GENEMAP OF THE HUMAN GENES ASSOCIATED WITH LONGEVITY
First Claim
1. A method of constructing a longevity trait GeneMap in a human population, comprising screening for the expression level of or presence or absence of at least one allele of (i) at least one gene from Tables 4, 5 and 6 or (ii) at least one single nucleotide polymorphism (SNP) from Tables 2, 3 and 7 in at least one sample.
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Abstract
The present invention relates to the selection of a set of SNP markers for use in genome wide association studies based on linkage disequilibrium mapping. In particular, the invention relates to the fields of pharmacogenomics, diagnostics, patient therapy and the use of genetic haplotype information to predict an individual'"'"'s longevity, their protection against age-related diseases and/or their response to a particular drug or drugs.
42 Citations
148 Claims
- 1. A method of constructing a longevity trait GeneMap in a human population, comprising screening for the expression level of or presence or absence of at least one allele of (i) at least one gene from Tables 4, 5 and 6 or (ii) at least one single nucleotide polymorphism (SNP) from Tables 2, 3 and 7 in at least one sample.
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5-21. -21. (canceled)
- 22. A set of genetic markers comprising at least two SNPs of Tables 2, 3 and 7.
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26. A method for predicting the efficacy of a drug for treating an age-associated disorder in a human patient, comprising:
- a) obtaining a sample of cells from the patient;
b) obtaining (i) a gene expression profile or (ii) a set of genotype from the sample in the absence and presence of in vitro modulation of the cells with specific mediators;
the gene expression profile comprising one or more genes from Tables 4, 5 and 6;
the set of genotypes comprising one or more polymorphic loci from Tables 2, 3 and 7 and c) comparing the gene expression profile or the set of genotypes of the sample with a reference gene expression profile or a reference set of genotypes associated with efficacy of the drug, wherein similarity between the sample expression profile and the reference expression profile or between the set of genotypes and the reference set of genotypes predicts the efficacy of the drug for treating age-associated disorder in the patient. - View Dependent Claims (27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 132, 133, 134, 135, 136)
- a) obtaining a sample of cells from the patient;
- 37. A method for inducing a longevity-like state in a resident tissue or cell, comprising contacting the tissue or cell with at least one gene from Tables 4, 5 and 6 that induces a longevity-like state.
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40-43. -43. (canceled)
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44. A drug screening assay comprising:
- a) administering a test compound to an animal having an age-associated disorder, or related phenotype, or a cell composition isolated therefrom; and
b) comparing the level of gene expression of at least one gene from Tables 4, 5 and 6 in the presence of the test compound with one or both of the level of said gene expression in the absence of the test compound or in normal cells;
wherein test compounds which cause the level of expression of one or more genes from Tables 4, 5 and 6 to approach normal are candidates for drugs to treat age-associated disorders.
- a) administering a test compound to an animal having an age-associated disorder, or related phenotype, or a cell composition isolated therefrom; and
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45-46. -46. (canceled)
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47. A method for identifying a gene that regulates drug response in an age-associated disorder, comprising:
- a) obtaining a gene expression profile for at least one gene from Tables 4, 5 and 6 in a resident tissue cell induced for a longevity-like state in the presence of the candidate drug; and
b) comparing the expression profile of said gene to a reference expression profile for said gene in a cell induced for the longevity-like state in the absence of the candidate drug, wherein genes whose expression relative to the reference expression profile is altered by the drug may identifies the gene as a gene that regulates drug response in the longevity trait.
- a) obtaining a gene expression profile for at least one gene from Tables 4, 5 and 6 in a resident tissue cell induced for a longevity-like state in the presence of the candidate drug; and
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48. An expression profile indicative of the presence of longevity trait in a patient, comprising the level of expression of at least one gene of Tables 4, 5 and 6.
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49. A microarray comprising probes that hybridize to one or more genes of Tables 4, 5 and 6.
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50-51. -51. (canceled)
- 52. A method of diagnosing susceptibility to an age-associated disorder in an individual, comprising screening for an at-risk haplotype of at least one gene from Tables 4, 5 and 6, or comprising at least one SNP from Tables 2, 3 and 7, that is more frequently present in an individual susceptible to an age-associated disorder, compared to the frequency of its presence in a control individual, wherein the presence of the at-risk haplotype is indicative of a susceptibility to an age-associated disorder.
