jhrf
commented
5 years ago Hi Adamtaranto,
Thanks for the query.
Telomerecat does not consider the reference at all when deciding whether a read is subtelomeric (as a result it works on non-human samples that have a TTAGGG TERC sequence). This is handy because the literature suggests that subtelomere regions are a changeable region of the genome. Telomerecat works on the assumption that "real telomere" is comprised of sequence that matches the canonic repeat 90% of the time. We then do some error calling to bring down false positive.
Thus, the scenario you describe above where de novo gain of telomere occurs would, I believe, manifest in a lengthening of telomere as reported by telomerecat.
As long as the new regions were truly telomeric (i.e found on the end of the chromosome) then they would not be considered interstitial telomere regions (ITR).
Does this clarify things?
How would telomerecat handle cases where a broken chromosome is stabilised by the de novo gain of telomeres? Reads from newly formed 'sub-telomeric' regions ought to map within the original reference chromosome, but their telomeric mates would not map concordantly to the reference. Do you count unmapped reads towards the total telomere space?
Also, in this case, would the two new telomeres be excluded from the total telomere count as ITR's? I imagine this would artificially increase the telomere length estimate.