Codominance

More About Blood TypeEarlier 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 H2. Is composed of lipid and 3 terminal sugar residues3. May be modified by enzymes encoded at a second locus

Blood TypeThe 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 galactoseIO does not encode a functional enzyme

Blood TypeHomozygous 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 areare codominantcodominant to each to each other, but dominant to other, but dominant to IIOO. .

Homozygous IO IO individuals exhibit only unmodified substance H.

Blood TypeBoth 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 PhenotypeAn 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 PhenotypeDue 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-SecretersIndividuals 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 antigensA 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 antigensThe 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 AntigensThe 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 RatioEpistasis, incomplete dominance and codominance

are all examples of gene interactions that will result in outcomes of dihybrid crosses differing from the expected Mendelian Ratio.

ModificationsFor example, the codominance of the genotype IA IB

results in the following ratio when heterozygotesare mated:

IA IB x IA IB

Results in ¼ IA IA

2/4 IA IB

¼ IBIB

Or, 1:2:1

EpistasisDevelopment 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.

ComplementationIf 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 F1generations are assessed.

ComplementationThere 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-LinkageGenes that are located on the X chromosome are said

to be XX--linkedlinked. 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 TraitsA 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 TraitsSex-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 MaleBB Bald BaldBb Not bald Baldbb Not bald Not Bald

Genetic BackgroundGenetic 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 InfluencesTemperature 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: TemperatureHeat 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: NutritionIndividuals 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.

ImprintingVariation 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.