Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval
Articolo
Data di Pubblicazione:
2005
Citazione:
Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval / A. Levi, Y. Kohn, K. Kanyas, D. Amann, C. U. Pae, A. Hamdan, R. H. Segman, N. Avidan, O. Karni, M. Korner, T. Y. Jun, J. S. Beckmann, F. Macciardi, B. Lerer. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 13:6(2005 Jun), pp. 763-771.
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 (P¼0.000004) 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 (99.01cM from the pter) and D6S281 (190.14 from the pter) in the same sample
(average intermarker distanceB1.7 cM). In the 23cM region between D6S1715 and D6S311, markers were
more closely spaced (B1.1cM). Multipoint nonparametric and parametric and single point linkage
analyses were performed. The peak NPL rose to 4.98 (P¼0.00000058) at D6S1626 (136.97cM),
immediately adjacent to D6S292 (NPL 4.98, P¼0.00000068), 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, h¼0.01) 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
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
A. Levi, Y. Kohn, K. Kanyas, D. Amann, C. U. Pae, A. Hamdan, R. H. Segman, N. Avidan, O. Karni, M. Korner, T. Y. Jun, J. S. Beckmann, F. Macciardi, B. Lerer
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