was usually fatal in affected fetuses.
Rh antigens
The problem arises when an Rh- woman gives birth
to an Rh+ baby.
During parturition, the mother is exposed to the
foreign blood cells, and unless treated, will mount
an immune response. (Think of her as being
“vaccinated” against the fetal blood type)
Rh Antigens
The first pregnancy will be normal, but if she becomes
pregnant with another Rh+ baby, her body will mount a
vigorous immune response.
During the course of the pregnancy, some of the maternal
blood cells enter the fetal circulation and begin to destroy
fetal blood cells and result in hemolytic anemia.
Doctors now treat Rh- women who give birth to Rh+ babies
with anti-Rh antibodies, which circumvents the maternal
immune response by destroying the Rh+ cells that have
entered the maternal circulation.
Modifications of the 9:3:3:1 Ratio
Epistasis, incomplete dominance and codominance
are all examples of gene interactions that will
result in outcomes of dihybrid crosses differing
from the expected Mendelian Ratio.
Modifications
For example, the codominance of the genotype IA IB
results in the following ratio when heterozygotes
are mated:
IA IB x IA IB
Results in ¼ IA IA
2/4 IA IB
¼ IBIB
Or, 1:2:1
Epistasis
Development of pigment patterns in mice is an
example of epistasis.
The gray color pattern in horses is another example
of epistasis. In this case, the gray gene is dominant,
so if a horse inherits the gray gene, it will be gray
regardless of genes present at the primary color
locus.
Complementation
If two different research groups describe mutations
that cause the same phenotype, it is possible to
determine if the groups are describing mutations in
a single gene, or two different genes with
complementation analysis.
The two mutant strains are crossed, and the F1
generations are assessed.
Complementation
There are two possible outcomes:
1. All offspring develop normally. The two
mutations are in different genes and are not
alleles of the same gene. The two mutations
complement each other.
2. All offspring exhibit the mutation. The two
mutations occur in the same gene and are either
the same mutation or are alleles of the gene.
X-Linkage
Genes that are located on the X chromosome are said
to be X-linked.
The Y chromosome contains some homology with
the X chromosome, but lacks most genes present
on the X chromosome.
As a result, genes on the X-chromosome exhibit
some unique patterns of inheritance; e.g. color in
calico cats, hemophilia and muscular dystrophy.
Sex-Limiting and Sex-Influenced
Traits
The individual’s gender influences the phenotype.
These traits are determined by genes on autosomal
chromosomes, but are influenced by the hormonal
environment in the individual.
Sex-limited traits are expressed in only one gender or
the other.
Sex-Limited Traits
A great example of sex-limited traits are those
responsible for milk yield in dairy cattle.
Regardless of the genes that influence milk
production, they are obviously only expressed in
females.
Sex-Influenced Traits
Sex-influenced traits demonstrate different
phenotypes based on gender.
For example, consider male-pattern baldness in
humans, in which the phenotype of the
heterozygous condition is influenced by gender.
Male-Pattern Baldness
Genotype
BB
Bb
bb
Phenotype
Female
Male
Bald
Bald
Not bald Bald
Not bald Not Bald
Genetic Background
Genetic background refers to the principle that
genes are expressed in the context of all the genes
expressed in the genome.
For example, suppressor mutations restore the
phenotype in individuals with a mutation at a
different location. (One mutation suppresses
another.)
Additionally, gene expression may be influenced by
its position in the genome; i.e. a gene that is
expressed if it is in one location may be suppressed
if it is moved to a different location.
Environmental Influences
Temperature can be a potent regulator of gene
expression in certain genes. Some examples:
Sex determination in some reptiles and amphibians
Coat color in Siamese and Himalayan cats– dark
pigment forms in areas of the body where
temperature is slightly lower: tips of ears,
extremities.
These are temperature sensitive genes.
Environment: Temperature
Heat shock proteins are another example of genes
regulated by temperature.
Heat shock proteins are expressed at all
temperatures, but many of them exhibit greatly
increased expression at high temperatures. These
proteins protect cells from the effects of high
temperatures.
Environment: Nutrition
Individuals may exhibit mutations that result in an
inability to tolerate certain nutrients.
Phenylketonuria—cannot metabolize the amino acid
phenylalanine.
Galactosemia—cannot metabolize galactose.
Lactose intolerance—lack the enzyme lactase, which
breaks down lactose, or milk sugar.
Imprinting
Variation in phenotype depending on the parental
origin of the chromosome carrying a particular
gene.
Some regions and the genes encoded maintain some
kind of parental “memory” or imprint, that
influences whether specific genes are expressed or
remain silent. This process is thought to occur
during gamete formation.