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More often than not, we expect that the reference genome will include the most common allele, which is also likely to be the ancestral allele. Thus, if C->T mutations are more common than T->C mutations, we expect to see an imbalance of C->T versus T->C changes. Further, when comparing rare and common variants, we expect the imbalance to be stronger for lower frequency variants.
 
More often than not, we expect that the reference genome will include the most common allele, which is also likely to be the ancestral allele. Thus, if C->T mutations are more common than T->C mutations, we expect to see an imbalance of C->T versus T->C changes. Further, when comparing rare and common variants, we expect the imbalance to be stronger for lower frequency variants.
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