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59-95. -95. (canceled)
- 96. A method for determining the phenotype of a cell comprising detecting the differential expression, relative to a normal cell, of at least one gene from Tables 4, 5 and 6.
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100. A kit for assessing a patient'"'"'s risk of having or developing an age-associated disorder, comprising:
- a) detection means for detecting the differential expression, relative to a normal cell, of at least one gene shown in Tables 4, 5 and 6 or the gene product thereof; and
b) instructions for correlating the differential expression of said gene or gene product with a patient'"'"'s risk of having or developing an age-associated disorder. - View Dependent Claims (101)
- a) detection means for detecting the differential expression, relative to a normal cell, of at least one gene shown in Tables 4, 5 and 6 or the gene product thereof; and
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102. A kit for assessing a patient'"'"'s risk of having or developing an age-associated disorder, comprising:
- (a) at least one means for amplifying or detecting a sequence of at least one gene in Tables 4, 5 and 6, or at least one sequence comprising a SNP in Tables 2, 3 and 7, wherein the detection means includes nucleic acid probes or primers for detecting the presence or absence of an associated allele, a particular allele of a polymorphic locus, or the like or changes to at least one sequence of Tables 4, 5 and 6 or Tables 2, 3 and 7, and (b) instructions for correlating the presence or absence of at least one sequence of Tables 4, 5 and 6 or Tables 2, 3 and 7 with a patient'"'"'s risk of having age-associated disorder.
- View Dependent Claims (103)
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104. A method of assessing a patient'"'"'s risk of having or developing an age-associated disorder, comprising:
- a) determining the level of expression of at least one gene from Tables 4, 5 and 6 or gene products thereof, and comparing the level of expression to a normal cell; and
b) assessing a patient'"'"'s risk of having or developing an age-associated disorder, if any, by determining the correlation between the differential expression of said genes or gene products with known changes in expression of said genes measured in at least one parent suffering from an age-associated disorder.
- a) determining the level of expression of at least one gene from Tables 4, 5 and 6 or gene products thereof, and comparing the level of expression to a normal cell; and
- 105. A nucleic acid array comprising a solid support comprising nucleic acid probes which selectively hybridize to at least 5 different genes from Tables 4, 5 and 6 or at least 5 different SNPs of Tables 2, 3 and 7.
- 107. A method of diagnosing the longevity trait in a patient, comprising detecting a nucleic acid molecule encoding at least one protein from Tables 4, 5 and 6 in a fluid or tissue sample from the patient.
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112. (canceled)
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121-123. -123. (canceled)
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124. A method for diagnosing or prognosticating longevity comprising comparing the level of expression or activity of a polypeptide encoded by a gene of Tables 4, 5 and 6 in a test sample from a patient with the level of expression or activity of the same polypeptide in a control sample wherein a difference in the level of expression or activity between the test sample and control sample is indicative of the longevity trait.
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125-131. -131. (canceled)
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137-145. -145. (canceled)
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146. A kit for assessing a patient'"'"'s risk of having or developing an age-associated disorder, comprising:
- a) detection means for detecting the genotype of at least one polymorphic locus shown in Tables 2, 3 and 7; and
b) instructions for correlating the genotype of said at least one polymorphic locus with a patient'"'"'s risk of having or developing an age-associated disorder. - View Dependent Claims (147)
- a) detection means for detecting the genotype of at least one polymorphic locus shown in Tables 2, 3 and 7; and
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148. A method of assessing a patient'"'"'s risk of having or developing an age-associated disorder, comprising:
- a) selecting at least one polymorphic locus from Tables 2, 3 and 7;
b) determining a genotype for said at least one polymorphic locus from Table 1 in a patient;
c) comparing said genotype of b) to a genotype for said at least one polymorphic locus from Tables 2, 3 and 7 that is associated with the age-associated disorder; and
d) assessing the patient'"'"'s risk of having or developing the age-associated disorder, wherein said patient has a higher risk of having or developing the age-associated disorder if the genotype for said at least one polymorphic locus from Tables 2, 3 and 7 in said patient is the same as said genotype for said at least one polymorphic locus from Tables 2, 3 and 7 that is associated with the age-associated disorder.
- a) selecting at least one polymorphic locus from Tables 2, 3 and 7;
Specification