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

Direct link
Reconstruction of Ancestral Haplotypes in a 12-Generation Schizophrenia Pedigree
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
2004 (English)In: Psychiatric Genetics, ISSN 0955-8829, Vol. 14, no 1, 1-8 p.Article in journal (Refereed) Published
Abstract [en]

We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 10p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.

Place, publisher, year, edition, pages
2004. Vol. 14, no 1, 1-8 p.
Keyword [en]
psychiatric genetics, schizophrenia, ancestral haplotypes, susceptibility loci
National Category
URN: urn:nbn:se:uu:diva-93324DOI: 10.1097/01.ypg.0000084941.07075.f9PubMedID: 15091309OAI: oai:DiVA.org:uu-93324DiVA: diva2:166769
Available from: 2005-09-01 Created: 2005-09-01 Last updated: 2010-02-08Bibliographically 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 Biology
In the same journal
Psychiatric Genetics

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: 221 hits
ReferencesLink to record
Permanent link

Direct link