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I would like to know, except a familial study, is there another way to determine if a mutation/variation is cis or trans (i.e. on the same or different alleles)? For example by sequencing technique or other molecular biology procedure.

CIS               TRANS

+  +              +  +
|  |              |  |
A  |              A  |
|  |              |  |
B  |              |  B
|  |              |  |
+  +              +  +

Thanks

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Yes, it can be determined by sequencing but the sequencing read has to be long enough to span both the mutations. PacBio sequencing allows long reads but it also has higher error rate than the short read sequencing platforms like Illumina. If you know the gene locus then you can amplify the region using PCR and use Sanger sequencing too (for this the amplicon has to be cloned in a plasmid, transformed into bacteria and then single colonies must be sequenced; see Why does one combine PCR and cloning as ways for amplification of sequences?).

Another possibility is to look at the RNAs from this gene. If the two alleles have different expression then comparing the number of reads for each mutation might tell if they occur together. However, as I said it already depends on the two conditions: expression and dissimilar expression.

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  • $\begingroup$ Thanks for your reply. So, the family study seems to be the easiest and the cheaper method if both mutation are far away. $\endgroup$ – dridk Jun 5 at 15:42
  • $\begingroup$ @dridk There are some problems with family study: the two mutations may not have linkage and can segregate during crossover. Also, if you want to know about the current generation you might have to wait for them to have offspring. You need data for all of the family members. Moreover, if you don't have a very distinct trait associated with the different mutations then you would again have to rely on sequencing; so back to square one. $\endgroup$ – WYSIWYG Jun 5 at 16:42

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