Abstract: Methods of detecting a candidate genetic anomaly such as a candidate duplication in a genome are disclosed. The methods comprise quantifying fluorogenic assays for alleles of a genetic locus from a plurality of individual genomes, identifying ranges of fluorescent intensities indicative of individual genomes homozygous for a first allele, homozygous for a second allele, or heterozygous for both alleles, and identifying individual genomes in which the fluorescence intensities are outside the range of intensities indicative of homozygosity or heterozygosity for the genetic locus.

Abstract: Disclosed is a method for determining the number of repeat units in a repeat region of a target nucleic acid. In a first aspect, the method of the invention includes the steps of annealing a primer to a target nucleic acid; performing a first primer extension reaction using a first primer extension reagent; separating the target-primer hybrid and unreacted first primer extension reagent; performing a second primer extension reaction using a second primer extension reagent, wherein at least one of the first or second primer extension reagents includes an extendible nucleotide having a label attached thereto; separating the target-primer hybrid from unreacted second primer extension reagent; measuring a signal produced by the label; treating the label so as to render the label undetectable; and repeating the above steps until the signal is substantially less than a signal detected in a previous cycle.

Abstract: Methods for amplifying polynucleotides, e.g., by PCR, in a sample comprising polynucleotide targets present at very low concentration, comprising: (a) applying amplification reactants to the surface of a substrate comprising reaction spots, wherein the reactants comprise the sample and an amplification reagent; (b) forming a sealed reaction chamber, having a volume less than about 120 nanoliters, preferably less than about 20 nanoliters, over each of said reaction spots; and (c) thermal cycling the substrate and reactants. In one embodiment, the forming step comprises loading a sealing fluid, e.g., mineral oil, on the surface so as to cover the reaction spots. The present invention also provides microplates, comprising: (a) a substrate having at least about 10,000 reaction spots, each comprising a primer and a droplet of reagent having a volume less than about 120 nanoliters, preferably less then about 20 nanoliters; and (b) a sealing liquid isolating each of the spots.

Abstract: The invention relates to insulating combinatorial nucleobase oligomers that comprise universal base analogs, where the oligomers are formed by the ligation of two or more oligomer “blocks” via a covalent linkage. Universal bases may serve to insulate specifically binding nucleobases from the effects of the covalent linker region joining two oligomer blocks together, so that the universal bases at least partially negate the Tm penalty caused by the covalent linkage, effective to reduce the required minimal length of the oligomer blocks and the combinatorial oligomer. The resulting insulating nucleobase combinatorial oligomers find use in any hybridization-based application, including use as probes and primers. The combinatorial oligomers of the present invention provide advantages over existing combinatorial oligomer systems currently known in the art.