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The mammalian cell line CHO-K1 has 24,383 genes. After 70 doublings (from a starting number of cells, 1) a total of ~4,000 mutations have occurred in the overall population of cells (i.e. not all in one cell), due to incorrect DNA breakage repairs (non-homologous end joining), with the mutations randomly distributed throughout the genome. Assuming that 2% of CHO genome consists of crucial genetic information (1.5% coding and 0.5% regulatory). What number of genes will be affected by these mutations?

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I was thinking that the mutations should be spread randomly and so 24383*70/4000 genes may be affected but doesn't that assume the mutations are one per gene and the affected areas are actually important to protein expression?

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  • $\begingroup$ 70 doublings from starting number of cells = ? $\endgroup$
    – hello_there_andy
    Mar 11, 2017 at 9:15
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    $\begingroup$ starting number of cells = 1 $\endgroup$
    – JFOXX
    Mar 11, 2017 at 9:16

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I suspect this question is a lot easier than it makes itself out to be, though I may not be thinking straight. It doesn't matter how many cells you start with or how many doublings there are. Nor, for that matter, does it matter how many genes each cell has. There's a 2% chance that a random mutation will affect "crucial genetic information"; I must assume that that refers to genes. So $0.02*4000=80$ mutations would be expected to affect genes.

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    $\begingroup$ Just to be picky: the concept of gene is always a bit fuzzy and many regulatory regions being so far from the coding regions that many would not consider most regulatory sequences as being part of genes. However, introns which are in the other 98% category would quite definitely be considered part of a gene. $\endgroup$
    – Remi.b
    Mar 8, 2017 at 6:58
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    $\begingroup$ @Remi.b Agreed, though in that case there doesn't seem to be enough information to answer the question. Or perhaps they are expected to just use the 1.5% value for CDS. $\endgroup$
    – canadianer
    Mar 8, 2017 at 7:06
  • $\begingroup$ Some definitions of a gene: en.wikipedia.org/wiki/Gene, but it would be better to follow convention: ensembl.org/info/website/glossary.html, or if that does not engage sufficiently then perhaps some video tutorials? vectorbase.org/tutorials/… $\endgroup$
    – hello_there_andy
    Mar 11, 2017 at 9:18

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