uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Human QKI, a New Candidate Gene for Schizophrenia Involved in Myelination
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
Show others and affiliations
2005 (English)In: American journal of medical genetics. Part B, Neuropsychiatric genetics, ISSN 1552-4841, Vol. 141B, no 1, 84-90 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2005. Vol. 141B, no 1, 84-90 p.
Keyword [en]
mRNA-expression, haplotype investigation, fine-mapping, large pedigree
National Category
URN: urn:nbn:se:uu:diva-93325DOI: 10.1002/ajmg.b.30243PubMedID: 16342280OAI: oai:DiVA.org:uu-93325DiVA: diva2:166770
Available from: 2005-09-01 Created: 2005-09-01 Last updated: 2010-02-02Bibliographically approved
In thesis
1. Finding Genes for Schizophrenia
Open this publication in new window or tab >>Finding Genes for Schizophrenia
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Schizophrenia is one of our most common psychiatric diseases. It severely affects all aspects of psychological functions and results in loss of contact with reality. No cure exists and the treatments available today produce only partial relief for disease symptoms. The aim of this work is to better understand the etiology of schizophrenia by identification of candidate genes and gene pathways involved in the development of the disease.

In a preliminarily study, the effects of medication and genetic factors were investigated in a candidate gene, serotonin 2C receptor. This study distinguished pharmacological effects, caused by neuroleptics, and/or genetic effects, caused by unique polymorphisms, from other effects responsible for mRNA expression changes on candidate genes.

The core of the thesis describes a new candidate gene for schizophrenia, the quaking homolog, KH domain RNA binding (mouse) or QKI, located on chromosome 6q26-q27. The identification of QKI is supported by previous linkage studies, current association studies and mRNA expression studies using three different sample sets. The investigated samples included a 12-generation pedigree with 16 distantly related schizophrenic cases and their parents, 176 unrelated nuclear families with at least one affected child in each family and human brain autopsies from 55 schizophrenic cases and from 55 controls. Indirect evidence showing involvement of QKI in myelin regulation of central nervous system is presented. Myelin plays an important role in development of normal brains and disruption of QKI might lead to schizophrenia symptoms.

In a forth sample set, including extended pedigrees originated from a geographically isolated area above the Arctic Circle, in northeast Sweden, two additional schizophrenia susceptibility loci were identified, 2q13 and 5q21. Both these regions have previously been highlighted as potential schizophrenia loci in several other investigations, including a large Finnish study. This suggests common schizophrenia susceptibility loci for Nordic populations.

A pilot investigation including a genome wide haplotype analysis is presented. This statistical strategy could be further developed and applied to the artic Swedish families, including analysis of 900 microsatellites and 10,000 SNPs.

These findings will facilitate the understanding of the schizophrenia etiology and may lead to development of more efficient treatments for patients that suffer from schizophrenia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 50 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 78
psychiatric genetics, QKI, large pedigree, haplotype investigation, mRNAexpression, genetic linkage, myelin, HTR2C
National Category
Biological Sciences
urn:nbn:se:uu:diva-5894 (URN)91-554-6308-8 (ISBN)
Public defence
2005-09-22, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 13:15 (English)
Available from: 2005-09-01 Created: 2005-09-01 Last updated: 2009-03-31Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Jazin, Elena
By organisation
Evolutionary BiologyDepartment of Genetics and Pathology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 218 hits
ReferencesLink to record
Permanent link

Direct link