gene expression and human disease Flashcards
What is Fragile-X syndrome caused by?
- expansion of CGG results in methylation of DNA in promotor
- prevents RNA polymerase complex assembling properly
What are some symptoms of Fragile-X syndrome?
- large, protruding ears
- learning difficulties
- macro-orchidism
- double-jointed thumbs
- hyperextensible finger joints
What are the 3 types of RNA polymerase?
RNA polymerase I, II, III
Which genes does RNA polymerase I transcribe?
most rRNA genes
Which genes does RNA polymerase II transcribe?
- protein-coding genes
- miRNA genes
- genes for some small RNAs
Which genes does RNA polymerase III transcribe?
- tRNA genes
- 5S rRNA genes
- many small RNAs
How is RNA polymerase III related to cancer?
the amount of RNA polymerase III often increases during cancer progression
What starts transcription?
- basal transcription factors bind first
- RNA polymerase binds with other factors
What makes RNA polymerase start once binded?
phosphorylation of the C-terminal domain on RNA polymerase
Why may DNA sometimes seem to loop around in trancription?
for some regulatory transcription factors to bind
What is a disease that is an example of a lack of transcription of a particular gene?
- fragile-X syndrome
- expansion of CGG results in methylation of DNA in the promoter, preventing RNA polymerase complex from assembling properly
What are some symptoms of Fragile-X syndrome?
- large protruding ears
- hyperextensible finger joints
- double-jointed thumbs
- macro-orchidism
- learning difficulties/autism
What is an example of the clinical effects caused by lack of transcription on a number of genes?
- mutations in ATRX results in alpha-thalassemia (deficiency of alpha-globin) and mental retardation
How do the mutations in ATRX affect people?
- ATRX is a protein that unwinds DNA, it is associated with centromeres
- lack of ATRX shuts down transcription of number of genes
What happens to the mRNA strand after transcription?
C-terminal domain acts as assembly line to co-ordinate modifications of capping, splicing, polyadenlyation
What is meant by capping and polyadenlyation?
- adding a 5’ cap
- adding a poly A tail
How are introns removed?
- by a complex of RNAs and proteins called the spliceosome
- accuracy is conferred by small nuclear RNA (snRNAs) within spliceosome
Give an example of a genetic disease that is due to lack of correct RNA splicing
- beta thalassemia
- cystic fibrosis
What are the symptoms of beta-thalassemia
- anaemia from 6 months of age
What exactly is beta thalassemia caused by?
- introns not spliced out properly
- results in premature stop codons
- lack of protein
How does a lack of correct splicing lead to cystic fibrosis?
exon 9 often skipped leading to loss of function
What is a clinical example of exon skipping?
- Isolated growth hormone deficiency type 2 (IGHD II)
- main symptom is short stature
- dominantly inherited disorder
- mutation in growth hormone gene (GH-1)
