Methods and systems for facilitating the diagnosis and treatment of schizophrenia
AssigneeVanderbult University
InventorsPat Ressler Levitt, Venkata Chowdari Kodavali, Vishwajit Laxmikant Nimgaonkar, Karoly Mirnics
Life of this patent
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Abstract
A method of diagnosing, assessing susceptibility, and/or treating schizophrenia involving the observation of regulator of G-protein signaling 4 (RGS4) levels in a subject. Embodiments of the present invention include increasing RGS4 expression levels in the cortex, either by chemical means or by genetic complementation (e.g. gene therapy).
Claims45
An isolated and substantially purified DNA sequence comprising a sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and contiguous portions thereof.
A polynucleotide sequence that is complementary to a sequence selected from the group consisting of SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7, and SEQ ID NO:
- 8, and contiguous portions thereof.
A polynucleotide sequence that is complementary to SEQ ID NO:3, wherein SEQ ID NO:
- 3 contains one or more variations selected from the group consisting of
- a T at nucleotide base number 4121;
- an A at nucleotide base number 4123;
- a C at nucleotide base number 4368;
- a C at nucleotide base number 4621;
- a T at nucleotide base number 4790;
- a T at nucleotide base number 4816;
- a T at nucleotide base number 4970;
- a G at nucleotide base number 5055;
- an A at nucleotide base number 5295;
- an A at nucleotide base number 5695;
- a T at nucleotide base number 7375;
- an A at nucleotide base number 7759;
- an A at nucleotide base number 8596;
- base numbers 9603-9609 are absent;
- an A at nucleotide base number 9892;
- an A at nucleotide base number 9963;
- an A at nucleotide base number 10132;
- a C at nucleotide base number 11056;
- a T at nucleotide base number 11091;
- an A at nucleotide base number 11106;
- a T at nucleotide base number 11774;
- an A at nucleotide base number 12143;
- a T at nucleotide base number 12145;
- a G at nucleotide base number 14367;
- base number 17028 is absent;
- and
- a T at nucleotide base number 17630;
A polynucleotide sequence that is complementary to SEQ ID NO:4, wherein SEQ ID NO:
- 4 contains a C at nucleotide base number 199.
A polynucleotide sequence that is complementary to SEQ ID NO:5, wherein SEQ ID NO:
- 5 contains a T at nucleotide base number 153.
A polynucleotide sequence that is complementary to SEQ ID NO:6, wherein SEQ ID NO:
- 6 contains an A at nucleotide base number 87.
A polynucleotide sequence that is complementary to SEQ ID NO:7, wherein SEQ ID NO:
- 7 contains a G at nucleotide base number 120.
A polynucleotide sequence that is complementary to SEQ ID NO:8, wherein SEQ ID NO:
- 8 contains a C at nucleotide base number 221.
An expression system comprising a DNA sequence that corresponds to SEQ ID NO:
- 3.
A method for diagnosing schizophrenia in a human, said method comprising:
- obtaining from a patient a DNA sample comprising a RGS4 gene;
- and
- detecting a variation in the RGS4 gene indicating schizophrenia.
A method of determining susceptibility to schizophrenia comprising:
- obtaining from a patient a DNA sample comprising a RGS4 gene;
- and
- detecting a variation in said RGS4 gene indicating susceptibility to schizophrenia.
A method for diagnosing schizophrenia comprising:
- obtaining from a patient to be tested for schizophrenia a sample of tissue;
- measuring RGS4 mRNA levels in said sample;
- and
- determining if there is a reduced level of RGS4 mRNA in the sample.
A method of determining susceptibility to schizophrenia comprising:
- obtaining from a patient to be tested for susceptibility to schizophrenia a sample of tissue;
- measuring RGS4 mRNA levels in said sample;
- and
- determining if there is a reduced level of RGS4 mRNA in the sample.
A method for diagnosing schizophrenia comprising:
- obtaining from a patient to be tested for schizophrenia a sample of tissue;
- measuring RGS4 protein levels in said sample;
- and
- determining if there is a reduced level of RGS4 protein in the sample.
A method of determining susceptibility to schizophrenia comprising:
- obtaining from a patient to be tested for susceptibility to schizophrenia a sample of tissue;
- measuring RGS4 protein levels in said sample;
- and
- determining if there is a reduced level of RGS4 protein in the sample.
A method of treating schizophrenia, said method comprising:
- measuring RGS4 protein or mRNA levels in a patient;
- and
- altering said RGS4 protein levels to provide the patient with an improved psychiatric function.
A kit for diagnosing schizophrenia in a patient, said kit comprising:
- antibodies to RGS4;
- and
- a detector for ascertaining whether said antibodies bind to RGS4 in a sample.
A kit for diagnosing schizophrenia in a patient, said kit comprising:
- a detector of RGS4 transcript levels in a patient;
- and
- a standard to ascertain altered levels of RGS4 transcript in the patient.
An isolated and substantially purified DNA sequence comprising a sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:3 in which nucleotide base number 4121 is an T;
- SEQ ID NO:3 in which nucleotide base number 4123 is an A;
- SEQ ID NO:3 in which nucleotide base number 4368 is a C;
- SEQ ID NO:3 in which nucleotide base number 4621 is a C;
- SEQ ID NO:3 in which nucleotide base number 4790 is a T;
- SEQ ID NO:3 in which nucleotide base number 4816 is a T SEQ ID NO:3 in which nucleotide base number 4970 is a T;
- SEQ ID NO:3 in which nucleotide base number 5055 is a G;
- SEQ ID NO:3 in which nucleotide base number 5295 is an A;
- SEQ ID NO:3 in which nucleotide base number 5695 is an A;
- SEQ ID NO:3 in which nucleotide base number 7375 is a T SEQ ID NO:3 in which nucleotide base number 7759 is an A;
- SEQ ID NO:3 in which nucleotide base number 8596 is a n A;
- SEQ ID NO:3 in which nucleotide base number s 9603-9609 are absent;
- SEQ ID NO:3 in which nucleotide base number 9892 is an A;
- SEQ ID NO:3 in which nucleotide base number 9963 is an A;
- SEQ ID NO:3 in which nucleotide base number 10132 is an A;
- SEQ ID NO:3 in which nucleotide base number 11056 is a C;
- SEQ ID NO:3 in which nucleotide base number 11091 is a T;
- SEQ ID NO:3 in which nucleotide base number 11106 is an A;
- SEQ ID NO:3 in which nucleotide base number 11774 is a T;
- SEQ ID NO:3 in which nucleotide base number 12143 is an A;
- SEQ ID NO:3 in which nucleotide base number 12145 is a T;
- SEQ ID NO:3 in which nucleotide base number 14367 is a G;
- SEQ ID NO:3 in which nucleotide base number 17028 is absent;
- SEQ ID NO:3 in which nucleotide base number 17630 is a T;
- SEQ ID NO:4 in which nucleotide base number 199 is a C;
- SEQ ID NO:5 in which nucleotide base number 193 is a T;
- SEQ ID NO:6 in which nucleotide base number 87 is an A;
- SEQ ID NO:7 in which nucleotide base number 120 is a G;
- SEQ ID NO:8 in which nucleotide base number 221 is a C;
- contiguous portions thereof;
- and perfect complements thereof.
A transgenic mouse whose genome comprises a disruption of the endogenous RGS4 gene, wherein said disruption comprises the insertion of a transgene, and wherein said disruption results in said transgenic mouse not exhibiting normal expression of RGS4 protein.
Dependencies are inferred from the claim text.