Risk of Transmission of Disease

Question 1

State the differences between monogenic and complex diseases.

Answer 1

Monogenic diseases are rare, have a clear inheritance pattern and are not affected by environmental factors Complex diseases are the opposite

Question 2

define homologous chromosomes

Answer 2

matching (but non-identical) pair of chromosomes - one from each parent.

Question 3

define mendelian inheritance

Answer 3

The process whereby individuals inherit and transmit to their offspring one out of the two alleles present in homologous chromosomes.

Question 4

define an allele

Answer 4

alternate forms of a gene or DNA sequence at the same chromosome location (locus)

Question 5

name two types of mutation

Answer 5

• point mutation - frame shift mutation

Question 6

State the difference between mutations and polymorphisms.

Answer 6

Mutations are any changes in genetic material that are hereditary Polymorphisms are mutations which occur at >1% frequency in the population

Question 7

State two different types of point mutations

Answer 7

Non-sense - mutation means that the codon codes for a stop codon so the polypeptide chain ends prematurely Mis-sense - mutation means that the codon changes to code for a different amino acid.

Question 8

State two types of frame shift mutations.

Answer 8

Insertion deletion InDel

Question 9

characteristics of autosomal dominant

Answer 9

• at least one affected parent - 50% chance of child affected eg huntingdons

Question 10

Give an example of an autosomal dominant disease and the mechanism of action.

Answer 10

Huntingdon’s Disease – - mutations in the HTT gene on Chr 4, which codes for huntingtin. - Mutation leads to production of a toxic protein that accumulates and forms clumps in organs. - Causes cell death in the basal ganglia in the brain. - It is caused by an unstable CAG repeat – the more repeats you have the more likely you are to get HD. Severity increases with time and age of onset decreases.

Question 11

what are the molecular bases of huntingdons disease?

Answer 11

• Caused by an unstable triplet repeat (CAG) - Number of repeats may EXPAND with each generation - More Repeats = More Likely to be Affected

Question 12

what are patterns of inheritance of huntingdons?

Answer 12

Severity increases with time and age of onset decreases.

Question 13

characteristics of autosomal recessive

Answer 13

• no affected parent - normally no fam history - 25% affected - 50% carrier eg cystic fibrosis

Question 14

Give an example of an autosomal recessive disease and the mechanism of action

Answer 14

Cystic Fibrosis – caused by a mutation in the CFTR gene on Chr 7, CF patients have 2 copies of mutated CFTR gene the absence of functional CFTR affects the chloride ion function which affects chloride ion function in epithelial cells. Gives rise to thick mucus.

Question 15

Give an example of a mutation in the same gene causing two different conditions

Answer 15

Congenital absence of the vas deferens – caused by mutations in CFTR affects 1/2500 men

Question 16

Give an example of a X-linked recessive condition

Answer 16

Haemophilia A and B – A is caused by a mutation in the F8 gene on Chr X which encodes coagulation factor VIII. The affected boys will only receive one copy of F8 B – caused by mutation in F9 gene also on the X chromosome which encodes factor IX the symptoms of both are identical

Question 17

What are the general molecular mechanisms of the different types of genetic disease (autosomal dominant, autosomal recessive, co-dominant)?

Answer 17

Dominant – toxic product produced (treatment aims to neutralise toxic product) Recessive – absence of functional protein (treatment aims to regain function)

Question 18

what are the types of mendelian inheritance patterns?

Answer 18

• autosomal dominant - autosomal recessive - x linked dominant - x linked recessive - mitochondria

Question 19

what are features of X linked recessive disorders?

Answer 19

• no affected parents - usually only males affected - transmitted by the female carrier - sons have 50% chance of being affected - daughters have 50% chance of being the carrier

Question 20

what is the treatment for haemophilia?

Answer 20

• injections with a clotting factor

Question 21

same gene, different mutation, different symptoms

Answer 21

CF and CAVD are both caused by mutations to the CFTR gene

Question 22

same disease, different genes

Answer 22

haemophilia A and B

Question 23

same disease different genes , different inheritance patterns

Answer 23

different forms of epidermolysis bullosa can be autosomal dominant or autosomal recessive.

Question 24

what is incomplete penetrance?

Answer 24

symptoms are not always present in an individual with a disease

Question 25

what is variable expressivity?

Answer 25

disease severity may vary between individuals with the same disease

Question 26

phenocopy?

Answer 26

having the same disease but with a different underlying cause

Question 27

Epistasis

Answer 27

• interactions between disease gene mutations and other modifier genes can affect the phenotype