Lectures 21-25

Question 1

AD: What is neurofibromatosis?

Answer 1

An autosomal dominant condition, skin cafe au lait patches, and this may be accompanied by multiple neurofibroma. It shows variation in expression and is completely penetrant.

Question 2

AD: What is age-dependent penetrance?

What are two examples?

Answer 2

A delay in the onset of a genetic disease

Huntington disease (50% of people with one copy of the altered allele have developed signs by 50)

Breast cancer (80% of women who have inherited BRCA1 allele with a mutation have developed breast cancer by 70)

Question 3

AD: What is the most common form of dwarfism?

Answer 3

Achondroplasia

new mutations cause a disorder in 80% of patients, it is fully penetrant

Question 4

AD: Why would the chance of mutation increase with the age of the father?

Answer 4

the older the male gets, the more cell divisions that sperm has had to go through previously, increasing the chances of mutations

Question 5

What are the effects of anticipation of AD’s?

Answer 5

The phenotype’s age of onset is reduced and the severity is increased in successive generations.

Question 6

What is a key factor for the severity and age of onset for AD’s?

Answer 6

number of repeats

Question 7

AD: What causes Huntington disease?

Answer 7

a triplet repeat of CAG - runs of more han 34 CAG repeats in HD gene expand further, causing earlier age of onset in children of men with HD allele (anticipation)

Question 8

AD: What might happen with gonadal mosaicism?

Answer 8

the production of mutant gametes

Question 9

AR: What is cystic fibrosis?

How is the gene identified?

Answer 9

an Autosomal Recessive disorder
Look for ‘open reading frames’ and search for CpG islands (gene regulatory regions)
A sweat gland cDNA library would then be screened

Question 10

AR: What are the assumptions made for the Hardy-Weinberg principle?
remember, this principle can be applied to AD too

Answer 10

random mating
infinitely large population
no preferential selection of genotypes
no new alleles

Question 11

AR: What are the exceptions to the Hardy-Weinberg principle?

Answer 11

random mating doesn’t always occur!

AR diseases more common in consanguineous matings

Question 12

What is segregation analysis?

Answer 12

the study of how a disorder is inherited.
AD - compare the affected offspring born to affected parents (penetrance)
AR - segregation analysis is more difficult as some carrier parenTs will have no affected children (TRUNCATION)

Question 13

What are the three sources of foetal tissue for prenatal diagnoses

Answer 13

placental tissue
amniocentesis
study foetal cells in maternal blood possibly?

Question 14

How can foetal tissue be studied?

Answer 14

direct muatation analysis (best one)

Genetic linkage analysis, although this requires parental DNA and DNA from a previously affected child

Question 15

What is a key indication of X-linked inheritance?

Answer 15

No male to male transmission

Question 16

What are the key symptoms of Duchenne Muscular Dystrophy?

Answer 16

muscle degeneration
cardiac muscle impairment
intellectual impairment

Question 17

How would Duchenne Muscular Dystrophy be investigated?

Answer 17

serum muscle enzymes (high levels of CREATINE KINASE)
muscle biopsy (absence of staining with ANTIBODIES to DYSTROPHIN)
molecular genetic analysis (identification of deletions/mutations in DYSTROPHIN)

Question 18

X - How does Duchenne Muscular Dystrophy occur?

Answer 18

mutations that alter the reading frame result i the absence of the functional dystrophin protein (65%) of cases?

Question 19

X - What is Becker Muscular Dystrophy?

Answer 19

non frame-shift mutation, which forms a non-functional dystrophin

Question 20

What is X-inactivation?

Answer 20

males and females need the same doses of X - dosage compensation
The process spreads from an X-inactivation centre on Xq
The XIST gene, expressed from the inqactive X, is important in maintaining the silenced state of the rest of the X chromosome

Question 21

Why do some females show X-linked recessive traits?

Answer 21

X-inactivation
skewwed X-inactivation
Turner syndrome (45, X)
homozygous for a recessive trait
X autosome translocations

Question 22

How might X-linked dominant diseases be different to AD’s?

Answer 22

XS of affected females

no male to male transmission`

Question 23

How many genes are in the mitochondrial genome?

Answer 23

37 - most mitochondrial proteins are produced by nuclear genes anyway

Question 24

How are mitochondria inherited?

Answer 24

maternally, as the sperm mitochondria are actively expelled from the fertilised egg

Question 25

What happens if a mutation occurs in the mitochondrial genome?

Answer 25

creates a mixed population of mitochondria within the cell called heteroplasmy, as when cells divide, mitochondria are partitioned at random.

Question 26

AR: how are siblings affected by a single disease?

Answer 26

horizontal transmission

Question 27

AR: What diseases might show a heterozygous advantage?

Answer 27

sickle cell disease, RBC’s sickle at low O2
heterozygotes are malaria resistant
Heterozygotes for CF have a mutant membrane Cl- channel, which stops typhoid infections from entering

Question 28

What happens in a autosomal X chromosome translocation?

Answer 28

The X chromosome involved in the translocation survives preferentially to maintain functional disomy of the autosomal genes