Advanced Mendelian Genetics Flashcards
What is an allele
Are different variants of the same gene
They correspond to the same region of DNA (same locus) but have some differences in base sequences
What is a dominat allele
Produces an effect on the phenotype when present in either one or two copies
What is a recessive allele
A recessive allele produces an effect only when there is no dominat allele present
What is a ‘wild-type’ of an enzyme
The allele that encodes for the normal working copy og the enzyme which is usually domiant
non-functional enzyme which code for mutant alleles are usually
recessive
In the vast majority of cases, how could an individual synthesize the mutant but the reaction can proceed as normal
In most cases having half the normal amount from one working copy of the gene is enough to allow the reaction to proceed as normal
In the same way, if there was only one gene ‘wild-type’ which coded for the functional enzyme and one gene which produced a non-functional enzyme - what would this combination of allele be called
Heterozygous
What is Haplosufficient
Having half the usual amount of the catalyst present is enough for the reaction to proceed
A mutation that results in a non-working version of a protein is usually recessive
BUT not aways and this is called…
This is called a Dominat Mutant allele
What is Haploinsufficiency
The presence of half the normal amount of a protein (from one functional allele) is not enough to give the normal phenotype
With Haploinsufficiency, a heterozygous genotype with one wild type and one mutant allele results in
Half the normal amount of protein codes
And the mutant phenotype
Heterozygotes are
Phenotypically normal but are carriers of disease - autosomal recessive disorders
What can Haploinsufficiency lead to
An intermediate phenotype ‘incomplete dominance’
For the vast majority of cases an individual will be
Haplosufficient
What is a dominat negative allele, and how do they work?
- Result from mutation that prevent the action of a protein and cause the mutant protein to inhibit the action of non-mutant molecules of the same protein inside cells
- So proteins product does not work but also prevents other normal products of the same protein from working properly
When are dominat negative alleles often seen
When a protein works as a dimer or part of a larger complex
What is gene interaction
Occurs when a new phenotype is produced dependent on the action of alleles of several genes
e.g. the fruit colours in peppers
Results in the 9:3:3:1 interaction saw in the F2 generation
How does the fruit colour come about through the interaction of two genes in peppers
R and C genes
Yellow pigment is converted to red pigment if there is at least one copy of the dominant R gene
Dominant C gene prevents the build up of chlorophyl in the skin of the pepper
RC - red, rrC - yellow, Rcc - brown, rc - green
BUT other colours like orange, pale yellow and white can occur in peppers, how?
Recessive alleles of two further genes can reduce the amount of red or yellow pigment
Two recessive alleles of one of these genes can make a RC (red) phenotype appear orange and a rrC (yellow phenotype) look pale yellow
Two recessive alleles of both of these genes can make a rrC (yellow phenotype) look very pale yellow/white
What is Epistasis
- Depends on interactions between genes
- E.g. The effect of one gene is ‘hidden’ by the effect of a gene at a different locus
- The ‘hidden’ gene is hypostatic to the other gene, whic is epistatic
What is Epistasis
- Depends on interactions between genes
- E.g. The effect of one gene is ‘hidden’ by the effect of a gene at a different locus
- The ‘hidden’ gene is hypostatic to the other gene, whic is epistatic
What different genes exist in mice to code for the colour of their hair
- A (agouti gene) - results in yellow bands on dark hair
- Ay (agouti gene) - in the heterozygous form results in yellow hair
- aaB (black/brown gene) - determines background colour of hairs, in this case black
- aabb - results in brown hair
- Abb - result in cinnamon hair
How does epistasis occur in mice hair colour
a C gene (epistatic over A and B) - determines pigment production
CC/Cc - results in full colour production
cc - results in albino mice
There are also other gene which affect mouse coat phenotype
These can include:
Curly vs Normal
Full colour vs faded
Spots vs no spots
These are known as modifer genes - they do not hide the effect of the colour genes BUT they do modify the phenotype which is produced
What does Epistasis primarily effect within a cell
Epistatic interactions can occur when the genes involved encode enzymes in the same biochemical pathways
E.g. flower colour in sweet peas
How is Epistasis occuring in the flower colour in sweet peas
The C gene is Epistatic over the P gene because in the presence of two recessice c alleles the effect of the P gene is hidden
Conversely the P is hypostatic to the C
What is Penetrace
The probability that an individual with an appropriate genetype will show a change in the phenotype
May be complete (100%) or incomplete (<100%)
What is expressivity
The degree of phenotypic change produced by a genotype, can be variable (not necessarily all or nothing)
What are the issues with penetration and expressivity in genetic analysis
It makes it very hard to determine which individuals have inherited a mutant allele and which haven’t
Given an example of a disease which varies in penetration and expression
Huntington’s disease - autosomal dominant
Variable expressivitiy and incomplete penetrance
Has a variable age of onset - due to the variable expressivity
Incomplete penetrance - means not all individuals develop the phenotype during their lifetime
The incomplete penetrance is due to variable expressivity
How does huntingtons relate to trinucleotide repeats
Trinucleotide repeat expansion causes disease (this is the mutation)
Individuals with more copies than usual have a mutant version of the gene
Number of repeat linked to the expressivity - individuals with lots more copies than usual tend to have earlier onset diease
What is the difference between normal huntingtons and mutant huntingtons
- Normal huntingtons is involved in nerve cell development and function, it interacts with many other proteins involved in processes including endocytosis, apoptosis, cell signalling, transcription etc
- Mutant huntingtin is misfolded, accumulates in nerve cells and has a toxic effect
What is the main cause of variable expressivity
More usually variable expressivity depends on the genetic background of different individuals i.e. other genes in the background influence the phenotype produced by the genes of interest
Interactions with modifer genes
What is a genome map
Show the position of the genes on the chromosome
There are two ways to map the genome, what are they?
- Gentic maps - based on recombination and linkage
- Physical maps - completed DNA sequence of a genome with positions of genes mapped
How does Genetic mapping work
- Based on mapping genes relative to each other or another feature of the genome (marker)
- Produced by oberving the outcome of crosses
- The amount of recombination in the DNA that seperates two genes is measured and covered into map units
What is genetic linkage
Alleles of genes that are close together on the same chromosome tend to be passed on together to offspring
What affects genetic linkage
Recombination opposes linkage
When chromosome pair during meiosis (to form gametes) pieces of DNA get swapped between them which mixes ip the combination of alleles
The amount of recombination depend on
If recombination is equally likely to occur at any position along the chromosome, there is more likely to be a recombination event in the DNA between genes far apart than genes closer together
