Midterm 1 - Notes 4 (Part 3)

Question 1

What was looked for in the clubfoot study?

Answer 1

Looked for copy number variations

- not SNP variations

Question 2

What do CNV target?

Answer 2

They target to detect the presence of absence of LARGER AREAS of the genome

Question 3

What are CNVs used for?

Answer 3

Used to identify deletions or insertions in the genomic DNA

Question 4

CNV

Answer 4

Copy Number Variation

Question 5

Copy number variation

Answer 5

Is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals in the human population

Question 6

What ratio and log ratio do you get if you have a duplication of a particular region?

Answer 6

• Ratio = 2:1

- Log ratio = 1

Question 7

What do you get when the log2 ratio is lower than 0?

Answer 7

Gene loss

Question 8

What do test and control tissues provide?

Answer 8

They provide genomic DNA

- needs to be isolated first and then labelled

Question 9

When analyzing results how do you know when DNA is present a lot?

Answer 9

The intensity of the fluorescence will be strong

Question 10

What does it mean when you have a log2 result of -1?

Answer 10

Then you know that it contains half the number region compared to a normal individual
- results in a heterozygous deletion because you lose one copy

Question 11

What happens if you lose Pitx1 deletion is in both genes?

Answer 11

Lethal

Question 12

Why do you need to be carful when testing a small sample size?

Answer 12

It is easier to develop false positive results

Question 13

Haplionsufficiency

Answer 13

Is a mechanism of action to explain a phenotype when a diploid organism has lost one copy of that gene

Question 14

What does haplionsufficiency cause?

Answer 14

Causes the effect on leg development

Question 15

What is haplionsufficiency caused by?

Answer 15

Caused by loss of function mutation and cant produce enough normal wild type phenotype

Question 16

What normally happens to homozygous Pitx1-/- animals?

Answer 16

They die before or shortly after birth with severe hind limb development

Question 17

What normally happens to heterozygous Pitx1+/-?

Answer 17

No obvious phenotype

• can live (not lethal)
• -> but had to re-examine because it wasnt matching with what they observed

Question 18

What did they find when they re-evaluated the heterozugous Pitx1+/- animals?

Answer 18

They found that 8.9% of Pitx1+/- actually showed club foot phenotypes

Question 19

What were the 2 similar phenotypes in humans and in mice with Pitx1+/-?

Answer 19

1. Bone aberrations

2. Volume reduction

Question 20

What 2 things were reduced in the humans and mice with Pitx1+/-?

Answer 20

1. Artery development

2. Muscle development

Question 21

What increased in humans and mice with Pitx1+/-?

Answer 21

Fat incorporation

Question 22

What can losing one copy of Pitx1 effect in both mice and humans?

Answer 22

Hind limb development and leg development formation

Question 23

What happens if you have a lot of markers?

Answer 23

1. Better results

2. Able to compare less related organisms

Question 24

What happened to recombinant generations as the alleles got further away?

Answer 24

More recombinant generations occurred

Question 25

What could happen in F3 if F2 individuals were allowed to mate randomly? (2)

Answer 25

1. Co-inherited haploblocks became smaller

2. Linkage only detectable in closely linked markers

Question 26

What happens when you have more generations?

Answer 26

You get smaller blocks and more cross overs occur

• the more the cross over the smaller the blocks
• linkages are not as strong

Question 27

What does 50/50 linkage mean?

Answer 27

Independent sorting

- start its own linkage group

Question 28

What happens if natural population was being used?

Answer 28

1. Last common ancestor many generations ago
2. Very small haplotype blocks
   - Makes it harder to use because the get smaller and smaller

Question 29

Genome wide associations

Answer 29

Look at many markers across genome and find co-segregation

Question 30

What is Beta-thalassemia?

Answer 30

Fetal hemoglobin

Question 31

Anemia

Answer 31

Insufficient amounts of healthy RBC

Question 32

What is hemoglobins main function?

Answer 32

Transports oxygen throughout the body in mammals

Question 33

What is hemoglobin altered by?

Answer 33

Deficiencies in iron and vitamin B12

- doesnt allow proper development of RBC becasue the proper precursors are not there

Question 34

What is an example of genetic anemia?

Answer 34

Sickle cell disease

- is effected by mutated hemoglobin

Question 35

Sickle cell disease is caused by what mutation?

Answer 35

Mutation in the beta globin gene