Pedigrees and risk Flashcards
What do the following symbols stand for?
How are monozygotic (identical) twins shown on a pedigree?
How are dizygotic (non-identical) twins shown on a pedigree?
How are consanguineous couples shown on a pedigree?
What is a consanguineous couple?
Descend from the same ancestor
How are different generations presented on a pedigree?
Denoted by roman numerals
Oldest generation will be I
How much DNA do siblings share?
50%
25% for half-siblings
How much DNA does an individual share with their grandparents, aunts and uncles?
25%
How much DNA does an individual share with their 1st degree cousin?
12.5%
What are benefits of drawing a pedigree?
Able to spot patterns early
Explain pattern to patient
Identify potential carriers of risk gene
Calculate risk of passing on disease or being carrier
Allow informed choice
Why would you not test for a disease?
Many diseases are a mix of familial and sporadic factors
Many causative genes are unknown
Its impossible to test everyone for diseases
When a disease is familial and the mutation is known many don’t want the test
When are symptoms for huntingtons disease and when is the onset?
30- 50 years
Symptoms: difficulty concentrating, depression, stumbling, involuntary jerking, problems swallowing
What causes huntington’s disease?
Mutation: results from a DNA expansion of a CAG repeat on chromosome 4 causing production of polyglutamine tract (polyQ tract) - autosomal dominant
Abnormal intracellular huntington protein aggregate gains a pathologival function and is toxic to neurones resulting in cell death
What are potential difficulties with a pedigree diagram?
Incomplete information- may not have information on all relatives
Incorrect information
Family history may not be correct
What inheretance pattern is this?
Autosomal dominant
Males and females affected
Vertical transmission
Not all offspring affected
At least 1 affected parent- can be mother or father
50% risk of inheretance
What are complicating factors when investigating patterns of dominant forms of disease?
Age of onset- some diseases develop with age due to accumulation of damage
What pattern of inheritance is this?
X- linked recessive
Only males affected
Not all generations affected
Not all offspring affected
Inherited from unaffected mother (carrier)
If mother is carrier: 50% risk of disease
Any daughters of affected father will be carriers
What pattern of inheritance is this?
Mitochondrial
Vertical transmission
All offspring affected (if affected mother)
Males and females affected
Mitochondria inhereted from mother so inhereted from affected mother
What pattern of inheritance is this?
Impossible to tell
No family history
Could be genetic or non-genetic
Could be a new dominant mutation but could be recessive
What pattern of inheritance is this?
Autosomal recessive
Usually no family history of disease
Parents unaffected
Horizontal transmission
Not all offspring affected
Males and females affected
Obligate carriers
What does risk mean?
This is a calculation of predicted chance of having a disease or being a carrier
How do you calculate risk?
To calculate we work from the person with known phenotype to subject
Multiply the risks together
What information needs to be taken into account when calculating risk?
Phenotype
Disease characteristics
If X-linked or mitochondrial: what side of family disease is on and which parent has disease
Ethnic background: diseases have different prevalence in different popultions
Calculate the risk
Maternal grandmother (red) must be a carrier: 1/1 chace of being carrier
Mother (blue) must hve a 1/2 chance of being carrier
So her daughter (ther proband) has a 1/2 chance of inheriting the gene
Therefore risk is: 1 x 1/2 x 1/2 = 1/4 risk she’s a carrier
If’s she’s a carrier then theres a 1/2 chance of passing gene onto son
However only 1/2 chance of child being male
So risk of affected son is 1/4 x 1/2 x 1/2
Calculate the risk
Chances are the population risk
Paternal grandmother is a carrier
Father is not affected so mutation not passed to daughter
Calculate the risk
Risk is the population risk
Autosomal dominant- neither parents affected
Relatives likely to have sporadic form
Calculate the risk
Mother affected therefor 1 in 2 chance he has inherited the gene
Calculate the risk
Chance that Mr T is carrier is 1/2 x 1/2 x 1/2 = 1/8
Chance child being affected if both parents are carriers is 1/4
Population chance is 1/22
So chance child will have CF is 1/8 x 1/4 x 1/22
What is hereditary haemochromatosis?
Autosomal recessive
Cuased by mutation in human haemostatic iron regulator protein
Results in excess iron absorption. Humans can’t excrete iron so it builds up in tissues
Wide range of symptoms including fatigue
Chronic tiredness fatigue one of main symptoms in primary care patients
