Lecture 17

Question 1

What can cause DNA breaks

Answer 1

Can be spontaneous, just happens, or can be caused by an external factor like radiation
Both are fixed by repair mechanisms, cell intervention, but sometimes it can go wrong

Question 2

Chromosomal deletions and their causes

Answer 2

Just like it sounds, we get breaks in the DNA, usually double stranded breaks, and instead of ligating at the sites of breakage they skip over the broken out segment, resulting in the deletion
Another potential cause: crossing over between repetitive DNA, this is an issue becasue instead of pairing with their homologous chromosome to fix themselves via HR, they pair with themselves, resulting in a sort of cropping out of the segment
Refer to slide 5

Question 3

Williams syndrome deletion

Answer 3

Thought to be caused by a deletion of 17 genes (a cluster), this cluster of 17 genes is flanked by PMS regions, and sometimes in crossing over these sequences are confused with each other (so instead of PMS1 pairing with PMS2 it’ll pair with PMS2 of the homologous chromosome), leading to an uneven crossing over
This uneven crossing over gives one gamete with a lack of the cluster and one gamete with double cluster
Note: deletion in this case is complemented by a duplication on another, not always the case

Question 4

How can you detect chromosomal deletions

Answer 4

Observation of a karyotype (comparing the length or pairing of homologous chromosomes)
Genomic techniques like DNA sequencing can be used to analyze DNA
Complementation test

Question 5

How can complementation tests be used to test for chromosomal deletions (and a spin on that test)

Answer 5

You cross your unknown chromosome/DNA sample with a tester containing all recessive copies for visible genes
Any place the unknown DNA has a wild type gene, well see it in the offspring, and anywhere we dont have the restored dominant phenotype we know there is no wild type therefore no allele so a deletion
Not a totally sure thing, could just be recessive, but chances of both random unrelated organisms having teh same chromosomal mutation rendering it non-functional in the same way such that they cant complement each other may be less likely than a deletion
The opposite can also be done, using known deletions to map mutant alleles

Question 6

What do we call large duplications

Answer 6

Segmental duplications

Question 7

Inversions

Answer 7

Another type of chromosomal rearrangement, a sequence is accidentally chopped out and reinserted in the correct spot but in the wrong orientation
Two types of inversions: paracentric: does not include the centromere and pericentric, does include the centromere

Question 8

What are the somatic consequences of chromosomal inversions

Answer 8

Effect depends on where the break point occurs
If the break does not occur in a gene, does not separate the promoter from its gene and does not affect its regulation, no big
If the break point is within 1 gene that’s obviously an issue you’re separating it in two
Breaking point between 2 genes its arguably worse because now we have a gene fusion, 2 are likely defective now