gene expression and human disease

Question 1

What is Fragile-X syndrome caused by?

Answer 1

• expansion of CGG results in methylation of DNA in promotor
• prevents RNA polymerase complex assembling properly

Question 2

What are some symptoms of Fragile-X syndrome?

Answer 2

• large, protruding ears
• learning difficulties
• macro-orchidism
• double-jointed thumbs
• hyperextensible finger joints

Question 3

What are the 3 types of RNA polymerase?

Answer 3

RNA polymerase I, II, III

Question 4

Which genes does RNA polymerase I transcribe?

Answer 4

most rRNA genes

Question 5

Which genes does RNA polymerase II transcribe?

Answer 5

• protein-coding genes
• miRNA genes
• genes for some small RNAs

Question 6

Which genes does RNA polymerase III transcribe?

Answer 6

• tRNA genes
• 5S rRNA genes
• many small RNAs

Question 7

How is RNA polymerase III related to cancer?

Answer 7

the amount of RNA polymerase III often increases during cancer progression

Question 8

What starts transcription?

Answer 8

• basal transcription factors bind first
• RNA polymerase binds with other factors

Question 9

What makes RNA polymerase start once binded?

Answer 9

phosphorylation of the C-terminal domain on RNA polymerase

Question 10

Why may DNA sometimes seem to loop around in trancription?

Answer 10

for some regulatory transcription factors to bind

Question 11

What is a disease that is an example of a lack of transcription of a particular gene?

Answer 11

• fragile-X syndrome
• expansion of CGG results in methylation of DNA in the promoter, preventing RNA polymerase complex from assembling properly

Question 12

What are some symptoms of Fragile-X syndrome?

Answer 12

• large protruding ears
• hyperextensible finger joints
• double-jointed thumbs
• macro-orchidism
• learning difficulties/autism

Question 13

What is an example of the clinical effects caused by lack of transcription on a number of genes?

Answer 13

• mutations in ATRX results in alpha-thalassemia (deficiency of alpha-globin) and mental retardation

Question 14

How do the mutations in ATRX affect people?

Answer 14

• ATRX is a protein that unwinds DNA, it is associated with centromeres
• lack of ATRX shuts down transcription of number of genes

Question 15

What happens to the mRNA strand after transcription?

Answer 15

C-terminal domain acts as assembly line to co-ordinate modifications of capping, splicing, polyadenlyation

Question 16

What is meant by capping and polyadenlyation?

Answer 16

• adding a 5’ cap
• adding a poly A tail

Question 17

How are introns removed?

Answer 17

• by a complex of RNAs and proteins called the spliceosome
• accuracy is conferred by small nuclear RNA (snRNAs) within spliceosome

Question 18

Give an example of a genetic disease that is due to lack of correct RNA splicing

Answer 18

• beta thalassemia
• cystic fibrosis

Question 19

What are the symptoms of beta-thalassemia

Answer 19

• anaemia from 6 months of age

Question 20

What exactly is beta thalassemia caused by?

Answer 20

• introns not spliced out properly
• results in premature stop codons
• lack of protein

Question 21

How does a lack of correct splicing lead to cystic fibrosis?

Answer 21

exon 9 often skipped leading to loss of function

Question 22

What is a clinical example of exon skipping?

Answer 22

• Isolated growth hormone deficiency type 2 (IGHD II)
• main symptom is short stature
• dominantly inherited disorder
• mutation in growth hormone gene (GH-1)