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Haplotype analysis and identification of genes for a complex trait: examples from schizophrenia

For more than a decade there has been intensive research into the genetic etiology of schizophrenia, yet it is only recently that the first findings of promising genes associating with the disorder have been reported. Linkage analyses in families collected from different populations have provided relatively well defined genomic loci. These have been typically followed by fine mapping studies using single nucleotide polymorphisms (SNPs). A number of analysis programs have been produced to test SNPs and their haplotypes for association. Typically association has been established to specific haplotypes representing an allelic variant of the corresponding gene. The inherent problem of multiple testing in the analysis of haplotypes needs to be addressed fully, to determine if any of these recent findings can be considered as confirmed susceptibility genes for schizophrenia. However, informative haplotypes have provided a way to define allelic variants of genes associated with schizophrenia in numerous study samples, and are a useful tool in characterizing the extent of allelic diversity of putative schizophrenia susceptibility genes within different populations.