Method for quantifying abundances of biomolecule variants

C - Chemistry – Metallurgy – 12 – Q

Patent

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C12Q 1/68 (2006.01) C40B 30/04 (2006.01) G01N 33/50 (2006.01) G01N 33/68 (2006.01)

Patent

CA 2531997

The invention is a method for the rapid and high-throughput quantitative determination of abundances of biomolecule variants in biological samples, which may be derived from a normal-physiological or pathological state, or derived from experimentally- manipulated systems. Biomolecule variants that can be quantified using the method include mRNA splice isoforms (e.g, generated by alternative splicing), nucleic acid or protein variants generated by base or amino acid sequence modifications respectively, or variants generated by the processes of DNA recombination, single base substitution (e.g. resulting from mutations or single nucleotide polymorphisms), or larger alterations such as deletions and copy number variations. The method uses information derived from a biomolecule profiling device, such as a DNA or protein microarray that contains multiple biosensor probes (e.g. oligonucleotides or antibodies) for detection. At least one of the probes associated with the device detects at least two variants per common precursor biomolecule. The method can be applied to generate "signatures" representing abundances of multiple biomolecule variants in one or more conditions. These signatures have significant utility in pharmacogenomics applications including disease diagnostics as well as predictions of disease susceptibility, drug toxicity and efficacy. The method also has wide utility in basic biomedical research as a tool for the advancement of knowledge of the global properties of gene expression associated with biomolecule variant expression associated with living and viral systems.

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