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US 2012/0059594 A1Published application
Compositions and methods for discovery of causative mutations in genetic disorders
AssigneePopulation Diagnostics, Inc.
InventorsEli Hatchwell, Peggy S. Eis
Life of this patent
Estimating the term…
Abstract
The compositions and methods provided herein allow for identification of causative genetic biomarkers for a disease condition or drug response.
Claims38
A method of determining a causative mutation of a disease or condition in one or more subjects affected by the disease or condition comprising:
- (a) screening the genome(s) of one or more subjects affected by the disease or condition with an assay to provide information on one or more copy number variants;
- (b) comparing via a computer, the information on the one or more copy number variants from the genome(s) of the one or more subjects to a compilation of data comprising frequencies of copy number variants in at least 100 subjects unaffected by the disease or condition, wherein said computer comprises computer executable logic that provides instructions for executing said comparison;
- (c) determining a statistical significance of the one or more copy number variants to a disease or condition associated with a genotype from the comparison of step (b), or determining whether the one or more copy number variants is present in the one or more subjects affected by the disease or condition but not present in the compilation of data from the comparison of step (b);
- (d) sequencing the one or more copy number variants or genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in one or more subjects affected by the disease or condition, to identify a first set of one or more genetic variants;
- (e) sequencing the one or more copy number variants or one or more genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in at least 100 subjects unaffected by the disease or condition, to identify a second set of one or more genetic variants;
- (f) determining a statistical significance of the first set of one or more genetic variants by comparing the sequencing information of step (d) to the sequencing information of step (e).
3 more elements
The method of claim 17, wherein the genome of the subject is screened only if the subject does not have a subset of causative mutations previously determined based on:
- (a) ascertainment of the frequency of occurrence of causative mutations in subjects affected and unaffected with the disease or condition;
- and/or
- (b) ascertainment of the pathogenicity of causative mutations in subjects affected with the disease or condition.
A method of identifying a pathogenic mutation of a disease or condition in one or more subjects affected by said disease or condition comprising:
- (a) providing one or more copy number variants associated with said disease or condition in said one or more subjects affected by said disease or condition;
- and
- (b) identifying said pathogenic mutation by sequencing said one or more copy number variants and a portion of the genetic material upstream and/or downstream of said copy number variant.
A computer readable medium comprising instructions for determining a causative mutation or a disease or condition in one or more subjects affected by the disease or condition, said instructions comprising the steps of:
- (a) screening the genome(s) of one or more subjects affected by the disease or condition with an assay to provide information on one or more copy number variants;
- (b) comparing via a computer, the information on the one or more copy number variants from the genome(s) of the one or more subjects to a compilation of data comprising frequencies of copy number variants in at least 100 subjects unaffected by the disease or condition, wherein said computer comprises computer executable logic that provides instructions for executing said comparison;
- (c) determining a statistical significance of the one or more copy number variants to a disease or condition associated with a genotype from the comparison of step (b), or determining whether the one or more copy number variants is present in the one or more subjects affected by the disease or condition but not present in the compilation of data from the comparison of step (b);
- (d) sequencing the one or more copy number variants or genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in one or more subjects affected by the disease or condition, to identify a first set of one or more genetic variants;
- (e) sequencing the one or more copy number variants or one or more genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in at least 100 subjects unaffected by the disease or condition, to identify a second set of one or more genetic variants;
- (f) determining a statistical significance of the first set of one or more genetic variants by comparing the sequencing information of step (d) to the sequencing information of step (e).
3 more elements
A computer system comprising instructions for determining a causative mutation or a disease or condition in one or more subjects affected by the disease or condition, said system comprising instructions for executing the steps of:
- (a) screening the genome(s) of one or more subjects affected by the disease or condition with an assay to provide information on one or more copy number variants;
- (b) comparing via a computer, the information on the one or more copy number variants from the genome(s) of the one or more subjects to a compilation of data comprising frequencies of copy number variants in at least 100 subjects unaffected by the disease or condition, wherein said computer comprises computer executable logic that provides instructions for executing said comparison;
- (c) determining a statistical significance of the one or more copy number variants to a disease or condition associated with a genotype from the comparison of step (b), or determining whether the one or more copy number variants is present in the one or more subjects affected by the disease or condition but not present in the compilation of data from the comparison of step (b);
- (d) sequencing the one or more copy number variants or genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in one or more subjects affected by the disease or condition, to identify a first set of one or more genetic variants;
- (e) sequencing the one or more copy number variants or one or more genome regions encompassing the one or more copy number variants determined to be statistically significant or present in the genomes of one or more subjects affected by the disease or condition but absent or present at lower frequency in subjects unaffected by the disease or condition according to step (c), in at least 100 subjects unaffected by the disease or condition, to identify a second set of one or more genetic variants;
- (f) determining a statistical significance of the first set of one or more genetic variants by comparing the sequencing information of step (d) to the sequencing information of step (e).
3 more elements
Dependencies are inferred from the claim text.