Midterm 1 - Notes 4 (Part 5)

Question 1

In the genome-wide associations of HPFH phenotype what were they looking for?

Answer 1

They looked for associations and linkages between alleles

- found 3

Question 2

Where were the associations/ linkages found? (3)

Answer 2

1. Close to the fetal (and human) Hb locus itself

2. Locus close to HBS1L/MYB

Question 3

MYB

Answer 3

Known transcriptional regulator of HbF expression

Question 4

HBS1L (2)

Answer 4

1. Belongs to G protein family

2. Known to be associated with HbF

Question 5

When do associations become undetectable?

Answer 5

When they are about 50kb away in either direction

- this is what we expected

Question 6

Those who have high HbF levels have low levels of what?

Answer 6

Thalassemia levels

Question 7

What do SNP locus that are associated with > 0.8% HbF also associated with?

Answer 7

With better health among beta-thalassemia patients

Question 8

Higher levels of HbF is negatively correlated with what?

Answer 8

Symptom severity

Question 9

Where is HbF located?

Answer 9

Chromosome 11

Question 10

Where are the SNPs associated with HbF levels found?

Answer 10

Chromosome 2

Question 11

What does HbF gene on chromosome 11 cause?

Answer 11

The phenotype differences

Question 12

What does the locus control region allow?

Answer 12

High expression of genes in a cluster

Question 13

Cis-elements and trans-acting factors (2)

Answer 13

1. Some are common for all the genes

2. Other are specific for individual genes

Question 14

What does BCL11A cause?

Answer 14

Polymorphism

- must be close to the linkage gene, otherwise the linkage would drop really fast on either side

Question 15

What is BCL11A known to be involved in?

Answer 15

Lymphocyte development

Question 16

BCL11A

Answer 16

B-Cell Lymphoma/Leukemia 11A

Question 17

When BCL11A is mutated, what does it lead to?

Answer 17

Leukemia

Question 18

What is BCL11A normally necessary for?

Answer 18

The development of lymphocytes (WBC)

Question 19

What can zinc fingers be?

Answer 19

Transcription factors

Question 20

What do zinc fingers do?

Answer 20

Encodes transcription factor gene regulatory factor

Question 21

Zinc fingers

Answer 21

Is a class of DNA binding domains

Question 22

What are zinc fingers named after?

Answer 22

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

Question 23

What are zinc finger domains involved with?

Answer 23

The interaction with other proteins and DNA

Question 24

What was the 2 hypothesis for the Sankaran et al., study?

Answer 24

1. BCL11A gene encodes a stage-specific regulator of HbF expression
2. The mutation (thats linked to the SNP) influences BCL11A’s ability to turn HbF transcription on or off

Question 25

Where was protein extracted from in BCL11A study?

Answer 25

Adult erythroid precursors

Question 26

What does BCL11A negatively correlate with?

Answer 26

Hb levels

• the higher BCL11A is the less Hb levels there are (and vice versa)
• its a negative regulator

Question 27

IP

Answer 27

Immunoprecipitation

Question 28

Immunoprecipitation

Answer 28

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

Question 29

How did they confirm there findings?

Answer 29

By other independent experiments

Question 30

Where is BCL11A expressed?

Answer 30

RBC precursors

Question 31

Does BCL11A influence HbF gene expression?

Answer 31

Yes

Question 32

What does BCL11A repress?

Answer 32

HbF

Question 33

What is the result when there is less BCL11A?

Answer 33

There is more HbF

Question 34

Can BCL11A bind to HbF cis element?

Answer 34

Yes