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Screening of candidate genes related to myelination for mutations associated with schizophrenia

Williams, N.M., Spurlock, G., Williams, H., Norton, N., Davis, K.L., Buxbaum, J.D., Haroutunian, V., Saunders, R., Cardno, A.G., McCarthy, G., O'Donovan, M.C. and Owen, M.J. 2001. Screening of candidate genes related to myelination for mutations associated with schizophrenia. American Journal of Medical Genetics - Neuropsychiatric Genetics 105 (7) , p. 589.

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Hakak and colleagues recently used DNA microarray analysis to assay the expression levels of over 6000 genes in the postmortem dorsolateral prefrontal cortex of 12 schizophrenics and matched controls. A total of 89 genes that are involved in a range of biological processess, including synaptic plasticity and neuronal development, were reported to show an altered expression profile in schizophrenics. However, their most notable finding was the differential expression of a number of genes related to myelination (MAL, CNP, MAG, transferin gelsolin and ErbB3), suggesting a disruption in oligodendrite function in schizophrenia. We have now screened each of these 6 genes for sequence variants using DHPLC and sequencing. All identified SNP's have been genotyped by primer extension and their allele frequencies estimated in an association sample of 174 DSMIV schizophrenic patients and 174 matched controls by a method of DNA pooling based on the ABI SnaPshot™ assay. SNP's with a significant difference in allele frequencies were then typed in a second sample of similar size by the same pooling method. Only SNP's that yielded significant results in both samples were subsequently genotyped individually in the same sample to confirm the allelic association. A full report of the SNP's identified and the results of the association analysis will be presented.

Item Type: Article
Status: Published
Schools: Medicine
Last Modified: 30 Jan 2020 15:32

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