METHODS FOR MONITORING THE EXPRESSION OF ALTERNATIVELY SPLICED GENES

1 . A method for determining the sequence of a variant splicing product of an initial mRNA transcript composed of exons and introns, the method comprising: employing different types of positive probes that hybridize with, and produce signals corresponding to, subsequences of the initial mRNA transcript in a sample solution; employing at least one type of negative control probe corresponding to each type of positive probe to produce negative-control-probe signals; detecting signals produced from positive probes in order to determine subsequences of the initial mRNA transcript present in a sample solution and construct an initial sequence of the variant splicing product; and detecting signals produced from the negative control probes to resolve ambiguities in the initial sequence of the variant splicing product.

2 . The method of claim 1 wherein the different types of positive probes include: positive tiling probes complementary to subsequences that span the sequence of the initial mRNA transcript; positive exonic tiling probes complementary to exon sequences within the initial mRNA transcript; and positive jump probes, each jump probe complementary to a subsequence including a potential splice point between two exons of the initial mRNA transcript.

3 . The method of claim 1 wherein negative control probes include: intron/exon-negative-control probes, including a subsequence that spans the junction between an exon and an intron in the initial mRNA transcript.

4 . The method of claim 3 further including: comparing a signal detected from an intron/exon-negative-control probe to the signal detected from a corresponding positive jump probe; when the signal detected from the intron/exon-negative-control probe is greater in signal strength to the signal detected from a corresponding positive jump probe, determining that an exon/exon splice point to which the positive jump probe is complementary is probably not present in the variant splicing product; when the signal detected from the intron/exon-negative-control probe is smaller in signal strength than the signal detected from a corresponding positive jump probe, determining that an exon/exon splice point to which the positive jump probe is complementary is probably present in the variant splicing product; and when the signal detected from the intron/exon-negative-control probe is comparable in signal strength to the signal detected from a corresponding positive jump probe, determining that the signal detected from the corresponding positive jump probe was generated by one of: non-specific association of the corresponding positive jump probe with non-fully-complementary target molecules; non-specific association of the corresponding positive jump probe with non-complementary target molecules; experimental error; instrumental error; and contamination.

5 . The method of claim 1 wherein the positive probes and negative control probes are bound to the surface of a microarray, and wherein signals are detected by scanning the microarray.

6 . Computer instructions that implement the method for determining the sequence of a variant splicing product of an initial mRNA transcript composed of exons and introns encoded in a computer readable data-storage medium.

7 . A microarray manufactured for use in identifying variant splicing products of an initial mRNA transcript, the microarray comprising: a substrate; and an active surface of the substrate onto which features containing probe molecules are deposited, the probe molecules including: positive probes complementary to expected subsequences of variant splicing products of the initial mRNA transcript; and two or more different types of negative control probes.

8 . The microarray of claim 7 wherein positive probes include: positive tiling probes complementary to subsequences that span the sequence of the initial mRNA transcript; positive exonic tiling probes complementary to exon sequences within the initial mRNA transcript; and positive jump probes, each jump probe complementary to a subsequence including a potential splice point between two exons of the initial mRNA transcript.

9 . The microarray of claim 7 wherein negative control probes include: intron/exon-negative-control probes, including a subsequence that spans the junction between an exon and an intron in the initial mRNA transcript.