Codominance

More About Blood Type

Earlier in the semester, we discussed Substance HSubstance 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 N-acetylegalactosamine.

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 TypeHeterozygous 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, Therefore, IIAA and and IIBB are codominant to each are codominant to each other, but dominant to other, but dominant to IIOO. .

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 analysiscomplementation 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-linkedX-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

Phenotype

Genotype Female Male

BB Bald Bald

Bb Not bald Bald

bb Not bald Not Bald

Genetic Background

Genetic backgroundGenetic 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 positionposition 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 amphibiansCoat 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 sensitivetemperature 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.