Please use the link to answer the questions! https://www.nature.com/scitable/top
ID: 211779 • Letter: P
Question
Please use the link to answer the questions!
https://www.nature.com/scitable/topicpage/dna-deletion-and-duplication-and-the-associated-331
3. Explain why low copy repeat (LCR) sequences, like the pericentromeric regions of chromosomes, are often substrates for non-allelic homologous recombination (NAHR). When do such NAHR events lead to inversions and translocations?
4. You are a molecular geneticist. You are attempting to develop a cure for a genetic disorder that results from either a deletion or duplication. Which in your opinion would be the easier of the two conditions to treat? Explain your reasoning.
Explanation / Answer
A large number of DNA rearrangements of the same genomic interval have been observed in different individuals, that is they have a recurrent nature. Most recurrent genomic rearrangements are caused by NAHR between two low-copy repeats (LCRs, also called segmental duplications, SD). LCRs are region-specific DNA blocks usually of 10 to 300 kilobase (kb) in size and of > 95% to 97% similarity to each other.
Due to their high degree of sequence identity, non-allelic copies of LCRs, instead of the copies at the usual allelic positions, can sometimes be aligned in meiosis or mitosis. This so-called 'misalignment' and the subsequent crossover between them can result in genomic rearrangements in progeny cells. The non-allelic copies thus act as the mediators (that is, substrates) of the homologous recombination and they are responsible for the observed breakpoint clustering.
1. When the two LCRs are located on the same chromosome and in direct orientation, NAHR between them causes duplication and/or deletion.
2. When they are on the same chromosome but in opposite orientation, NAHR results in inversion of the fragment flanked by them.
3. NAHR between repeats on different chromosomes can lead to chromosomal translocation.
2. In my opinion the duplication condition would be easier to treat than the deletion condition because the phenotypes of the deletion are more severe than those caused by duplications