Human QKI, a new candidate gene for schizophrenia involved in myelination
Abstract We have previously shown that chromosome 6q25–6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine‐mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely...
Published in: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics |
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crwiley:10.1002/ajmg.b.30243 2024-09-15T18:26:05+00:00 Human QKI, a new candidate gene for schizophrenia involved in myelination Åberg, Karolina Saetre, Peter Lindholm, Eva Ekholm, Birgit Pettersson, Ulf Adolfsson, Rolf Jazin, Elena 2005 http://dx.doi.org/10.1002/ajmg.b.30243 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajmg.b.30243 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.b.30243 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor American Journal of Medical Genetics Part B: Neuropsychiatric Genetics volume 141B, issue 1, page 84-90 ISSN 1552-4841 1552-485X journal-article 2005 crwiley https://doi.org/10.1002/ajmg.b.30243 2024-08-01T04:22:42Z Abstract We have previously shown that chromosome 6q25–6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine‐mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%). A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P ‐value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI) , was investigated in human brain autopsies from 55 cases and 55 controls using a high‐resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients ( P ‐value 0.0004 and 0.03, respectively). The function of QKI has not been studied in humans, but the mouse homolog is involved in neural development and myelination. In conclusion, we present evidence from three unrelated sample‐sets that propose the involvement of the QKI gene in schizophrenia. The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case‐control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins. Taken together, we propose QKI as a possible target for functional studies related to the role of myelination in schizophrenia. © 2005 Wiley‐Liss, Inc. Article in Journal/Newspaper Northern Sweden Wiley Online Library American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 141B 1 84 90 |
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Wiley Online Library |
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language |
English |
description |
Abstract We have previously shown that chromosome 6q25–6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine‐mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%). A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P ‐value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI) , was investigated in human brain autopsies from 55 cases and 55 controls using a high‐resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients ( P ‐value 0.0004 and 0.03, respectively). The function of QKI has not been studied in humans, but the mouse homolog is involved in neural development and myelination. In conclusion, we present evidence from three unrelated sample‐sets that propose the involvement of the QKI gene in schizophrenia. The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case‐control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins. Taken together, we propose QKI as a possible target for functional studies related to the role of myelination in schizophrenia. © 2005 Wiley‐Liss, Inc. |
format |
Article in Journal/Newspaper |
author |
Åberg, Karolina Saetre, Peter Lindholm, Eva Ekholm, Birgit Pettersson, Ulf Adolfsson, Rolf Jazin, Elena |
spellingShingle |
Åberg, Karolina Saetre, Peter Lindholm, Eva Ekholm, Birgit Pettersson, Ulf Adolfsson, Rolf Jazin, Elena Human QKI, a new candidate gene for schizophrenia involved in myelination |
author_facet |
Åberg, Karolina Saetre, Peter Lindholm, Eva Ekholm, Birgit Pettersson, Ulf Adolfsson, Rolf Jazin, Elena |
author_sort |
Åberg, Karolina |
title |
Human QKI, a new candidate gene for schizophrenia involved in myelination |
title_short |
Human QKI, a new candidate gene for schizophrenia involved in myelination |
title_full |
Human QKI, a new candidate gene for schizophrenia involved in myelination |
title_fullStr |
Human QKI, a new candidate gene for schizophrenia involved in myelination |
title_full_unstemmed |
Human QKI, a new candidate gene for schizophrenia involved in myelination |
title_sort |
human qki, a new candidate gene for schizophrenia involved in myelination |
publisher |
Wiley |
publishDate |
2005 |
url |
http://dx.doi.org/10.1002/ajmg.b.30243 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajmg.b.30243 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.b.30243 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics volume 141B, issue 1, page 84-90 ISSN 1552-4841 1552-485X |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/ajmg.b.30243 |
container_title |
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics |
container_volume |
141B |
container_issue |
1 |
container_start_page |
84 |
op_container_end_page |
90 |
_version_ |
1810466529447247872 |