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  • Why is Chromosome 19 unreliable?

    Hi there,

    I'm doing low-coverage CNV-seq on illumine HiSeq 2500. I've been told that chromosome 19 is not trustworthy but am really struggling to find out why? Can anyone explain or throw me a reference I can read on this?

    Many thanks

  • #2
    What kind of "not trustworthiness" are you referring to? It does appear that Chr19 has the highest number of alternate reference loci: http://www.ncbi.nlm.nih.gov/projects...urrent-regions

    Issues with chromosome 19: http://www.ncbi.nlm.nih.gov/projects...filters=chr:19

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    • #3
      Chromosome 19

      Many thanks for your reply.

      Well I was told that when analysing my data not to trust gains/losses that are in centromeric/telomeric regions (CNAs are overrepresented here) and to ignore Chr 19 as apparently these are not reliable. Is that a reflection of this high incidence of alternate reference loci you mentioned? Also why is this the case - is it a particularly repetitive chromosome?

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      • #4
        I have just been reading a comparative genomics paper, and apparently human chr 19 is particularly 'gene rich'.

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        • #5
          centromeric/telomeric regions tend to be highly repetitive regions which is why you might run into overrepresentation of CNAs. 19 does have a very high gene:bp length ratio ("gene rich") but I don't know why that would make it unreliable for CNAs?

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          • #6
            I think the high number of alternate reference loci is a fairly plausible explanation. Looking at all the alternatives, for chr19, in total, they add up to about a quarter of the length of the chromosome. By comparison, for chr18 is is 0.7% and for chr20 it is 2%. It's not quite as simple as that, but it does suggest that there are a lot of different ways of arranging chr19. If you are doing copy number and using a pooled control sample - i.e. not the same person as the normal, there could be quite a difference in how well your test and control samples align to the main chr19 reference, which will make the apparent copy number of chr19 quite variable from person to person.

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