I have data of a de novo mutation (in heterozygosity) in a patient which, obviously, is not present in her parents. I'm wondering how would I be able to identify in which parental lineage has the mutated allele come from.
I first thought of screening intronic regions flanking the exon where the mutation is, but that did not reveal anything in this case.
What other approaches would be useful in revealing the origin of this mutation?
using the method used by wilkie et al Nature Genetics 13(1):48-53 · June 1996
they looked up snps close to the mutation and designed ARMS primers to amplify from the different alleles separately to a point past the mutation. then amplified the samples and sequenced. if the maternal snp was AC and paternal was CC and the child was AC and the mutation sequenced to the amplimer from the A allele then the mutation is on the maternal chromosome. A number of snps might have to be analysed to find an informative snp
I guess it also depends how you found the mutation in the first place. If you've done exome sequencing, you could already check for heterozygous polymorphism which might be on the same read as your mutation.
Another option could be synthetic long reads followed by target exome capture. However, this is probably rather cost intensive (http://www.10xgenomics.com/applications/)
A third approach might be a long-range PCR around the locus of interest followed by sequencing using a technology which produces long reads (PacBio and/or Oxford Nanopores)
But all those are probably much more expensive than designing ARMS primers...
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