Lecture 15: Variations on Dominance Flashcards
Explain Mendel’s Second law: 4
- “Law of dominance: one form of a gene masks the other (one allele is dominant, the other recessive)”
2, This is where our familiar 3:1 ratio comes from.
- The heterozygote possesses two alleles that affect a trait, but only one is displayed (the dominant one). Hence a heterozygote has the same phenotype as the homozygotes.
- But we all know life is not that simple:
Some traits, especially non-discrete characteristics (e.g. height) do not fit Mendel’s simple laws of inheritance.
What is incomplete dominance/ partial dominance?
a form of Gene interaction in which both alleles of a gene at a locus are partially expressed, often resulting in an intermediate or different phenotype.
The genotypic and phenotypic ratios are the same! This is because each genotype has its own phenotype
AFTER LOTS OF Experimenation WHAT TWO CONCLUSIONS ON DOMINANCE WAS MADE?
- Dominance affects the phenotypes that genes produce, but NOT how genes are inherited.
- Dominance is established by observing the phenotype of heterozygous individuals.
Explaining Co-dominance; example?
- the heterozygous phenotype is NOT intermediate between that of the two homozygotes. Instead, the heterozygote expresses the phenotypes of BOTH homozygotes simultaneously.
Key example: ABO blood grouping
- Three major alleles i, IA, IB, which determine the presence of sugar molecules on the surface of red blood cells. These sugars act as antigens. Blood group incompatibility arises because adults produce antibodies opposite to their own antigen (e.g. blood group A makes anti-B antibodies).
- IA and IB produce different sugars (blood groups A and B), whereas i gives none (blood group O).
- An individual has two alleles that together give the four blood groups (phenotypes) from six different genotypes.
- IA and IB are co-dominant over i because both A and B antigens are expressed simultaneously
DEFINITIONS: COMPLETE DOMINANCE, INCOMPLETE DOMINANCE, CODOMINANCE
COMPLETE DOMINANCE: Phenotype of the heterozygote is the same as the phenotype of one of the homozygotes.
INCOMPLETE DOMINANCE: Phenotype of the heterozygote is intermediate (falls within the range) between the phenotypes of the two homozygotes.
CODOMINANCE: Phenotype of the heterozygote includes the phenotypes of both homozygotes.
Dominance depends on the level of the observed phenotype: SICKLE CELL ANAEMIA = what is it, how it affects, the genetics (7)
- Sickle cell anaemia results from a mutation in the haemoglobin (Hb) gene (Chr 11)
- Most common mutant allele encodes single amino acid substitution in the β-globin gene, causing haemoglobin molecules to aggregate under low oxygen concentrations.
- Red blood cells deform and flow poorly in capillaries. Such cells are broken down.
- Anaemia results from decreased numbers of functional blood cells to carry oxygen.
- WT Hb allele = HbA, mutant Hb allele = HbS
- Sickle cell heterozygotes (“sickle cell trait”) express both forms of haemoglobin, A and S
- Due to different amino acid sequences, they migrate differently on a protein gel and can be identified
The key genotype is the heterozygote because:
At level of anaemia, HbA allele is dominant…
At level of blood cell shape, HbA is incompletely dominant… At level of haemoglobin, HbA and HbS are co-dominant!
Back to Cuénot’s mice..Why is this relevant to the concept of dominance?
Most lethal alleles are recessive: complete loss of an essential gene.
Dominant lethality should be impossible because both homozygotes and hets would die.
Is it possible to have a dominant lethal allele?
What makes an allele recessive or dominant?
Recessive mutant alleles vs Dominant mutant alleles.
1 * Remember: a mutant phenotype is defined by the normal or “wild type” (WT) phenotype
2 * Recessive mutant alleles normally result from loss of function or reduced function mutations e.g. premature stop codon leads to incomplete protein
3 * The WT counterpart of a loss-of-function allele is therefore the dominant allele
4 * Dominant mutant alleles often result from a gain of function mutations e.g. a mutation that leads to ectopic expression of the protein (wrong time or place), or a protein that interferes with the function of normal protein
5 * The WT counterpart of a gain-of-function allele is therefore the recessive allele
Explain Loss-of-function recessive alleles
When a heterozygote consists of the wild-type allele and the loss-of-function allele, the level of expression of the wild-type allele is often sufficient to produce the wild-type phenotype.
Loss-of-function recessive alleles
* Mendel’s peas: hypothesis, What is the causative mutation for the green phenotype
- Mendel’s peas: yellow (Y) is dominant to green (y): Yy is yellow
- Pea seeds are green when immature, and normally turn yellow when mature and dry
- Therefore Yellow is wild type and Green is mutant
HYPOTHESIS: The y allele is a loss-of-function recessive mutation because green seeds
lack something required to turn them yellow.
What is the causative mutation for the green phenotype?
The yy green phenotype results from mutations that affect the expression of a gene
called STAYGREEN (SGR).
SGR encodes an enzyme that breaks down chlorophyll (Chl). Some y alleles result from mutations that lead to amino acid substitutions or insertions in the SGR enzyme, so becoming non-functional.
Chl not degraded -> seeds stay green.
Explain: Gain of function dominant alleles
mutations that result in elevated levels of gene activity.
Any heterozygote containing the new allele along with the original wild-type allele will express the new allele
Gain-of-function dominant alleles: (3) Antennapedia (Antp)
- Antennapedia (Antp) encodes a homeobox transcription factor that specifies segment identity (leg development)
- In dominant Antp mutants, gene is ectopically expressed in head region of embryo – the “gain of function” – and legs form in place of antennae.
- Mutation in control of Antp expression.
Other reasons for the dominance:
Haploinsufficiency
Dominant negative
- Haploinsufficiency: this is a special case of loss-of-function – one functional gene is not enough.
NOTE: here, a loss-of- function allele is dominant! - Recessive alleles are almost always loss-of-function alleles, but the reverse is not always true (e.g. haploinsufficiency).
- Dominant negative: a mutant protein disrupts the function of the normal protein
Characteristics of dominance: 3
- Dominance is allelic interaction: a result of interactions between DNA variants at the same locus.
- In turn, allelic dominance comes about through the gene products interacting with each other.
- Classification of dominance depends on the level at which the phenotype is examined.
New concepts: Penetrance and Expressivity:
COMPLETELY PENETRANT
INCOMPLETE PENETRANCE
- Many traits show complete correspondence between genotype and phenotype e.g. ABO blood groups. Given the genotype, we can predict the phenotype with 100% accuracy. The phenotype is said to be ***completely penetrant.
- Sometimes, there is not a perfect correspondence between genotype and phenotype – individuals with the same genotype may have different phenotypes: incomplete penetrance.
Example: polydactyly…
Many traits show complete correspondence between genotype and phenotype e.g. ABO blood groups. Given the genotype, we can predict the phenotype with 100% accuracy. The phenotype is said to be ***completely penetrant.
Sometimes, there is not a perfect correspondence between genotype and phenotype – individuals with the same genotype may have different phenotypes: ***incomplete penetrance.
