The susceptibility of developing the tumour is a dominant trait, but 20 per cent of individuals who have the altered allele do not develop the condition. The retinoblastoma gene therefore has an 80 per cent penetrance.
CLASSIFICATION OF GENE ACTION
Dominance usually occurs when a functioning allele is paired with a non-functioning allele. This usually arises from a mutation that alters the DNA structure within the allele, rendering it non-functional. An individual who has two altered alleles will generally display a distinctive phenotype as a result of the missing or altered protein produced by the altered alleles. It is not the lack of function that makes the allele recessive but the interaction of that allele with the alternative allele in the heterozygote. There are three main allelic interactions.
1. Haplosufficiency
This is when a single functional allele is able to encode for a sufficient amount of protein in order to produce a phenotype that is identical to that of the normal phenotype. If each allele encodes for 50 per cent of the amount of protein (100 per cent from both functioning alleles) and the normal phenotype can be achieved with only 50 per cent of the protein, then the functioning allele is considered dominant over the non-functioning allele. For example, the GALT gene on chromosome 9p that normally encodes for an enzyme needed for the breakdown of galactose shows haplosufficiency in the presence of one altered gene.
2. Haploinsufficiency
This is where a single functioning allele is unable to produce enough protein. Essential levels of protein must be over 50 per cent in cases of haploinsufficiency. The phenotype in haploinsufficiency resembles the homozygote for the non-functioning allele. This is rare in humans as deficiency usually results in a case of incomplete dominance.
3. Incomplete dominance
With a small number of alleles there is a lack of complete dominance. A heterozygous individual will have an intermediate phenotype compared with the two different homozygous individuals. The phenotype of the heterozygote becomes an intermediate or a ‘blend’ of the two different alleles. A simple example of incomplete dominance in humans can be seen with the gene for curly hair. An individual who has inherited a curly hair allele from one parent and a straight hair allele from the other parent will have wavy hair. In humans the ‘blend’ of the curly hair allele and the straight hair allele gives rise to wavy hair.
Most genes that display patterns of incomplete dominance have arisen from alleles in which a ‘loss of function’ has occurred. In a gene composed of one functioning allele and a non-functioning allele, only half the required amount of protein is encoded for by that gene. The genetic condition of familial hypercholesterolaemia demonstrates incomplete dominance in that individuals with one faulty or non-functioning allele will have raised blood cholesterol levels, while individuals who have two non-functioning alleles will have much higher cholesterol levels.
| ACTIVITY 3.3 |
The straight hair allele (s) and the curly hair allele (c) show incomplete dominance in humans. Individuals with straight hair are homozygotes (ss), as are individuals who have curly hair (cc). Heterozygotes for this trait have wavy hair as they have one straight hair allele and one curly hair allele (sc). Note that the two different traits are represented by different letters.
a. Complete a Punnet square for a mating between a curly hair individual and a wavy hair individual.
b. What is the predicted offspring from this mating?
c. Is it possible for these individuals to have a straight hair child with each other?
d. Complete a Punnet square to determine the possible genotypes of the offspring of two wavy hair individuals.
e. Could two wavy hair parents have a child with straight hair?
f. Could the same wavy hair parents have a child with curly hair?
Whether an allele is classified as dominant or incomplete dominant depends on the individual’s phenotype. However, the phenotype can be measured in different ways. Take, for example, the genetic condition of Tay–Sachs disease. Tay–Sachs disease is a degenerative condition that affects the nervous system. Affected individuals are born healthy but start to lose acquired skills at around the age of six months, gradually becoming blind, paralysed and unaware of their surroundings. It is a lethal condition with an average life expectancy of around five years. Affected individuals have two altered alleles in the HEXA gene on chromosome 15. A functioning HEXA gene is vital for development of the nervous system. Without the specific enzyme that this gene encodes for, fatty deposits build up in the brain, which then leads to neuronal damage. An affected individual has two non-functioning HEXA alleles. A heterozygote individual who has one functioning copy of the gene will be able to produce half the normal amount of the HEXA protein, which is enough to prevent damage from occurring. Heterozygotes are therefore carriers of Tay–Sachs disease. The healthy functioning copy of the HEXA allele is therefore classified as dominant to the non-functioning HEXA allele as the heterozygote individual displays no symptoms of the condition. However, if enzyme levels were measured, only half the usual amount of the HEXA enzyme protein would be discovered. In Tay–Sachs disease half the enzymatic levels are sufficient for health. At the biochemical level, the heterozygous individual displays incomplete dominance but complete dominance at the whole body level.
All the examples so far have demonstrated one allele being dominant or recessive over its partner allele. There are some conditions in which different versions of the same allele demonstrate equal dominance to each other. This is called co-dominance.
CO-DOMINANCE
Co-dominance is quite similar to incomplete dominance, in that neither of the two alleles is dominant or recessive to each other. However, there is no ‘blending’ in the offspring as both allelic products are expressed. Both parental traits are expressed in the offspring with co-dominant alleles. The biggest difference between incomplete dominance and co-dominance is that in co-dominance both alleles still encode for a functioning protein. The different proteins may have a slightly different function.
Most co-dominant alleles are thought to have arisen from a ‘gain in function’ mutation, where the alteration to the DNA structure within the allele has resulted in a different functioning protein being encoded for.
The MN blood group
An example of a co-dominant gene in humans is the gene that encodes for the MN blood group. The MN system is a type of blood grouping that is formed by the presence of specific antigens on the surface of the red blood cells. Two co-dominant alleles were originally identified for this blood group, termed M and N. The MN system is under the control of the MN gene located on chromosome 4. As both M and N alleles are co-dominant to each other there are three possible genotypes and phenotypes that can arise from the MN blood grouping system (see Table 3.4).
Tale 3.4 The MN blood grouping system
| Genotype | Phenotype |
| MM | MM blood group |
| NN | NN blood group |
| MN | MN blood group |
There is distinct expression of both alleles in the MN blood group system, which is a characteristic of co-dominant inheritance.
| ACTIVITY 3.4 |
In
