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Is it recommended to joint genotype samples in a mutation accumulation experiment?

Hi,

I have a general usage question. I am analyzing whole-genome sequence data from a yeast mutation accumulation experiment. The experimental design is as follows:

1 ancestor
48 "progenitor" lines (initially genetically identical to the ancestor)
~2000 generations of MA
Whole-genome short-read Illumina sequencing of 48 progenitors + ancestor

My main goals are to 1. determine mutation rate, 2. determine types of mutations (SNPs vs indels, transitions vs transversions, etc) and 3. find any aneuploidy, if present.

In previous experiments, my lab has used UnifiedGenotyper and found variants on all samples individually, then combined them together (using CombineVariants).

I see that GATK is now recommending using joint genotyping, and I am wondering if that is recommended for this sort of experiment?

I need to ensure that the only variants in my "progenitor" samples are from the progenitors themselves, and not also in the ancestor. It seems to me that joint genotyping and base recalibration is a good way to go about this, but I wanted to get a second opinion.

Many thanks in advance!

-Holly

Answers

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