title: Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval.
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.
authors.affiliation: Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Levi
authors.forename: Yoav
authors.initials: Y
authors.lastname: Kohn
authors.forename: Kyra
authors.initials: K
authors.lastname: Kanyas
authors.forename: Daniela
authors.initials: D
authors.lastname: Amann
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Pae
authors.forename: Adnan
authors.initials: A
authors.lastname: Hamdan
authors.forename: Ronnen H
authors.initials: RH
authors.lastname: Segman
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Osnat
authors.initials: O
authors.lastname: Karni
authors.forename: Mira
authors.initials: M
authors.lastname: Korner
authors.forename: Tae-Yun
authors.initials: TY
authors.lastname: Jun
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Fabio
authors.initials: F
authors.lastname: Macciardi
authors.forename: Bernard
authors.initials: B
authors.lastname: Lerer
mesh_terms: D018912:Arabs / Q000235:genetics; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel; D018895:Microsatellite Repeats; D012559:Schizophrenia / Q000235:genetics*