Analysis methods
View Patent ↗The invention generally relates to methods for analyzing nucleic acids to identify novel mutations associated with diseases. In certain embodiments, methods of the invention involve obtaining nucleic acid from a subject having a disease, identifying at least one mutation in the nucleic acid, and comparing the mutation to a database of mutations known to be associated with the disease, wherein mutations that do not match to the database are identified as novel mutations.
1. A method for identifying a novel mutation associated with a disease, the method comprising:
obtaining nucleic acid from a subject having a disease;
determining that the nucleic acid comprises a variant comprising an insertion or deletion;
comparing the variant to a database of variants known to be associated with the disease, wherein a variant that does not match to the database is identified as a novel variant;
determining a lower boundary and an upper boundary of an equivalent insertion/deletion region (EIR) of the novel variant;
determining that part of the EIR falls within a functional region.
2. The method according to claim 1 , wherein determining that the nucleic acid comprises a variant comprising an insertion or deletion comprises:
sequencing the nucleic acid; and
comparing the sequence of the nucleic acid to a reference sequence.
3. The method according to claim 2 , wherein sequencing is sequencing-by-synthesis.
4. The method according to claim 3 , wherein sequencing-by-synthesis is single molecule sequencing-by-synthesis.
5. The method according to claim 2 , wherein the reference sequence is a consensus human sequence or a sequence from a non-diseased sample.
6. The method according to claim 1 , wherein prior to determining that the nucleic acid comprises a variant comprising an insertion or deletion, the method further comprises attaching a barcode sequence to the nucleic acid.
7. The method according to claim 1 , wherein the disease is cystic fibrosis.
8. The method according to claim 7 , wherein the subject is Hispanic.
9. The method according to claim 1 , further comprising determining that the novel variant is causative of the disease by annotating the variant with functional information.
10. A method for determining if a mutation is causative of a disease, the method comprising:
conducting an assay to obtain a nucleic acid sequence from a subject having a disease;
determining a presence of at least one novel variant comprising an insertion or deletion in the sequence;
annotating the variant with appropriate functional information;
identifying a lower and upper boundary of an equivalent insertion/deletion region (EIR) of the novel variant; and
determining that part of the EIR falls within a functional region.