TREATMENT AND DIAGNOSIS OF EPIGENETIC DISORDERS AND CONDITIONS

摘要

The present disclosure relates generally to the field of epigenetics and in particular epigenetic profiles associated with a pathological condition. The present specification teaches screening of individuals and populations for epigenetic profiles associated with a pathological condition. The epigenetic profiles can be from an intron, an intron/exon boundary or a splicing region. Epigenetic profiles are disclosed from the following sites in the FMR locus: FREE3, intron 2 of FMR1, the genomic FREE2 region as a whole or specific FREE2 fragments including FREE2 (D) or FREE2 (E). Kits and diagnostic assays are also taught herein as are computer programs to monitor changes in epigenetic patterns and profiles. Further enabled herein is a method for screening for agents which can reduce or mask the adverse effects of epigenetic modification and the use of these agents in therapy and prophylaxis.

主权项

1. A method of treating a human subject for a pathological condition associated with the presence of a pre-mutation or a full mutation of the Fragile X Mental Retardation (FMR) genetic locus (FMR1) or a propensity to develop the same comprising:
(a) having genomic DNA isolated from the human subject; (b) having an assay conducted on the isolated genomic DNA, said assay comprising:
1) subjecting the isolated genomic DNA to one or more modifications selected from the group consisting of:
i) contacting with bisulfite for a time and under conditions sufficient to convert non-methylated cytosines to uracils; and,ii) digesting with a methylation-sensitive restriction endonuclease;2) amplifying by PCR:
i) FREE2(D) consisting of the nucleotide sequence set forth in SEQ ID NO: 48; orii) FREE2(E) consisting of the nucleotide sequence set forth in SEQ ID NO: 49;3) determining a difference in the extent of methylation in the isolated genomic DNA from the human subject relative to the extent of methylation in a control genomic DNA sample from a control subject with (CGG)n, wherein n is <40, thereby determining that the human subject has a pathological condition associated with pre-mutation or full mutation of FMR1 or a propensity to develop the same; and (c) treating the human subject by administering to the human subject a pharmacological agent and/or behavioral intervention protocol.