Midterm 1 - Notes 4 (Part 5) Flashcards
In the genome-wide associations of HPFH phenotype what were they looking for?
They looked for associations and linkages between alleles
- found 3
Where were the associations/ linkages found? (3)
- Close to the fetal (and human) Hb locus itself
2. Locus close to HBS1L/MYB
MYB
Known transcriptional regulator of HbF expression
HBS1L (2)
- Belongs to G protein family
2. Known to be associated with HbF
When do associations become undetectable?
When they are about 50kb away in either direction
- this is what we expected
Those who have high HbF levels have low levels of what?
Thalassemia levels
What do SNP locus that are associated with > 0.8% HbF also associated with?
With better health among beta-thalassemia patients
Higher levels of HbF is negatively correlated with what?
Symptom severity
Where is HbF located?
Chromosome 11
Where are the SNPs associated with HbF levels found?
Chromosome 2
What does HbF gene on chromosome 11 cause?
The phenotype differences
What does the locus control region allow?
High expression of genes in a cluster
Cis-elements and trans-acting factors (2)
- Some are common for all the genes
2. Other are specific for individual genes
What does BCL11A cause?
Polymorphism
- must be close to the linkage gene, otherwise the linkage would drop really fast on either side
What is BCL11A known to be involved in?
Lymphocyte development
BCL11A
B-Cell Lymphoma/Leukemia 11A
When BCL11A is mutated, what does it lead to?
Leukemia
What is BCL11A normally necessary for?
The development of lymphocytes (WBC)
What can zinc fingers be?
Transcription factors
What do zinc fingers do?
Encodes transcription factor gene regulatory factor
Zinc fingers
Is a class of DNA binding domains
What are zinc fingers named after?
Specific domains that are combined by the presence of a zinc atom that coordinates the part of the protein in a fashion that 2 histomines and cistines form a finger like structure
What are zinc finger domains involved with?
The interaction with other proteins and DNA
What was the 2 hypothesis for the Sankaran et al., study?
- BCL11A gene encodes a stage-specific regulator of HbF expression
- The mutation (thats linked to the SNP) influences BCL11A’s ability to turn HbF transcription on or off
Where was protein extracted from in BCL11A study?
Adult erythroid precursors
What does BCL11A negatively correlate with?
Hb levels
- the higher BCL11A is the less Hb levels there are (and vice versa)
- its a negative regulator
IP
Immunoprecipitation
Immunoprecipitation
Is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein
- this process can be used to isolate and concentrate a particular protein from a sample containing many thousands of different proteins
How did they confirm there findings?
By other independent experiments
Where is BCL11A expressed?
RBC precursors
Does BCL11A influence HbF gene expression?
Yes
What does BCL11A repress?
HbF
What is the result when there is less BCL11A?
There is more HbF
Can BCL11A bind to HbF cis element?
Yes
