Pedigrees and Risk

Question 1

Why would you not draw a pedigree for a disease gene?

Answer 1

• many diseases are a mix of familial and sporadic
• many causative gene isn’t known
• impossible to test everyone for disease genes
• when disease exclusively familial and mutation known many do not want to test

Question 2

What are potential difficulties of pedigrees?

Answer 2

Incomplete info (may not have info on all or many relatives)
Incorrect info\Family history may not be correct
Important in clinical setting

Question 3

Why draw a pedigree?

Answer 3

Provides a clear simple summary of information
Able to spot patterns easily
Explain pattern to patient
Identify potential carriers of risk gene
Calculate risk of passing on disease/ being a carrier
Many diseases mix of familial and sporadic

Question 4

What is a pedigree chart?

Answer 4

A diagram which shows the presence or absence of a trait within a family across generations, used to analyse the pattern of inheritance through a family

Question 5

What symbol is used to show a male?

Answer 5

Square

Question 6

What symbol is used to show female?

Answer 6

Circle

Question 7

What is used to show a person who is affected?

Answer 7

Coloured in circle

Question 8

How is the difference between X linked Carrier and Autosomal carrier shown on a pedigree chart?

Answer 8

X linked carrier has a dot in the middle, autosomal has half the shape shaded

Question 9

How is a consanguineous couple shown on a pedigree chart?

Answer 9

Double lines connecting the male and female

Question 10

What is the difference between monozygotic and dizygotic twins?

Answer 10

Monozygotic are identical, dizygotic are not (50% shared)

Question 11

If only females are affected, which type of inheritance is it ilkely to be?

Answer 11

Mitochondrial

Question 12

If only males are affected, which type of inheritance is it likely to be?

Answer 12

Y linked

Question 13

If unaffected parents can have affected children, is the pattern of inheritance for that condition likely to be dominant or recessive?

Answer 13

Recessive

Question 14

If affected parents can have unaffected children, is the pattern of inheritance for that condition likely to be dominant or recessive?

Answer 14

Dominant

Question 15

If the condition is more common in females, which type of inheritance does it tend to be?

Answer 15

X-linked dominant - affected males transmit to all daughters

Question 16

If the condition is more common in males, which type of inheritance is it likely to be?

Answer 16

X-linked recessive - affected females transmits to all sons

Question 17

What is risk?

Answer 17

This is a calculation of the predicated chance of having the disease or being carrier

Question 18

Why is calculating risk useful?

Answer 18

It allows parents to make an informed decision as to whether they want to start a family or not given the risk of certain conditions

Question 19

Describe, in detail, the social and cultural issues related to
stigma and bias that might impact upon their decision when deciding whether or not to start a family

Answer 19

A recognition that the couple might be hesitant to seek medical advice at this
point, due to a sense of shame/stigma surrounding sickle and a desire not to mark
oneself out as ‘different’ or ‘disadvantaged’ (1 mark).
Recognition of the potential unconscious bias of the medical professional when
carrying out a consultation (1 mark).
Mention of the historical roots of such stigma (1 mark).
Students might cite the scientific racism of the 19th century that argued for
quantifiable biological and anatomical differences between the black and white

Question 20

What information do you have to take into account for risk?

Answer 20

Phenotype
Disease characteristics
Family distribution for X-linked and mitochondrial disease
Which side of family disease is on
Which parent has the disease
Ethnic background
Founder effect
biological sex

(All info)

Question 21

What is the Founder effect?

Answer 21

the founder effect is the loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population

Question 22

Which continent is the area with the highest prevalence of sickle cell trait?

Answer 22

Asia

Many diseases have different prevalence in different populations

Question 23

What is hereditary haemochromatosis?

Answer 23

Hereditary (familial) haemochromatosis autosomal recessive disease
Mutation in human homeostatic iron regulator protein (HFE)
Result is excess iron absorption. Humans cannot excrete excess iron so builds up in tissues
Wide range of symptoms including tiredness

Question 24

Give examples of risk modifiers. (3)

Answer 24

Which side of the family the disease is on
- x-linked, mitochondrial

Ethnic background
- different prevalence in different populations
- heterozygote advantage
- founder effect

Information you know about the person
- their phenotype
- biological sex