Midterm 1 - Notes 4 (Part 5) Flashcards

1
Q

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

A

They looked for associations and linkages between alleles

- found 3

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2
Q

Where were the associations/ linkages found? (3)

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

2. Locus close to HBS1L/MYB

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3
Q

MYB

A

Known transcriptional regulator of HbF expression

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4
Q

HBS1L (2)

A
  1. Belongs to G protein family

2. Known to be associated with HbF

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5
Q

When do associations become undetectable?

A

When they are about 50kb away in either direction

- this is what we expected

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6
Q

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

A

Thalassemia levels

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7
Q

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

A

With better health among beta-thalassemia patients

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8
Q

Higher levels of HbF is negatively correlated with what?

A

Symptom severity

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9
Q

Where is HbF located?

A

Chromosome 11

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10
Q

Where are the SNPs associated with HbF levels found?

A

Chromosome 2

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11
Q

What does HbF gene on chromosome 11 cause?

A

The phenotype differences

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12
Q

What does the locus control region allow?

A

High expression of genes in a cluster

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13
Q

Cis-elements and trans-acting factors (2)

A
  1. Some are common for all the genes

2. Other are specific for individual genes

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14
Q

What does BCL11A cause?

A

Polymorphism

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

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15
Q

What is BCL11A known to be involved in?

A

Lymphocyte development

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16
Q

BCL11A

A

B-Cell Lymphoma/Leukemia 11A

17
Q

When BCL11A is mutated, what does it lead to?

18
Q

What is BCL11A normally necessary for?

A

The development of lymphocytes (WBC)

19
Q

What can zinc fingers be?

A

Transcription factors

20
Q

What do zinc fingers do?

A

Encodes transcription factor gene regulatory factor

21
Q

Zinc fingers

A

Is a class of DNA binding domains

22
Q

What are zinc fingers named after?

A

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

23
Q

What are zinc finger domains involved with?

A

The interaction with other proteins and DNA

24
Q

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

A
  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
25
Where was protein extracted from in BCL11A study?
Adult erythroid precursors
26
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
27
IP
Immunoprecipitation
28
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
29
How did they confirm there findings?
By other independent experiments
30
Where is BCL11A expressed?
RBC precursors
31
Does BCL11A influence HbF gene expression?
Yes
32
What does BCL11A repress?
HbF
33
What is the result when there is less BCL11A?
There is more HbF
34
Can BCL11A bind to HbF cis element?
Yes