Methods for determining carrier status
AssigneeGood Start Genetics, Inc.
InventorsEric D. Boyden, Gregory Porreca, Mark Umbarger
Life of this patent
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Abstract
The invention generally relates to methods for determining carrier status with respect to a condition or disease. In certain embodiments, the method involves exposing a sample to a plurality of molecular inversion probes capable of capturing DNA from at least one genomic region suspected of having an altered copy number and at least one internal control DNA known or suspected to have a stable copy number, capturing and sequencing DNA that binds to the molecular inversion probes, and determining a copy number state of the at least one genomic region based on the sequence results.
Claims17
A method for determining copy number, the method comprising:
- obtaining a sample from a patient, the sample comprising genomic DNA that includes a genomic region suspected of having an altered copy number and an internal control DNA having a stable copy number;
- fragmenting the genomic DNA to yield target nucleic acid comprising fragments of the genomic region and fragments of the internal control DNA;
- providing a plurality of molecular inversion probes capable of capturing the fragments of the genomic region and the fragments of the internal control DNA;
- exposing the target nucleic acid to the plurality of molecular inversion probes;
- capturing DNA that binds said molecular inversion probes;
- sequencing the captured DNA to produce target sequence reads and control sequence reads;
- enumerating target read counts from the target sequence reads and control read counts from the control sequence reads;
- normalizing the target read counts with respect to the control read counts;
- comparing the normalized target read counts to normalized read counts for a control diploid locus;
- and
- determining a copy number state of the genomic region;
- wherein one or more of the enumerating, normalizing, comparing, and determining steps is performed using a computer system comprising a processor couple to a memory.
A method of determining copy number between two paralogous genes, the method comprising the steps of:
- obtaining a sample from a patient, the sample comprising genomic DNA that includes a first gene, a second gene, and an internal control genetic locus, wherein the first gene and the second gene are paralogs;
- fragmenting the genomic DNA to yield target nucleic acid comprising fragments of the first gene, the second gene, and the internal control genetic locus;
- providing a plurality of molecular inversion probes capable of capturing the fragments of the first gene, the second gene, and the internal control genetic locus;
- exposing the target nucleic acid to the plurality of molecular inversion probes;
- capturing DNA that hybridizes to one or more of the plurality of molecular inversion probes;
- sequencing the DNA;
- enumerating read counts from the sequenced DNA;
- normalizing the read counts for each of the first gene and the second gene with respect to the internal control genetic locus;
- comparing normalized read counts for each of the first gene and the second gene to normalized read counts for a control sample with a known number of copies of the first gene and the second gene;
- and
- determining relative copy number of the first gene and the second gene based upon the comparing step;
- wherein one or more of the enumerating, normalizing, comparing, and determining steps is performed using a computer system comprising a processor couple to a memory.
Dependencies are inferred from the claim text.