Lecture 2 GiM

Question 1

What is complex/multifactorial genetic disorders?

Answer 1

The interaction of multiple genes (genetic predisposition) in combination with environmental factors

Question 2

What is the example of complex/multifactorial genetic disorders?

Answer 2

Type II diabetes and Ischemic heart disease

Question 3

What is the example of single gene inheritance disease?

Answer 3

Cystic fibrosis

Question 4

Identify 5 different types of genetic disorders?

Answer 4

Multifactorial/Complex, Single gene, Chromosomal, Mitochondria and Somatic mutations

Question 5

Identify 4 different types of single genes mode of inheritance

Answer 5

Autosomal Dominance
Autosomal Recessive
X-linked
Mitochondrial

Question 6

Identify the characteristic of Autosomal Dominance inheritance pattern

Answer 6

Males and females equally affected

Offspring of affected person has a 50% chance of inheriting the condition

Question 7

What are the example of diseases caused by Autosomal Dominance inheritance pattern?

Answer 7

Myotonic dystrophy
Marfan syndrome
Huntington disease

Question 8

What is penetrance

Answer 8

The frequency with which a specific genotype is expressed by those individuals that possess it, usually given as a percentage.

Question 9

What is incomplete penetrance?

Answer 9

Not all relatives who inherit the mutation develop the disorder – eg BRCA1 mutations 80% life time chance of developing breast cancer

Question 10

What is Expressivity?

Answer 10

The extent to which a heritable trait is manifested by individual

Question 11

What are the symptoms of Marfan Syndrome?

Answer 11

Aortic dilatation, lens dislocation, stretch marks

Question 12

BRCA1 and BRCA2 mutation increased the susceptibility of what type of diseases?

Answer 12

Ovarian and breast cancer

Question 13

What is anticipation?

Answer 13

The symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next.
In most cases, it also increase the severity of the diseases too.

Question 14

What is de novo/new dominant mutation?

Answer 14

A new mutation that has occurred during gametogenesis or in early embryonic development.

Question 15

What are the patterns of Autosomal Recessive inheritance?

Answer 15

Disease seen in one generation (typically not seen in every generation of an affected family)
Parents usually unaffected
Offspring of affected individual has low risk of disease – unless in consanguineous relationship
Relatives may be asymptomatic carriers of the disease
Affects males and females equally
Gene mutations, not chromosomes

Question 16

What are the example of diseases that follow Autosomal Recessive inheritance pattern?

Answer 16

Cystic fibrosis
Many of the metabolic disorders
Haemachromatosis
Sickle cell disease

Question 17

What are the patterns of X-linked inheritance?

Answer 17

Males affected
Females may be unaffected, mildly through to fully affected
Males usually more severely affected than females
Can NOT have male to male transmission
Gene mutations and chromosome deletions/ duplications

Question 18

What are the example of X-linked inherited diseases?

Answer 18

Duchenne Muscular dystrophy,
Fragile X syndrome
Red / green colour-blindness
Haemophilia

Question 19

For X-linked inheritance pattern, why females have such a variable phenotype?

Answer 19

Due to 2 factors:

• X inactivation
• X-linked dominance vs X-linked recessive inheritance

Question 20

Can you predict female phenotype accurately in prenatal testing?

Answer 20

No

Question 21

What is X-inactivation?

Answer 21

The process of random inactivation of one of the X chromosomes in cells with more than one X chromosome.
Compensates for the presence of the double X gene dose.

Question 22

What is characteristic of X-inactivation?

Answer 22

Is normal and occurs when there is 2 or more X chromosomes in a cell
Occurs in early embryogenesis
Random – which X is silenced
Once inactivated an X-chromosome remains inactive throughout the lifetime of the cell and all its descendants
Most, but not all genes switched off on the inactivated X

Question 23

What is the percentage of cells which express the normal gene?

Answer 23

Approximately 50%

Question 24

What is the preference for X-inactivation?

Answer 24

random preference for “normal” X chromosome to be inactivated (skewed X-inactivation)

Question 25

What is the example of X-linked inheritance?

Answer 25

Rett syndrome (lethal in males, phenotype only in females)
Fragile X syndrome – females:- asymptomatic to fully symptomatic ( due to X-inactivation pattern)

Question 26

What is the example of X-linked recessive?

Answer 26

Red-green colour blindness
Haemophilia
Duchene Muscular dystrophy
Carrier girls usually unaffected BUT can have significant symptoms because of X-inactivation (switches off normal X)
Girls fully affected if inherit mutation from mum and dad

Question 27

What is the example of disease that follow mitochondrial inheritance pattern?

Answer 27

Maternally inherited diabetes and deafness

Question 28

Where does human inherit their mitochondria from?

Answer 28

Their mother (the sperm does not any mitochondria)

Question 29

What are the characteristic of mitochondrial inheritance pattern?

Answer 29

Rare, males and females affected equally
Only 27 genes within mitochondrial DNA
Each cell has many mitochondria
Every mitochondrium has many copies of each gene
Mitochondria are inherited from the mother’s egg
An affected mother will give all her children the mutation
Highly variable expressivity and therefore severity of phenotype between relatives
All the children of an affected man will be unaffected