6
$\begingroup$

Generally variant calling programs (such as GATK-UnifiedGenotyper) look for differences between reference genome and submitted sequence. However, we all know that reference genome consist rare variants in various positions. If submitted sequence has this rare form of that variant, variant call doesn't see it and doesn't report at all. However, that variant could be very precious for analysis.

So, how can I solve this problem? What should I do to not miss that rare variants even they are in reference genome?

enter image description here

$\endgroup$
  • 2
    $\begingroup$ Please don't cross-post, as you did here: seqanswers.com/forums/showthread.php?t=50289 $\endgroup$ – Devon Ryan Feb 13 '15 at 23:25
  • 4
    $\begingroup$ Thanks for the answer. But Why shouldn't I? I want to reach people as many as possible. Actually I asked the same question on Quora. I don't think that it wrong. Seqanswers and Stackexchange are different platforms and may have different users. So, a user that is member of only single platform may miss my question. Cross-posting increase the possibility to get answer. $\endgroup$ – Can H. Feb 14 '15 at 8:42
  • 1
    $\begingroup$ Cross-posting is convenient for you, but doubles/triples/etc. the work expended by the community to help you. Why should people in a community B expend time helping you when those in community A have already provided you with the answer to your question? $\endgroup$ – Devon Ryan Feb 14 '15 at 9:22
  • 4
    $\begingroup$ Actually, I'll share the answer that I found in every platform that I asked question. So, everyone in both platform will learn the answer. More people will benefit. It's better right? $\endgroup$ – Can H. Feb 14 '15 at 10:25
1
$\begingroup$

If the reference sequence is associated with a disease or increased susceptibility to some phenotype, the the population you're using to compare against (with a variant) will show protection to it. So either way you're going to find an association, this will just change the sign of the coefficient.

$\endgroup$
1
$\begingroup$

Well, you'd hope that the "reference" sequence is of a healthy individual, and won't be carrying a highly detrimental allele that you care about.

Or get a bunch of control data from the 1K genome project, and compare them to the reference as well; they won't carry the rare alleles that your reference does.

$\endgroup$
0
$\begingroup$

The reference genome is a composite sequence from multiple individuals therefore scenario A should hardly occur, if at all. The unsatistying answer is that it is very unlikely that the rare variants of interest to you will be in the reference.

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.