Genetics

Question 1

Cystic fibrosis

Answer 1

CFTR on chromosome 7 - regulates passage of Cl- across membranes. 
Mucus becomes thickened= symptoms
Delta 508- class 2 mutation

Question 2

PKU (Phenylketonuria)

Answer 2

Autosomal recessive
Mutations in PAH - phenylalanine hydroxylase
Responsible for metabolising phenylalanine to tyrosine
Causes severe learning disabilities
Single gene multifactorial disorder
Compound heterozygotes- can still be affected but not as serious as homozygotes

Question 3

What is genomic imprinting?

Answer 3

Epigenetic modification of the genome in which some genes in the allele from one of the parents are “closed” down (methylated)
Different features dependent on whether allele is expressed from mother or father

Question 4

Give 2 examples of genetic imprinting disorders.

Answer 4

Angelman- laughing- paternally silenced

Prader-willi - cant stop eating- maternally silenced

Question 5

What are the features of Prader-Willi syndrome?

Answer 5

mental retardation
Hypotonia
gross obesity (diabetes)
male hypogenitalism

Question 6

What are the features of Angelman syndrome?

Answer 6

Mental retardation
Lack of speech
Growth retardation
Hyperactivity
Inappropriate laughter

Question 7

What is variable expression?

Give one example of this

Answer 7

Individuals with same mutations manifest disease differently

Example= neurofibromatosis

Individuals appear to be disease free despite having both ancestors carrying mutant gene

Question 8

What is anticipation?

Answer 8

• age at onset is lower and/or severity worse in successive generations
• Older the father, the less stable the HD disease becomes

Question 9

Give an example of an autosomal dominant condition with reduced penetrance.

Answer 9

Example 2: Retinoblastoma
Mutation

Obligate carrier- mother is a carrier but gene not expressed and is expressed in offspring

With reduced penetration

90% penetrance- 90% manifest the disorder

Due to epigenetics, some people with the gene wont express the disease

Autosomal dominant

Question 10

HD

Answer 10

Example 3: HD
Age dependent penetrance
Progressive neurodegenerative disease 
Trinucleotide repeat (CAG) in huntingdon gene
Which encodes glutamine
stable repeat number is 6 - 35
unstable repeat number is 36 - >100
Example of reduced penetrance
Larger PCR- most repeats, run through gel slower
Anticipation

Question 11

a) How will daughter cells differ if nondisjunction occurs in meiosis 2?​
b) what are the different combinations of gametes that can arise?

Answer 11

a) disomic gamete
Nullisomic gamete

b) disomic + normal gamete = trisomic conceptus

nullisomic + normal gamete= monosomic conceptus

disomic + nullisomic= uniparental disomy

Question 12

What are the mechanisms by which mosaicim occurs?

Answer 12

1. Postzygotic nondisjunction in an initially normal conceptus can lead to mosaicism – e.g. 46,N/47,+21​
   ​
2. Anaphase lag in an initially abnormal 47,+21 conceptus; e.g. 46,N/47,+21