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Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder

Abstract

The gene for the synaptic vesicle docking fusion protein, synaptosomal-associated protein of 25 kDa (SNAP-25), has been implicated in the etiology of attention-deficit hyperactivity disorder (ADHD) based on the mouse mutant strain coloboma. This neutron-irradiation induced mouse strain is hemizygous for the deletion of the SNAP-25 gene and displays spontaneous hyperactivity that is responsive to dextroamphetamine. Because of these characteristics, this strain has been suggested to be a mouse model for ADHD. We identified using single stranded conformational polymorphism analysis (SSCP) four DNA sequence variants in the 3′ untranslated region of the human SNAP-25 gene. We searched for polymorphisms in the 3′ untranslated region because the intron/exon structure of this gene has not yet been determined. We tested for linkage of this gene and ADHD using two of the identified polymorphisms that change a restriction enzyme recognition site. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test in a sample of 97 small nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We observed biased transmission of the haplotypes of the alleles of these two polymorphisms. Our findings are suggestive of a role of this gene in ADHD.

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Acknowledgements

This work was supported by grants from the National Alliance for Research in Schizophrenia and Affective Disorders (CLB and JLK), The Hospital for Sick Children Psychiatric Endowment Fund, National Health Research Development Program of Health Canada (6606-5612-401, RS) and the Medical Research Council of Canada (MT14336 and PG11121). We thank an anonymous reviewer for helpful suggestions.

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Correspondence to C L Barr.

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Barr, C., Feng, Y., Wigg, K. et al. Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder. Mol Psychiatry 5, 405–409 (2000). https://doi.org/10.1038/sj.mp.4000733

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