Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval.
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.
Levi
Adi
A
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Kohn
Yoav
Y
Kanyas
Kyra
K
Amann
Daniela
D
Pae
Chi-Un
CU
Hamdan
Adnan
A
Segman
Ronnen H
RH
Avidan
Nili
N
Karni
Osnat
O
Korner
Mira
M
Jun
Tae-Yun
TY
Beckmann
Jacques S
JS
Macciardi
Fabio
F
Lerer
Bernard
B
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*