2. Mrs Jones (2) - risk of transmission of disease

Question 1

Monogenic

Answer 1

Clear inheritance
No environmental influence
Rare

Question 2

Give 3 examples of monogenic diseases

Answer 2

Huntington disease
Cystic fibrosis
Haemophilia

Question 3

Complex disorders

Answer 3

No clear inheritance
Environment essential
Common

Question 4

Complex disorders examples

Answer 4

Type 2 diabetes, Schizophrenia, Crohn’s disease

Question 5

Mendelian Inheritance

Answer 5

Individuals inherit and transmit to their offspring 1 out of the 2 alleles present in homologous chromosomes

Question 6

Allele

Answer 6

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

Question 7

Homologous chromosomes

Answer 7

matching (but non-identical) pair of chromosomes -

1 from each parent

Question 8

Different alleles maybe described as

Answer 8

MUTATIONS or POLYMORPHISMS

Question 9

Mutation

Answer 9

any heritable change in the DNA sequence

Question 10

Polymorphism

Answer 10

a mutation at a >1% frequency in a given population

Question 11

Polymorphisms are usually still called mutations if

Answer 11

they cause monogenic disease

Question 12

Point Mutations

Answer 12

A single change in the DNA sequence:
Missense
Nonsense
Frameshift

Question 13

Missense mutation

Answer 13

Codon changes to code for a different amino acid

Question 14

Nonsense mutation

Answer 14

Codon codes for a stop codon so polypeptide chain ends prematurely

Question 15

Frame-shift Mutations

Answer 15

Insertion/ Deletion of an extra base will cause the code to be shifted out of frame

Question 16

Why take a genetic family history?

Answer 16

Identify genetic disease in a family
Identify inheritance patterns
Aid diagnosis
Assist in management of conditions
Identify relatives at risk of disease

Question 17

5 Types of Mendelian Inheritance Patterns

Answer 17

Autosomal Dominant 
Autosomal Recessive 
X-linked Dominant (RARE) 
X-linked Recessive 
Mitochondrial

Question 18

Parent in Autosomal Dominant

Answer 18

At least 1 affected parent

Question 19

Who can transmit or be affected by Autosomal Dominant diseases?

Answer 19

Transmitted by M or F

M or F affected

Question 20

Chance of child being effected in Autosomal Dominant pattern

Answer 20

50%

Question 21

Example of Autosomal Dominant disease

Answer 21

Huntington’s Disease

Question 22

Huntington’s Disease

Answer 22

Motor, Cognitive and Psychiatric dysfunction - hyperkinesia
Age of Onset: 35 - 44 years
Survival Time: 15 - 18 years after onset (no cure)

Question 23

Huntington’s Disease Mechanism

Answer 23

1. HTT gene on Chr 4 encodes huntingtin protein.
2. HD patient inherit 1 copy of a mutated form of the huntingtin gene.
3. Altered gene encodes a toxic form of the protein that forms ‘clumps’.
4. Cell death in basal ganglia of brain resulting in symptoms.

Question 24

Patterns of inheritance with Huntington’s Disease

Answer 24

Age of Onset Decreases

Severity Increases

Question 25

Molecular basis of Huntington's Disease

Answer 25

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

Question 26

Parent and Family history in Autosomal recessive

Answer 26

No affected parent | Usually no family history

Question 27

Chance of child being effected in Autosomal recessive pattern

Answer 27

25% risk of child being effected | 50% chance of child being carrier

Question 28

Example of Autosomal recessive disease

Answer 28

Cystic Fibrosis

Question 29

Cystic Fibrosis symptoms

Answer 29

Thick mucus in lungs causes breathing problems and repeated infections. Blockages in pancreas affect digestive enzymes Chronic, life threatening condition

Question 30

Cystic Fibrosis Mechanism

Answer 30

1. CFTR gene on Chr 7 encodes Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. 2. CF patients inherit 2 copies of mutated CFTR gene. 3. Absence of functional CFTR protein affects chloride ion function in epithelial cells. 4. Disruption of Salt/Water regulation causes thick mucus & leads to symptoms

Question 31

What is the most common mutation causing CF?

Answer 31

ΔF508 | Deletion affects folding of CFTR protein and prevents it moving to correct place in cell membrane

Question 32

Congenital Absence of the Vas Deferens (CAVD) is a condition in which vasa deferentia fail to form properly, what does it cause?

Answer 32

``` Causes infertility (azoospermia) Affects 1/2500 men ```

Question 33

Whats the most common cause of CAVD?

Answer 33

MUTATIONS IN CFTR GENE

Question 34

Parent in X-Linked Recessive

Answer 34

No affected parents

Question 35

Who is effected in X-linked recessive?

Answer 35

Males

Question 36

Who transmits X-linked recessive diseases?

Answer 36

Carrier females

Question 37

X-linked recessive probabilities

Answer 37

Sons have a 50% risk of being affected | Daughters have a 50% chance of being a carrier

Question 38

X-linked recessive example

Answer 38

Haemophilia

Question 39

Haemophilia

Answer 39

Blood clotting disorder: affected bruise easily and bleed longer 2 main types: A and B

Question 40

Haemophilia Mechanism

Answer 40

1. F8 gene on Chr X encodes coagulation factor VIII protein 2. Boys with haemophilia A inherit 1 copy of a mutated form of the F8 gene. 3. Lack of functioning Factor VIII causes symptoms of disorder

Question 41

What causes Haemophilia B?

Answer 41

Mutations in F9 gene - also on X chromosome. | F9 codes for coagulation factor IX

Question 42

Haemophilia A and B symptoms

Answer 42

ARE IDENTICAL | Haemophilia B is much rarer

Question 43

Same gene Different mutation Different symptoms

Answer 43

CF and CAVD | both caused by mutations to CFTR gene

Question 44

Same disease | Different genes

Answer 44

Haemophilia A and B

Question 45

Same disease Different genes Different inheritance patterns

Answer 45

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

Question 46

Incomplete Penetrance

Answer 46

Symptoms NOT always present in an individual with a disease-causing mutation

Question 47

Variable Expressivity

Answer 47

Disease severity may vary between individuals with same disease-causing mutation

Question 48

Phenocopy

Answer 48

having same disease but with a different underlying cause

Question 49

Epistasis complications

Answer 49

Interactions between disease gene mutations and other modifier genes can affect phenotype

Question 50

Epistasis

Answer 50

a type of gene action in which 1 gene can suppress action of another (nonallelic) gene

Question 51

Molecular mechanism of dominant conditions

Answer 51

usually caused by gene mutations that result in toxic protein (e.g. HD) - effects of the mutated gene ‘MASK’ the normal copy

Question 52

Molecular mechanism of recessive conditions

Answer 52

caused by mutations that result in absence of functional protein (e.g. CF, Haemophilia) - effects of mutated gene only seen because normal copy is absent

Question 53

Molecular mechanism of co-dominant conditions

Answer 53

effects of both mutated and normal genes apparent in people with both e.g. Sickle Cell Trait

Question 54

Implications for treatment: | Dominant & Co-dominant Conditions

Answer 54

Need to neutralise effects of the toxic protein or switch off mutant gene to UNMASK the normal gene

Question 55

Implications for treatment: | Recessive Conditions

Answer 55

Need to restore activity of missing protein by replacing gene or protein product or even affected tissues

Question 56

Square in genetic pedigree

Answer 56

Male

Question 57

Circle in genetic pedigree

Answer 57

Female

Question 58

Coloured in symbol in genetic pedigree

Answer 58

Affected individual

Question 59

Bottom left to top right diagonal line through symbol in genetic pedigree

Answer 59

Deceased