Screening for structural variants
First Claim
1. A method of identifying a structural variant, the method comprising:
- exposing a nucleic acid in a sample to a plurality of molecular inversion probes (MIPs), each MIP comprising two targeting arms designed to hybridize upstream and downstream of a target in a reference genome;
connecting together two of the MIPs via arms that have hybridized to the same molecule of the nucleic acid by only one of the two targeting arms of each MIP to create an inter-probe product;
detecting the inter-probe product;
identifying a structural variant of the genome in the nucleic acid;
describing one or more breakpoints in the nucleic acid based on the two MIPs that each hybridizes to the nucleic acid by only one of its two targeting arms.
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Accused Products
Abstract
The invention relates to carrier screening and methods for describing a structural variant, such as a large rearrangement or chromosomal abnormality, in a person'"'"'s genome using probes that are designed to determine the person'"'"'s genetic sequence and reveal substitution mutations and small structural variants. Identifying a structural variant may include exposing a nucleic acid to a plurality of probes. Each probe has a linked pair of targeting arms designed to hybridize upstream and downstream of a target in a genome. The method includes hybridizing two of the probes to the nucleic acid and attaching the two probes together to create an inter-probe product as well as detecting the inter-probe product and reporting a structural variant of the genome in the nucleic acid.
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Citations
21 Claims
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1. A method of identifying a structural variant, the method comprising:
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exposing a nucleic acid in a sample to a plurality of molecular inversion probes (MIPs), each MIP comprising two targeting arms designed to hybridize upstream and downstream of a target in a reference genome; connecting together two of the MIPs via arms that have hybridized to the same molecule of the nucleic acid by only one of the two targeting arms of each MIP to create an inter-probe product; detecting the inter-probe product; identifying a structural variant of the genome in the nucleic acid; describing one or more breakpoints in the nucleic acid based on the two MIPs that each hybridizes to the nucleic acid by only one of its two targeting arms. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method of identifying a structural variant, the method comprising:
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exposing a nucleic acid from a patient to a plurality of probes, each probe comprising a linked pair of targeting arms comprising sequence designed to hybridize upstream and downstream of a target in a reference genome, wherein the plurality of probes are designed to cover at least a portion of a gene associated with a Mendelian recessive hereditary disorder; ligating together two of the probes that each hybridize to the nucleic acid by only one targeting arm to create an inter-probe product; circularizing at least some probes that hybridize to the nucleic acid by both targeting arms; sequencing the inter-probe product and at least a portion of the circularized probes to produce sequence reads; comparing the sequence reads to a reference genome; and describing one or more substitution mutations and a structural variant within the gene as found in the nucleic acid from the patient. - View Dependent Claims (16, 17, 18, 19, 20, 21)
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Specification