Fine Mapping of the Schizophrenia Susceptibility Locus on Chromosome 1q22 (original) (raw)
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Research Articles| June 05 2003
aDepartment of Genetics, Rutgers University, Piscataway, N.J., and
bDepartment of Psychiatry, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, N.J., USA;
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aDepartment of Genetics, Rutgers University, Piscataway, N.J., and
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cGenetics Section, Schizophrenia Research Program, Centre for Addiction and Mental Health, Queen Street Division, and
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cGenetics Section, Schizophrenia Research Program, Centre for Addiction and Mental Health, Queen Street Division, and
dDepartment of Psychiatry, University of Toronto, Toronto, Canada
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cGenetics Section, Schizophrenia Research Program, Centre for Addiction and Mental Health, Queen Street Division, and
dDepartment of Psychiatry, University of Toronto, Toronto, Canada
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Hum Hered (2003) 54 (4): 199–209.
Abstract
Schizophrenia is a serious neuropsychiatric illness estimated to affect approximately 1% of the general population. As part of a genome scan for schizophrenia susceptibility loci, we have previously reported a maximum heterogeneity four-point lod score of 6.50 on chromosome 1q21-22 in a group of 22 medium-sized Canadian families, selected for study because multiple relatives were clinically diagnosed with schizophrenia or schizoaffective disorder. We have now conducted fine mapping of this locus in the same set of individuals using 15 genetic markers spanning an ∼15-cM interval. Parametric linkage analysis with GENEHUNTER v2.1 and VITESSE v2.0 produced a maximum multipoint heterogeneity lod score of 6.50, with a Zmax-1 support interval of <3 cM, corresponding to ∼1 Mb. Physical mapping and sequence analysis from this region confirmed the presence of an ∼81-kb tandem duplication, containing low-affinity IgG receptor genes and heat shock protein genes. The sequences of the two copies of this duplication are ∼97% identical, which has led to the collapse of the two copies into one in the June 2002 NCBI Build 30 of the Human Genome. This duplication may be involved in genomic instability, leading to gene deletion, and so presents an intriguing candidate locus for schizophrenia susceptibility.
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© 2002 S. Karger AG, Basel
2003
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