Lecture 16 - Mutations 2

Question 1

What causes Phenylketonuria?

Answer 1

• Caused by an abnormality in a specific enzyme that metabolizes the amino acid phenylalanine. Affected cannot catalyze the conversion of dietary phenylalanine to tyrosine.
• Affected have light hair and skin due to lack of melanin which is made from tyrosine.
• If untreated it leads to learning difficulties.

Question 2

What causes sickle cell anemia?

Answer 2

• In sickle-cell disease, one of the 146 aa in the B-globin chain is different
• Glutamic acid (-vely charged) at position 6 is replaced by valine (hydrophobic).

Question 3

What does sickle-cell anemia cause?

Answer 3

• Abnormal allele produces abnormal hemoglobin that is sickle-shaped and that blocks blood flow in capillaries, leading to tissue damage
• It is autosomal recessive therefore, heterozygotes have sickle cell trait but don’t get the disease.

Question 4

What is aneuploidy?

Answer 4

A chromosomal abnormality where there is either a gain or loss of chromosomes

Question 5

What is fragile-X syndrome?

Answer 5

A constriction at the tip of the X chromosome that is often associated with learning difficulties

Question 6

Explain how fragile-X syndrome occurs

Answer 6

1. The gene responsible for the syndrome, FMR1, contains a repeated triplet, CGC, at a certain point in the promoter region
   1a. In normal people the triplet is repeated 6 to 54 times. In mentally retarded people with the syndrome its repeated 200 to 2000 times.
2. With more than 200 repeats, methylation of the cytosines in the CGC triplets is likely, accompanied by transcriptional inactivation of the FMR1 gene.
   2a. Normally the protein product of this gene is to bind to mRNAs involved in neuron function and regulate their translation at the ribosome.
3. When the FMR1 protein is not made in adequate amounts, there mRNAs are not properly translated, and nerve cells die. Their loss often results in mental retardation

Question 7

Talk about the phenomenon of expanding triplet repeats

Answer 7

It was been found in over a dozen diseases. How these repeats expand is not known; one theory is that DNA polymerase may slip after copying a repeat and then fall back to copy it again.

Question 8

What does it mean for a disease to be multifactorial?

Answer 8

It is caused by interactions between many genes and proteins, and the environment.
*No single mutation causes the disease

Question 9

What are the properties of cancer cells?

Answer 9

1. Uncontrolled growth
2. Often frozen in partially differentiated state
3. Invasive into surrounding tissue
4. Metastatic (migrate to new locations)
5. Clonally derived from progenitor cancel cells with genetic change
6. Often aneuploid or polyploid

Question 10

What is polyploidy?

Answer 10

Cells containing more than two homologous sets of chromosomes

Question 11

What are oncogenes?

Answer 11

Mutated genes that have acquired the ability to confer the hallmarks of cancer
e.g. A growth factor receptor that acquires the ability to drive cell division in the absence of growth factor stimulus

Question 12

What are tumor suppressors?

Answer 12

Genes that help prevent cells becoming cancer cells

e.g. p53 and Rb