Genetic Basis of Human Disease

Question 1

What is a Mendelian disorder?

Answer 1

A disorder that is inherited due to a mutation at a single locus

Question 2

Example of an autosomal recessive disorder

Answer 2

Alkaptonuria

Question 3

If both parents are heterozygous carriers of the alkaptonuria mutation, what are the chances of their offspring having alkaptonuria?

Answer 3

25%

Question 4

What is alkaptonuria?

Answer 4

Defect in the enzyme homogentisate-1,2-dioxygenase (HGD) –> body can’t process tyrosine or phenylalanine

Question 5

What can’t the body process if you have alkaptonuria?

Answer 5

Tyrosine or phenylalanine

Question 6

Example of an autosomal co dominant disorder

Answer 6

Sickle cell anaemia

Question 7

What is an autosome?

Answer 7

Any chromosome that isn’t a sex chromosome

Question 8

What is sickle cell anaemia caused by?

Answer 8

A single point mutation in amino acid 6 of the ß-globin subunit of haemoglobin…. Glutamate –> Valine

Question 9

What amino acid is altered in sickle cell anaemia?

Answer 9

Glutamate –> Valine

Question 10

How can being a heterozygous carrier of sickle cell anaemia help you?

Answer 10

Individuals who are heterozygous carriers exhibit sickle cell trait but exhibit increased resistance to malaria

Question 11

How is sickle cell anaemia a co dominant disorder?

Answer 11

The alleles exhibit co dominance as the heterozygote sickle cell phenotype is an intermediate between the wild-type and sickle cell

Question 12

What is karyotyping?

Answer 12

A method which allow distinguishing chromosomes by band patterning and length

Question 13

What do abnormalities in banding show? (karyotyping)

Answer 13

Shows mutagenic rearrangements have taken place with can then be associated with specific phenotypes

Question 14

Karyotyping enables…

Answer 14

…genes to be mapped to specific chromosomal locations

Question 15

Example of autosomal dominant disorders

Answer 15

• Aniridia
• Brachydactyly
• Huntington’s disease

Question 16

What is anirida?

Answer 16

Absence of an iris

Question 17

What causes aniridia?

Answer 17

Loss-of-function or deletion mutation in one allele of the gene on chromosome 5

Question 18

What happens if there are no alleles present in anridia?

Answer 18

It’s embryonic lethal so death

Question 19

Which gene is associated with aniridia?

Answer 19

PAX6

Question 20

What is brachydactyly?

Answer 20

Shortened digits

Question 21

What is Huntington’s disease?

Answer 21

A neurodegenerative disorder in which there is neuronal loss in the basal ganglia and dilation of the lateral ventricles

Question 22

Which gene is associated with Huntington’s disease?

Answer 22

Huntingtin

Question 23

What does the mutation in Huntington’s disease cause?

Answer 23

Alters the number of CAG repeats which relates to the disease expression. Expansion of the polyQ tract. Huntingtin toxic to neurons

Question 24

What is the protein huntingtin associated with?

Answer 24

Synaptic vesicle dynamics and neurotransmitter release

Question 25

Example of X-linked disorder

Answer 25

• Haemophilia

- Duchenne muscular dystrophy (DMD)

Question 26

What is DMD?

Answer 26

Duchenne muscular dystrophy, a progressive muscle damage and muscle wasting disease

Question 27

What is the biggest gene known to humans?

Answer 27

Dystrophin

Question 28

Which gene is associated with Duchenne muscular dystrophy?

Answer 28

Dystrophin

Question 29

What genetic difference is there between a patient with DMD and someone without?

Answer 29

Patient with DMD has a region on their X chromosome missing

Question 30

Where can the DMD gene be located?

Answer 30

Xp21

Question 31

How was the DMD gene identified?

Answer 31

It was identified by a DNA sequence on the X chromosome that was deleted

Question 32

What accumulates in joints in alkaptonuria?

Answer 32

Homogentisic acid