Sample A: Cover Page of Thesis, Project, or Dissertation Proposal

demonstrate sub-optimal stability with the desired target [18, 54, 55]. One
such class is that of single nucleotide polymorphisms. For short
oligonucleotide probes (i.e. 25-mers) a single-base mismatch is supposed to
be sufficiently destabilizing that signal decreases markedly [9]. This is by no
means consistently observed, since there is a very large context dependence
[18, 55, 56]. In the equilibrium equations of duplex formation, the duplex
dissociation rate is slower than the single strand association rate, but
mismatches dissociate more rapidly than perfect matches; again, the
difference in rate constants is dependent on the type and context of the
sequence variant [28, 29].
c. Transcript Models. A second class of alternate alleles has to do with
transcript splicing. Gene models are routinely redefined as more evidence is
published [43], while probe designs are based upon a static definition of the
gene model at the manufacturing time. This means that probe annotation
must be continually updated by the investigator in order to understand which
probes should be deprecated and which should be selectively combined,
depending on the desired analysis. Unexpected outcomes are common,
including such observations as probes mapping to introns that thereby are
expected to have no signal, some of which have high responses, leading to
some doubt about the accuracy of the gene model [57].
d. Inaccessible Probes. As discussed above, any single-stranded nucleic acid
can form stable self complementary structures, due to intramolecular
hydrogen bonding and base stacking [22, 25, 54]. Such structures can
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