Copy number analysis of genetic locus

摘要

Systems and methods for analyzing copy number of a target locus, detecting a disease associated with abnormal copy number of a target gene or a carrier thereof.

主权项

1. A system for analyzing copy number for a target locus comprising:
(a) a plurality of biological specimens, each individual biological specimen comprising: (i) a target locus; and (ii) one or more reference loci, wherein each of the reference loci comprise a known copy number; (b) one or more reagents for amplifying the target locus and the one or more reference loci from the plurality of biological specimens in parallel in a plurality of real-time PCR biological assays to generate detectable signals, such that the level of detectable signals for the target locus and the one or more reference loci correlate with their respective copy numbers; and (c) a computer readable medium having computer readable instructions recorded thereon for implementing a method on a computer, said method comprising: calculating
(i) a calibrator based on the determination of the copy number for the target locus and the one or more reference loci for the plurality of biological assays,wherein the calibrator reflects the overall background difference between the target locus and the one or more reference loci across the plurality of biological assays;(ii) a copy number estimate for the target locus for each of the plurality of biological assays normalized using the calibrator;(iii) a copy number call based on copy number estimates from replicated asssays for each of the plurality of biological specimens; and(iv) the quality of the copy number estimates and/or the statistical confidence of the copy number call for the target locus for each individual biological specimen.