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Clarification on comments re GeneticVariation

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CLOSED - Need clarification on comments re GeneticVariation (row 29)

Current Definition

DEFINITION: The difference(s) in the nucleotide sequence of a biologic entity relative to a reference sequence.

EXAMPLE(S): A single nucleotide change from adenosine to cytosine, of the CAG trinucleotides repeats in the Huntington gene.



Ballot Comment

genetic reference supports nucleotide and amino acid changes, while the variant only supports nucleotide change. Also examples are not accurate.

Proposed Definition

DEFINITION: The observed sequence relative to the genetic reference sequence.

EXAMPLE(S): TT (nucleotide example) L(amino acid change example)



Current Disposition

Pending Input From Submitter

Proposed Disposition Comment

Need clarification and coordination with LSDAM SMEs to ensure their intended semantic is accurately represented.

Not clear if this is referencing the GeneticReference class (with which there is no direct association in the model) or if it's a more general use of the term "genetic reference" since this seems to be a comment on the class GeneticVariation. Is this saying GeneticVariation should only be about nucleotide change? If so should there be an amino acid change example? Also the proposed definition change seems to include observed sequences that are NOT variations since it leaves out the term "difference(s)" - is that too broad given the class name?

Outstanding Questions

  • Is the proposed definition a fundamental change or expansion of the original concept?
  • If so, is this consistent with the LSDAM SMEs intention? (Perhaps GeneticVeriation as defined was just one example of a subclass of a NucleicAcidSequenceFeature.)
  • Should we expand the definition or add another subclass instead?
  • Should there be a connection between the GeneticVariation class and the GeneticReference class? And if so, what's the nature of the relationship?
  • Is this clarifying what's in the model now (in scope for this ballot reconciliation) or adding new semantics (out of scope for this reconciliation effort)?


Lauren Becnel: I think in the LS DAM the concept of variation in genes, mRNAs, proteins were separate. Here, the new definition seeks to broaden in to molecular variation, not genetic variation. This fits broadly into the question of scope here – is it limited to CG or to clinical ‘omics? When that is answered, I can better give input as to whether the original or proposed definition is more appropriate.

Q from WENDY (TYPE: DISCUSS): Scope is a good question - do we need advice from steering committee???

DISCUSSION 20160225: if there are lots of other molecular variations, where does this concept fit in the broader concept? If we are looking at specifically genetic variation, shouldn’t we look at modeling by reference to another more domain-specific model? The proposed definitions and example are OK.

Lauren will provide some additional real-world examples related to some of our other examples.

Lauren Becnel, 20160226: "The BRCA1 gene can contain an insertion at position 5382, BRCA1 gene.c.5382insC, or a single nucleotide polymorphism, at position 61 converting a to a G, 61C->G."


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