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US 11,610,646 B2Granted
Methods, systems and processes of identifying genetic variation in highly similar genes
AssigneeInvitae Corporation
InventorsDaniel J. Kvitek, Erik Gafni
Life of this patent
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Abstract
Provided herein are novel methods, systems and processes for mapping sequence reads to a modified reference genome and determining the presence or absence of a genetic variation, or the likelihood thereof, in a gene of interest in a subject.
Claims20
A computer-implemented method for determining a likelihood of a presence or absence of a genetic variation in a gene of interest for a subject, the method comprising:
- (a) providing a reference genome comprising (i) the gene of interest and (ii) a counterpart gene to the gene of interest, wherein at least one exon of the counterpart gene and the gene of interest are 70% to 99% identical;
- (b) substituting at least 30% of nucleotides in the at least one exon of the counterpart gene of the reference genome with an ambiguous nucleotide marker, thereby providing a modified reference genome;
- (c) mapping sequence reads obtained from a diploid subject to the modified reference genome, wherein (i) the subject comprises the gene of interest and the at least one exon of the counterpart gene, (ii) the sequence reads are obtained using a massively parallel sequencing method, and (iii) the sequence reads derived from the at least one exon of the counterpart gene of the subject map to the at least one exon of the gene of interest of the modified reference genome and not to the at least one exon of the counterpart gene of the modified reference genome;
- and
- (d) determining the likelihood of a presence or absence of a genetic variation in the gene of interest for the subject according to the sequence reads mapped to the modified reference genome.
2 more elements
A computer-implemented method for determining a likelihood of a presence or absence of a genetic variation in a gene of interest for a subject the method comprising:
- (a) providing a reference genome comprising (i) the gene of interest and (ii) a counterpart gene to the gene of interest, wherein the gene of interest is selected from the group consisting of PMS2, HBA1, HBG1, HBB, and SBSD and the counterpart gene to the gene of interest is selected from PMS2CL, HBA2, HBG2, HBD and SBDSP1, respectively;
- (b) substituting at least 30% of nucleotides in at least one exon of the counterpart gene of the reference genome with an ambiguous nucleotide marker, thereby providing a modified reference genome;
- (c) mapping sequence reads obtained from a diploid subject to the modified reference genome, wherein (i) the subject comprises the gene of interest and the at least one exon of the counterpart gene, (ii) the sequence reads are obtained using a massively parallel sequencing method, and (iii) the sequence reads derived from the at least one exon of the counterpart gene of the subject map to the at least one exon of the gene of interest of the modified reference genome and not to the at least one exon of the counterpart gene of the modified reference genome;
- and
- (d) determining the likelihood of the presence or absence of a genetic variation in the gene of interest for the subject according to the sequence reads mapped to the modified reference genome.
2 more elements
Dependencies are inferred from the claim text.