The observed pattern of familial recurrence risk has long suggested that multiple variants are involved, but it has proven difficult to identify individual risk variants and little has been established about the genetic architecture underlying susceptibility.
Of note, there is extreme variation in the viral sequences from WEAU's transmitting partner RIER, which were sampled during chronic infection near the time of transmission to WEAU (Fig. 4A, grey branches); nevertheless, the variants found in WEAU, even at later time points, appear to have evolved from a single founder (Fig. 4A), a further indication that multiple variants were not transmitted.
Next, multiple variants were included into a single mixed model to investigate their joint effect.
The major ZP proteins showed high polymorphism because multiple variants are present with different molecular weights.
Tags with matches to multiple variants were attributed to the most common variant, so that each tag counted only once.
Sequences with multiple variants were minor: 0.362% exonic, 0.0599% intronic, and were excluded from the final dataset.
Mixed models on the sum of the effect alleles across multiple variants were again run in two steps.
The mSNP filter pipeline presented some unique challenges, because multiple variants were sought at a single position.
In all partial responders (P31, P21, P105; Fig. 2; Supporting Figs. 8, 9), multiple variants were present (3, 4, and 5 variants, respectively).
As the used PCR primers overlapped with part of the miRNA and miRNA* sequences, it is impossible to know whether multiple variants were present.
