Screening for common variants in Cystic Fibrosis

Question

[kdc15]

Hi,

I am trying to design a study (as part of an assignment) to detect a novel variant in Cystic Fibrosis. It is based on finding this in one patient (a newborn) and I am expected to carry this out in 3 steps:

1. screening out any common variants
2. detecting any novel variant/s
3. Testing the functional effect of that variant.

I am having trouble deciding what is the best method to use to screen out common variants. I was thinking of using SNP arrays, but have now been advised that this is more useful in common diseases. I am now confused.

Please help!

[WouterDeCoster]

Shouldn't you take into account that the disease is recessive? You could use ExAC for task 1, and eliminate all variants with a (homozygous) population frequency above a certain threshold.

[kdc15]

Hi,

Thank you for replying. I am actually a Master's student nearly two months into my course. I have only just been exposed to omics technologies, so my knowledge of databases and which technologies to use are limited. So do you recommend looking at databases (such as ExAC) to screen out common variants, rather than a PCR based method such as MLPA?

My main problem at the moment is trying to understand why I need to use two different technologies to distinguish between common variants and novel variants. Surely by comparing to databases (or CFTR genes in non CF patients) I could filter out those common variants?

[WouterDeCoster]

Unless you are working on an isolated population, many variants can already be included based on the population frequency in huge databases such as ExAC. That will save you lot's of money because you don't have to start genotyping those variations yourself. You can still have population specific variants, but you already greatly reduce the number of candidate variants using databases.

[kdc15]

Thanks a lot. This is really helpful!