Chromosomal rearrangements are frequently monitored by fluorescence in situ hybridization (FISH) using large, recombinant DNA probes consisting of contiguous genomic intervals that are often distant from disease loci. The Company has developed smaller, targeted, single-copy probes directly from the human genome sequence. The primary applications are in congenital disease and cancer diagnosis, but there are other emerging applications for which these probes are well suited (stem cell characterization, for example). These probes detect much smaller abnormalities than conventional FISH probes, delineate chromosome abnormality breakpoints, and can be targeted to specific regions within genes.
Probe sets have been designed genome-wide using our patented abinitio_probesTM. In addition to FISH, the company has designed oligonucleotide microarrays for array comparative genomic hybridization and solution capture arrays for targeted sequence enrichment prior to next generation sequencing. The aCGH arrays give more reproducible results than other commercial products. The capture arrays are designed for very high density coverage of inter- and intra-genic sequences, including non-repetitive sequences that other sequence enrichment products avoid including. This produces better coverage for discovery of novel variants.
The company produces both standard and custom genomic probes from computationally defined, single-copy genomic sequences. Single-copy FISH (SC-FISH) probes are produced directly from genomic DNA, and thus more quickly than by recombinant DNA techniques. Probe sequences are inferred from DNA sequences of larger genomic intervals with software that determines the locations of repetitive DNA elements contained in these sequences. The probes are 2-kb to 10-kb in length , synthesized in vitro, purified, and detected by FISH to chromosomes. The SC-FISH probes are then hybridized individually or in combination to human chromosomes.
Hybridization results are analogous to conventional FISH, except that these shorter probes can also be readily visualized. By contrast with conventional FISH, pre-annealing or blocking with unlabeled, repetitive DNA is unnecessary, as scFISH probes lack these sequences. Combinations of probes from the same region can be designed to give single or multiple hybridization signals on metaphase chromosomes.
The Company has developed SC FISH probes from many human chromosomal regions. More than 200,000 such probes have been predesigned, covering most anticipated diagnostic applications. In addition, over 500 SC FISH probes have already been qualified on metaphase spreads. This streamlined approach to the development and production of single-copy, sequence-specific hybridization products is the key advantage of SC Technology.