Breakpoint resolution for copy number variation analysis

Question

I am reading [1].

One limitation of the Read Depth approach is that "the breakpoint resolution is often poor". Which is the meaning of low-resolution breakpoint in this case?

Breakpoint is defined as the sequence breakpoint:

Examples of a structural variation include a large deletion, insertion, duplication and inversion. Each requires the DNA duplex to be broken and rejoined, and this creates a new sequence of bases at the rejoined sites, i.e. the breakpoints.

Sequencing the new breakpoint regions is a good way (perhaps the only way?) to demonstrate an inversion, which does not increase or decrease the amount of DNA.

Original sequence: 123456789

Sequence with inversion: 123765489

Breakpoint sequences are at 37 and 48

[1]: C. Alkan, B. P. Coe, and E. E. Eichler, “Genome structural variation discovery and genotyping,” Nature Publishing Group, vol. 12, no. 5, pp. 363–375, Mar. 2011.

Answer 1

It means that it is hard to tell the precise location on the chromosome where the structural variation event starts and finishes using only read-depth information.

Read depth is measured by counting the number of mapped reads that overlap targeted regions aka bins. These bins are typically many basepairs wide and are used to normalize coverage with respect to various parameters (e.g. GC content). Smaller bins can give better breakpoint resolution but have noisier statistics. Large bins have better statistics but can't be used to precisely call the SV boundaries.

The CNVnator paper discusses the topic https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106330/