Phenotypic variability

Question 1

Define phenotypic variability

Answer 1

Variation of gene expression in the same disease in different individuals
therefore individuals with the same genetic disease may not present with the same symptoms (phenotypes)

Question 2

What can cause phenotypic variability?

Answer 2

Environment 
Sex 
Modifiers 
Mutation 
Unstable genes

Question 3

How does environment cause phenotypic variability and give and example of this

Answer 3

Where the expression of a gene is modified by environmental factors
In hereditary haemochromatosis (autosomal recessive) there is a mutation in the HFE protein which leads to excess iron absorption - low iron intake improves outcomes

Question 4

How does sex cause phenotypic variability and give and example of this

Answer 4

Gene expression varies by sex either due to the organs/physicality of being that gender or due to X or Y chromosomes

In hereditary haemochromatosis (autosomal recessive) there is a mutation in the HFE protein which leads to excess iron absorption - women lose blood through menstruation therefore have less iron build-up and often do not develop symptoms till after menopause

BRCA1 gene in both men and women - can cause prostrate cancer in men and breast cancer in both

Question 5

How do modifiers cause phenotypic variability and give and example of this

Answer 5

Where expression of a gene is directly affected by presence of another gene

Cystic fibrosis - variety of genes can increase the degree of CF and wildly increase chance if infections
Patients with the same homozygous delF508 mutation can be classified as having either severe or mild lung disease. TGFB1, the gene encoding transforming growth factor beta-1, variants are associated with with the phenotype of severe lung disease.

Both OCA-2 and HERC2 impact eye colour - there are 16 more genes

Question 6

How do unstable genes cause phenotypic variability and give and example of this

Answer 6

Where an increased number of nucleotide repeats (>27) cause more severe phenotypes throughout generations as the repeats accumulate from generation to generation

Huntington’s becomes more severe in future generations
caused by expansion of a region of cytosine-adenine-guanine (CAG)—repeats (i.e. … CAGCAGCAG …), in the Huntington gene.
these repeats results in the production of a chain of glutamine known as a polyglutamine tract or Poly Q tract

Question 7

How do mutated genes cause phenotypic variability and give and example of this

Answer 7

Where different mutated subtypes of the same disease have different presentations

Duchenne v Becker muscular dystrophy are caused by mutations in the dystrophin gene
Diseases are similar in the distribution of muscle wasting and weakness
However Becker muscular dystrophy is a more mild phenotype with age of onset around 12 years as mutation does not result in a frame shift and so active dystophin is produced even though there is less of it
By contrast The mean age at DMD diagnosis was 4.6 years and it is much more severe as DMD the mutation is a frame shift deletion and therefore no active dystrophin is produced.

Question 8

If presentation of a homozygous gene is binary what is the normal explanation for this ?

Question 8

If presentation of a homozygous gene is binary what is the normal explanation for this ?

Question 8

If presentation of a homozygous gene is binary what is the normal explanation for this ?

Answer 8

Modifiers - second gene present

Answer 9

Modifiers - second gene present