A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder.
Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning di...
| मुख्य लेखकों: | , , , , , , , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
2008
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| _version_ | 1826272265988210688 |
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| author | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W |
| author_facet | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W |
| author_sort | Pickard, B |
| collection | OXFORD |
| description | Underactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression. |
| first_indexed | 2024-03-06T22:09:50Z |
| format | Journal article |
| id | oxford-uuid:516db0d7-c255-4118-bbc9-f401e1b70f8d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:09:50Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:516db0d7-c255-4118-bbc9-f401e1b70f8d2022-03-26T16:19:30ZA common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:516db0d7-c255-4118-bbc9-f401e1b70f8dEnglishSymplectic Elements at Oxford2008Pickard, BKnight, HHamilton, RSoares, DWalker, RBoyd, JMachell, JMaclean, AMcGhee, KCondie, APorteous, DSt Clair, DDavis, IBlackwood, DMuir, WUnderactivity of the glutamatergic system is an attractive model for the pathophysiology of several major mental illnesses. We previously described a chromosome abnormality disrupting the kainate class ionotropic glutamate receptor gene, GRIK4/KA1, in an individual with schizophrenia and learning disability (mental retardation). We also demonstrated in a case-control study that two physically separated haplotypes within this gene were significantly associated with increased risk of schizophrenia and decreased risk of bipolar disorder, respectively. The latter protective haplotype was located at the 3' end of the gene. We now report the identification from carriers of the protective haplotype of a deletion variant within the 3' untranslated region of the gene. The deletion allele also was found to be negatively associated with bipolar disorder in both initial (P = 0.00000019) and replication (P = 0.0107) case-control studies. Expression studies indicated that deletion-carrying mRNA transcripts were relatively more abundant. We postulate that this may be a direct consequence of the differences in the RNA secondary structures predicted for the insertion and deletion alleles. These data suggest a mechanism whereby the genetic protective effect is mediated through increased kainate receptor expression. |
| spellingShingle | Pickard, B Knight, H Hamilton, R Soares, D Walker, R Boyd, J Machell, J Maclean, A McGhee, K Condie, A Porteous, D St Clair, D Davis, I Blackwood, D Muir, W A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_full | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_fullStr | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_full_unstemmed | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_short | A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder. |
| title_sort | common variant in the 3 utr of the grik4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder |
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