Midterm 1 - Notes 4 (Part 3) Flashcards
What was looked for in the clubfoot study?
Looked for copy number variations
- not SNP variations
What do CNV target?
They target to detect the presence of absence of LARGER AREAS of the genome
What are CNVs used for?
Used to identify deletions or insertions in the genomic DNA
CNV
Copy Number Variation
Copy number variation
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
What ratio and log ratio do you get if you have a duplication of a particular region?
- Ratio = 2:1
- Log ratio = 1
What do you get when the log2 ratio is lower than 0?
Gene loss
What do test and control tissues provide?
They provide genomic DNA
- needs to be isolated first and then labelled
When analyzing results how do you know when DNA is present a lot?
The intensity of the fluorescence will be strong
What does it mean when you have a log2 result of -1?
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
What happens if you lose Pitx1 deletion is in both genes?
Lethal
Why do you need to be carful when testing a small sample size?
It is easier to develop false positive results
Haplionsufficiency
Is a mechanism of action to explain a phenotype when a diploid organism has lost one copy of that gene
What does haplionsufficiency cause?
Causes the effect on leg development
What is haplionsufficiency caused by?
Caused by loss of function mutation and cant produce enough normal wild type phenotype
What normally happens to homozygous Pitx1-/- animals?
They die before or shortly after birth with severe hind limb development
What normally happens to heterozygous Pitx1+/-?
No obvious phenotype
- can live (not lethal)
- -> but had to re-examine because it wasnt matching with what they observed
What did they find when they re-evaluated the heterozugous Pitx1+/- animals?
They found that 8.9% of Pitx1+/- actually showed club foot phenotypes
What were the 2 similar phenotypes in humans and in mice with Pitx1+/-?
- Bone aberrations
2. Volume reduction
What 2 things were reduced in the humans and mice with Pitx1+/-?
- Artery development
2. Muscle development
What increased in humans and mice with Pitx1+/-?
Fat incorporation
What can losing one copy of Pitx1 effect in both mice and humans?
Hind limb development and leg development formation
What happens if you have a lot of markers?
- Better results
2. Able to compare less related organisms
What happened to recombinant generations as the alleles got further away?
More recombinant generations occurred
What could happen in F3 if F2 individuals were allowed to mate randomly? (2)
- Co-inherited haploblocks became smaller
2. Linkage only detectable in closely linked markers
What happens when you have more generations?
You get smaller blocks and more cross overs occur
- the more the cross over the smaller the blocks
- linkages are not as strong
What does 50/50 linkage mean?
Independent sorting
- start its own linkage group
What happens if natural population was being used?
- Last common ancestor many generations ago
- Very small haplotype blocks
- Makes it harder to use because the get smaller and smaller
Genome wide associations
Look at many markers across genome and find co-segregation
What is Beta-thalassemia?
Fetal hemoglobin
Anemia
Insufficient amounts of healthy RBC
What is hemoglobins main function?
Transports oxygen throughout the body in mammals
What is hemoglobin altered by?
Deficiencies in iron and vitamin B12
- doesnt allow proper development of RBC becasue the proper precursors are not there
What is an example of genetic anemia?
Sickle cell disease
- is effected by mutated hemoglobin
Sickle cell disease is caused by what mutation?
Mutation in the beta globin gene
