Single nucleotide polymorphisms diagnostic for schizophrenia
OwnerPaul S. Kaytes, Chi-Hse Tenginventors
Life of this patent
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Abstract
The invention provides nucleic acid segments of the human G protein coupled receptor Seq-40 gene including polymorphic sites. Allele specific primers and probes hybridizing to regions flanking these sites are also provided. The invention also provides methods for determining the genetic risk of developing schizophrenia or diagnosing schizophrenia.
Claims102
An isolated polynucleotide consisting of between 12 and 200 contiguous nucleotides of SEQ ID NO 1 or its complement including at least one Seq-40 polymorphic site selected from the group consisting of the polymorphic sites at positions 194, 601, 1029, 1038, 1074, 2106, 2185, 2359, 2663 and 2796.
An isolated polynucleotide comprising at least 12 contiguous nucleotides of SEQ ID NO:1 or its complement including at least one Seq-40 polymorphic site selected from the group consisting of the Seq-40 polymorphic sites at positions 194, 601, 1029, 1038, 1074, 2106, 2185, 2359, 2663 and 2796 wherein said Seq-40 polymorphic site or sites is occupied by at least one allele selected from the group consisting of A at position 194, G at position 601, A at position 1029, G at position 1038, C at position 1074 A at position 2106, A at position 2185, T at position 2359, G at position 2663 and A at position 2796
A method for classifying a nucleic acid molecule encoding Seq-40 or a fragment thereof from an individual for diagnostic or prognostic purposes, comprising
- determining the identity of a nucleotide from said nucleic acid which corresponds to the nucleotide occupying at least one Seq-40 polymorphic site selected from the group consisting of the polymorphic sites at positions 194, 601, 1029, 1038, 1074, 2106, 2185, 2359, 2663 and 2796 of SEQ ID NO:1.
A method of haplotype determination in an individual for diagnostic or prognostic purposes, comprising
- determining a nucleotide from said nucleic acid which corresponds to the nucleotide occupying more than one Seq-40 polymorphic sites selected from the group consisting of the polymorphic sites at positions:
- (a) 194 and 1038
- (b) 1038 and 2185
- (c) 601 and 1038
- (d) 194 and 2185
- (e) 601 and 1038 and 2359
- (f) 194 and 601 and 1038
- (g) 601 and 2185
- (h) 194 and 601 and 2185
- (i) 1038 and 2185 and 2359
- (j) 601 and 2185 and 2359
- (k) 2185 and 2359
- (l) 194 and 2185 and 2359
- (m) 2106 and 2185
- of SEQ ID NO:1 on a single chromosome
A method of evaluating the propensity of a patient to develop schizophrenia comprising:
- determining a nucleotide from a nucleic acid obtained from said patient which corresponds to the nucleotide occupying one or more Seq-40 polymorphic sites at positions
- (a) 194 and 1038
- (b) 1038 and 2185
- (c) 601 and 1038
- (d) 194 and 2185
- (e) 601 and 1038 and 2359
- (f) 194 and 601 and 1038
- (g) 601 and 2185
- (h) 194 and 601 and 2185
- (i) 1038 and 2185 and 2359
- (j) 601 and 2185 and 2359
- (k) 2185 and 2359
- (l) 194 and 2185 and 2359
- (m) 2106 and 2185
- of SEQ ID NO:1 on a single chromosome, and
- evaluating whether the patient has a propensity to develop schizophrenia.
96 A method of determining the frequency in a population of a Seq-40 polymorphism, comprising:
- a) genotyping individuals from said population for said polymorphism according to the method of claim 49;
- and
- b) determining the proportional representation of said polymorphism in said population.
A method of estimating the frequency of a haplotype for a set of polymorphic markers in a population, comprising:
- a) genotyping each individual in said population for at least one Seq-40 polymorphism selected from the group consisting of the polymorphic sites at positions 194, 601, 1029, 1038, 1074, 2106, 2185, 2359, 2663 and 2796;
- b) genotyping each individual in said population for a second polymorphic marker by determining the identity of the nucleotides at said second polymorphic marker for both copies of said second polymorphic marker present in the genome;
- and
- c) applying a haplotype determination method to the identities of the nucleotides determined in steps a) and b) to obtain an estimate of said frequency.
The method of detecting an association between an allele and a phenotype, comprising the steps of:
- a) determining the frequency of at least one Seq-40 polymorphism in a trait positive population according to the method of claim 96;
- b) determining the frequency of said Seq-40 polymorphism in a control population according to the method of claim 96;
- and
- c) determining whether a statistically significant association exists between said allele and said phenotype.
A diagnostic kit comprising the required components for the determination of the of the identity of the nucleotide or nucleotides occupying a Seq-40 polymorphic site in small volumes in a self contained kit.
An antibody selected from the group of antibodies consisting of:
- (a) an antibody to an epitope comprising amino acid position 265 of SEQ ID NO 2 capable of distinguishing an isoleucine from a valine at that amino acid position;
- or
- (b) an antibody to an epitope comprising amino acid position 291 of SEQ ID NO 2 capable of distinguishing a tyrosine from an cysteine at that amino acid position;
Dependencies are inferred from the claim text.