Simply put, the DNA double helix strand can be read in two directions commonly referred to as forward (plus)/top or reverse (minus)/bottom orientation. In terms of the nucleotides for that SNP, the pairing of A with T, and C with G, in the DNA double helix means that an A on the plus/top strand by definition is a T on the minus/bottom strand, and vice versa, and a C on the plus/top strand means a G on the minus/bottom strand (and vice versa). The majority of SNPs are ‘strand unambiguous’, such that combinations called on either strand are easily decipherable (e.g., A/G alleles on plus/top strand are T/C alleles on the minus/bottom strand). Ambigous flip issues arises when the possible combinations and their counterpart on the opposite strand are symmetrical across strands (A/T and C/G). It is now difficult to ascertain what is the major allele and which minor if the orientation of the read is not specified, especially if the major allele changes depending on the population you are referring too. See https://www.snpedia.com/index.php/Ambiguous_flip and https://www.snpedia.com/index.php/Orientation for more information.
Articles in this section
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