Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval

Details

Serval ID
serval:BIB_422FCB8DEDDB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval
Journal
European Journal of Human Genetics
Author(s)
Levi  A., Kohn  Y., Kanyas  K., Amann  D., Pae  C. U., Hamdan  A., Segman  R. H., Avidan  N., Karni  O., Korner  M., Jun  T. Y., Beckmann  J. S., Macciardi  F., Lerer  B.
ISSN
1018-4813 (Print)
Publication state
Published
Issued date
06/2005
Volume
13
Number
6
Pages
763-71
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
Abstract
We previously reported an autosomal scan for schizophrenia susceptibility loci in a systematically recruited sample of Arab Israeli families. The scan detected significant evidence for linkage at chromosome 6q23 with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) and a multipoint parametric LOD score of 4.16. In order to refine this finding we typed 42 additional microsatellite markers on chromosome 6q between D6S1570 (99.01 cM from the pter) and D6S281 (190.14 from the pter) in the same sample (average intermarker distance approximately 1.7 cM). In the 23 cM region between D6S1715 and D6S311, markers were more closely spaced ( approximately 1.1 cM). Multipoint nonparametric and parametric and single point linkage analyses were performed. The peak NPL rose to 4.98 (P=0.00000058) at D6S1626 (136.97 cM), immediately adjacent to D6S292 (NPL 4.98, P=0.00000068), the marker that gave the highest NPL in the original genome scan, under the broad diagnostic category. The putative susceptibility region (NPL-1) was reduced from 12.0 to 4.96 cM. The peak multipoint parametric LOD score was 4.63 at D6S1626 under a dominant genetic model, core diagnostic category and the LOD-1 interval was 2.10 cM. The maximum single point LOD score (3.55, theta=0.01) was also at D6S1626 (dominant model, core diagnostic category). Increased evidence for linkage in the same sample as in the original genome scan and consistent localization of the linkage peak add further support for the presence of a schizophrenia susceptibility locus at chromosome 6q23. Moreover, the markedly reduced linkage interval greatly improves prospects for identifying a schizophrenia susceptibility gene within the implicated region.
Keywords
Arabs/genetics Chromosome Mapping *Chromosomes, Human, Pair 6 *Genetic Predisposition to Disease Humans Israel *Linkage (Genetics) Microsatellite Repeats Schizophrenia/*genetics
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 17:17
Last modification date
20/08/2019 14:44
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