Pedigrees and Risk Flashcards
Why use pedigree charts?
Clear simple summary of information
Can spot patterns easily
In clinical context can explain pattern to patient
Calculate risk of passing on disease or being a carrier
Allows informed choice
What does consanguinity cause?
Increases risk of autosomal recessive diseases. The rarer the disease, greater increase in risk.
What 2 diseases develop over age?
HUNTINGTON’S DISEASE
CAG unstable repeat leads to mutated Huntington protein.
No. of repeats variable:
< 27: normal (stable)
27 – 35: intermediate (unstable)
36 – 39: reduced penetrance (unstable)
40+: full penetrance (unstable)
Repeats increase over generations so severity increases. Effects take time.
MEN-1
Mutated MEN-1 gene (tumour suppressor). Affected people have one allele mutated and 2nd allele mutates over time so benign tumour (adenoma so hormone producing) develops. Tumours develop after inactivation of both MEN1 copies at chromosome 11.
What is risk and how is it calculated?
Risk is a calculation of the predicated chance of having disease or being carrier. Work from person with known phenotype to subject. Start from proband. Multiply risks
e.g. for X-linked if mum has ½ risk of being a carrier, child has ½ chance of being affected à ½ x ½ = ¼ chance of being a carrier. Consider phenotype, disease characteristics, family distribution.
What affects risk?
Which side of family disease is on (X-linked, mitochondrial)
Ethnic background
Information you know about the person (phenotype, biological sex etc.)
What is an example of risk calculation being different to simply having a phenotype?
Hereditary haemochromatosis is an example of an autosomal recessive disease. Mutation in human homeostatic iron regulator protein (HFE) causes excess iron absorption and build up, causing tired and fatigue.
1/200 Northern Europeans homozygous but of these only 10% have clinically relevant accumulation of iron i.e. get symptoms (0.05%)
What happens in the presence of sodium dodecyl sulphate?
The speed of migration of proteins on electrophoresis through polyacrylamide gels depends on their size not their charge
What is the role of 2-mercaptoethanol?
2-mercaptoethanol is a sulphydryl reagent which reduces the disulphide bonds between cysteine residues in proteins
What is a convention of genes shown in sequences?
Coding strand shown (one that is same as mRNA except T instead of U) but actually its the other strand which gives rise to precursor mRNA during transcription.
What happens when glycine is replaced by another amino acid?
Larger amino acids in the mutant molecule will cause steric hindrance which generates a kink in the normally straight triple helix, with a resulting defect in the assembly into fibres.
Why is glycine being substituted by cysteine in type 1 collagen chain disruptive?
Cysteine contains a reactive sulphydryl group in its side chain. Thus not only is formation of the collagen triple helix disrupted but there can be inappropriate disulphide bonds between the two α1(I) chains in the helix. The resulting crosslinked polypeptide chains will migrate much more slowly than the individual chains when examined by gel electrophoresis in the presence of SDS. However in the presence of 2-mercaptoethanol the disulphide bonds will be cleaved allowing the chains to migrate according to their molecular weight.
