IMEG Flashcards
Autosomal dominant inheritance characteristics
- at least one affected parent
- no skipping of generations
- males and females equally likely to be affected
- transmitted by either sex
Examples of autosomal dominant disorders
- achondroplasia, mutations in FGFR3
- Marfan syndrome - which is a connective tissue disorder, mutations in FBN1
- Huntingdon’s disease is a progressive neurological disease, increased length of CAG triplet repeat
Autosomal recessive characterisitics
- both males and females affected
- if both parents affected, children usually will be
- usually affected children will have parents who are carriers but not affected
- affected individuals with normal partners usually have normal children
- both copies of gene have to be mutated for phenotype to be abnormal
Autosomal recessive example and what it affects
cystic fibrosis
affects the lungs, pancreas, sweat glands and sometimes other organs
What is the mutation in cystic fibrosis and what does it do?
CF gene is on chromosome 7 which encodes a transmembrane protein that transports chloride ions. The mutation disrupts normal chloride transport.
Treatment for cystic fibrosis
- intake of digestive enzymes
- postural drainage or lungs
- inhalation of medicines
- gene therapy
X-linked recessive inheritance characteristics
- mainly males affected
- affected males are born to unaffected parents
- no male to male transmission
- only one mutant allele required on the X chromosome
X-linked dominant inheritance characteristics
- either sex affected
- usually at least one affected parent
- for an affected male, all daughters but no sons will be affected
Y-linked inheritance
- only males affected
- affected males always have affected father
- all sons of affected father are affected
What is translocation?
A segment of DNA on one chromosome breaks and moves onto another chromosome. This forms a larger abnormal chromosome. There are still 46 chromosomes. Usually, part of chromosome 21 moves onto chromosome 14
What are satellite regions?
bits of DNA that stick up above the chromosome
What is a hydatidiform mole?
When all chromosomes are of paternal origin
Give 2 example of a loss of function mutations
a-thalassaemia - deletion of a-globin gene
ATM - ataxia telangiectasia mutated
Give 2 examples of gain of function mutations
FGFR3 mutation in achondroplasia
Down syndrome - increases production of normal protein
What happens in the FGFR3 mutation?
causes independent activation of the tyrosine kinase domain
causes innapropriate inhibition of chondrocyte proliferation
leads to shortening of bones - achondroplasia
What is the mutation in sickle cell anaemia?
Single base change that changes the amino acid from glutamine to valine
It decreases the solubility of deoxygenated Hb
forms stiff fibrous polymers that distort RBC giving it a sickle shape
What is a multigenic trait and give two examples
multiple genes involved
digenic disorder
retinitis pigmentosum
What is ataxia tenlangiectasia?
Autosomal recessive disorder
progressive cerebellar degeneration
immunodeficinecy
unusual sensitivity to ionising radiation
It is a recessive disorder so individuals are either homozygous for the ATM mutation of heterozygous with two different mutations
How could you test for AT?
X-ray induced chromosome damage due to exposure to radiation - AT patients are extra sensitive to ionising radiation
Increased radiation sensitivity means there will be increased DNA double strand breaks
Would a carrier of the ATM gene be expected to show heightened sensitivity to radiation?
No
What can be used to detect the ATM protein and what will it tell you?
Western blot
Will show the presence/absense of protein but won’t give an indication of how ,much protein is present
Even if protein is present, Western blot will not give information about whether it is functional
What does an absense of the ATM protein show?
It is a feature of AT caused by a nonsense mutation
What could the presence of the ATM protein show?
- patient doesn’t have AT
- patient could have AT but the protein has been mutated by a missense mutation - protein will be present but not functioning properly
Analysis in patients with no ATM function
expectation would be to find two null mutations
Two nonsense mutations leading to truncated proteins leads to total loss of protein
