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Flashcards in Genetics 2 Deck (30)
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1
Q

Highlight some differences between monogenic diseases and complex disorders.

A

Monogenic

  • Clear inheritance
  • No environmental influence
  • Rare
  • eg Huntington Disease, CF, Haemophilia

Complex Disorders

  • No clear inheritance
  • Environment essential
  • Common
  • e.g. Type 2 Diabetes, Schizophrenia, Crohn’s disease
2
Q

What is mendelian inheritance?

A

Process whereby individuals inherit and transmit 1 out of 2 alleles present in homologous chromosomes to their offspring

3
Q

What is an allele?

A

Alternate form of a gene/DNA sequence AT THE SAME LOCUS

4
Q

Different alleles may be described as ………… or ………..

A

Mutations or polymorphisms

5
Q

What is the difference between mutation and polymorphism?

A

Mutation - any heritable change in DNA sequence

Polymorphism - mutation that >1% frequency in a given population

POLYMORPHISMS are still usually called mutations if they contribute to monogenic disease.

Polymorphisms may contribute to complex diseases

6
Q

Missense mutation vs Nonsense mutation?

THESE ARE BOTH POINT MUTATIONS

A

Missense - codon changes for different aa

Nonsense - codon changes for a stop codon. Polypeptide chain ends prematurely

7
Q

What are the 5 types of Mendelian Inheritance patterns?

A
  1. Autosomal dominant
  2. Autosomal recessive
  3. X-linked dominant
  4. X-linked recessive
  5. Mitochondria

X linked dominant is rare

8
Q

Describe autosomal dominant.

A
  1. At least one parent is affected

2. 50% risk of each child being affected

9
Q

Huntingtons disease?

A
  1. It is autosomal dominant.
  2. Motor, cognitive and psychiatric dysfunction
  3. Onset 35-44 years
  4. Survival is 15-18 years after onset

MECHANISM:

  1. HTT gene on Chr 4 encodes Huntingtin
  2. HD patients inherit one mutated copy of HTT gene
  3. Mutated gene encodes toxic form of protein - forms “clumps”
  4. Causes cell death in basal ganglia giving rise to symptoms.
10
Q

What are the patterns of inheritance with Huntingtons? (GENETIC ANTICIPATION)

A
  1. Age of onset decreases as you go down the family tree

2. Severity increases

11
Q

What is the molecular basis for Huntingtons?

A

Unstable CAG triplet repeat
Number of repeats may increase with each generation
More repeats = more likely to be affected

12
Q

Describe Autosomal recessive.

A
  1. No affected parent
  2. Usually no family history
  3. 25% risk of child being infected, 50% risk of child being a carrier
13
Q

Describe CF.

A
  1. Cystic Fibrosis is an autosomal recessive condition
  2. Thick mucus in lungs causes breathing problems
  3. Blockages in pancreas may affect digestive enzymes

MECHANISM:

  1. CFTR gene encodes CFTR protein (CF transmembrane conductance regulator)
  2. CF patients inherit 2 copies of a mutated form of CFTR gene
  3. No functional CFTR protein means Cl- channels affected in epithelial cells.
  4. Salt/water regulation disrupted, which causes thick mucus
14
Q

What is the molecular basis for CF?

A

Many different mutations identified (>!500)

Most common is delta F508.

Deletion affects folding of CFTR protein

15
Q

What else can mutations in the CFTR gene do?

A

It can cause infertility, due to Congenital Absence of the Vas Deferens (CAVD), causing azoospermia.

16
Q

Describe X linked recessive conditions.

A
  1. No affected parents
  2. Only males usually affected
  3. Transmitted by female carrier
  4. Sons have a 50% chance of infection
  5. Daughters have 50% chance of carrying
17
Q

Describe haemophilia.

A
  1. X linked disease.
  2. Blood clotting disorder
  3. There are 2 types: A and B
  4. Treated successfully with injections of clotting factor

MECHANISM:

  1. Haemophilia A is caused by boys inheriting one mutated copy of the F8 gene.
  2. The F8 gene on Chr X encodes coagulation factor 8.
  3. Haemophilia B is caused by F9 mutation (Chr X).
  4. F9 codes for coagulation factor 9.
  5. Identical symptoms to Haemophilia A, but haemophilia B is much rarer.
18
Q

Give an example of same gene, different disease.

A

CFTR - cystic fibrosis (delta F508) or vas deferens

19
Q

Give an example of same disease, different genes.

A

Haemophilia A and B.

20
Q

Give an example of same disease, different genes and different inheritance pattens.

A

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

21
Q

What is meant by incomplete penetrance?

A

Symptoms not always present with people who have disease causing mutation

22
Q

What is meant by variable expressivity?

A

Disease severity may vary between individuals with same disease causing mutation

23
Q

Both incomplete penetrance and variable expressivity are features of ………. inheritance.

A

Dominant

24
Q

What is phenocopy?

A

Having the same disease with different underlying causes

25
Q

Epistasis?

A

Interactions between the disease gene mutation and other modifier genes can affect the phenotype.

26
Q

What are the general molecular mechanisms of Dominant conditions?

A

They’re usually gene mutations coding for toxic proteins.

Mutated gene effects mask the normal gene

27
Q

What are the general molecular mechanisms of recessive conditions?

A

They’re usually caused by the absence of a functional protein.

Effects of mutated gene only seen because normal gene absent

28
Q

What is the mechanism of codominant conditions.

A

Effects of both the normal and mutated genes are present (e.g. sickle cell)

29
Q

How do you treat dominant//codominant conditions?

A

NEUTRALISE effects of toxic protein or SWITCH OFF mutant gene to unmask normal gene

30
Q

How do you treat recessive conditions?

A

RESTORE activity of missing protein - either replace the gene or the protein product or the affected tissues