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  • how to deal with adjoining SNPs?

    Dear All,
    I'm dealing with some sequencing data coming from an Illumina platform and assembled on a reference genome. We employed standard filters to reduce gaps (and therefore false mismatches), but still I'm finding numerous adjoining SNPs in the dataset. I'm afraid these could be artifacts caused by reads assembly; people in bibliography present some contrasting opinions, sometimes considering these kind of SNPs as regular (and valuable) data, some other times getting rid of them.
    What I'd like to ask you is if anybody supports biological reasons at the base of adjoining SNPs formations ore else if there is any filtering tool devoted to this problem. I could brutally eliminate these SNPs from the dataset, but maybe somebody came up with a more elegant way .

  • #2
    You could have a mixture of real and artifactual MNPs - so a brute force filtering of them wouldn't be advisable.

    Are you seeing a read-position bias to the adjacent SNPs? If you are then these could be a symptom of declining base quality at the end of reads. If so read trimming would remove this artifact e.g. using the bwa aln -q option.
    Once the position bias is eliminated then you could have some real MNPs remaining (multi-nucleotide polymorphisms).

    We have found some of these ourselves (validated by Sanger sequencing):
    Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye malformations that cause a significant proportion of childhood visual impairments. Several disease genes have been identified but do not account for all MAC cases, suggesting that additional risk loci exist. We used singl …


    Also see Rosenfeld et al 2010
    Genomic sequence comparisons between individuals are usually restricted to the analysis of single nucleotide polymorphisms (SNPs). While the interrogation of SNPs is efficient, they are not the only form of divergence between genomes. In this report, we expand the scope of polymorphism detection by …


    These MNPs can cause problems for mutation annotation software as usually they report the adjacent mutations separately - rather than the combined effect of both mutations on the codon.

    Comment


    • #3
      Thank you pmcget for the kind reply. That are some really interesting clues, I'll work in that direction to untangle this knot.
      Cheers!

      Comment

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