As you known, there have been lots of articles discussing "Association study design" and "Linkage analysis study design". What about "exon-sequencing project design"?
1. the sample collection principle
2. the sample size
3. whether it is suitale to choose exon-sequencing or some other technology
4. and some other attention.
What in particular are you interested in? The design completely depends on the outcomes you are looking for. is it in relation to using WES to look for rare mutations in a patient cohort? or are you using the technology for more population based outcomes?
It seem that whole exon sequencing was used to discover rare mutation? then how many sample size are needec usually?
Again it depends on the cohort, are you expecting the inheritance pattern to be recessive or de novo/dominant? Do you have more than one affected patient with the same disorder? or is it restricted to one pedigree? Do you have the luxury of appropriate patient material for follow up confirmatory studies.
I think exome sequencing projects are most successful when they are coupled with key features that allow powerful filtering to eliminate the vast majority of benign DNA variations that will be detected:
1) A moderate to large family with the disease that will allow linkage studies to exclude the majority of the DNA variations from considerations (i.e. 97% of the genome).
2) A highly consanguineous family that has a likely recessive, likely identity by descent homozygous mutation that will facilitate homozygosity mapping.
Such unique cases help with the daunting task of eliminating false positives - finding the disease-causing mutation in the midst of countless benign variants.
Good luck
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