Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Haplotype analysis of SNAP-25 suggests a role in the aetiology of ADHD
AU - Mill, J.
AU - Richards, S.
AU - Knight, Jo
AU - Curran, S.
AU - Taylor, Eleanor
AU - Asherson, Philip
PY - 2004/8
Y1 - 2004/8
N2 - Several lines of evidence suggest a role for SNAP-25 (synaptosomal-associated protein of 25 kDa) in the genetic aetiology of ADHD. Most notable is the coloboma mouse mutant, which displays spontaneous hyperactivity and is hemizygous for a deletion spanning this gene. We have screened the SNAP-25 gene using denaturing high-performance liquid chromatography and sequencing, and genotyped six polymorphic single-nucleotide polymorphisms and two microsatellites in a clinically ascertained sample of 188 probands. Several markers were found to show association with ADHD, both individually and in combination with other markers to form multimarker haplotypes. Analyses of transmission by parental sex suggested that the association of SNAP-25 with ADHD is largely due to transmission of alleles from paternal chromosomes to affected probands, suggesting that this locus may be subject to genomic imprinting. Overall our data provide some evidence for a role of this gene in ADHD, although the precise causal functional variant is yet to be ascertained.
AB - Several lines of evidence suggest a role for SNAP-25 (synaptosomal-associated protein of 25 kDa) in the genetic aetiology of ADHD. Most notable is the coloboma mouse mutant, which displays spontaneous hyperactivity and is hemizygous for a deletion spanning this gene. We have screened the SNAP-25 gene using denaturing high-performance liquid chromatography and sequencing, and genotyped six polymorphic single-nucleotide polymorphisms and two microsatellites in a clinically ascertained sample of 188 probands. Several markers were found to show association with ADHD, both individually and in combination with other markers to form multimarker haplotypes. Analyses of transmission by parental sex suggested that the association of SNAP-25 with ADHD is largely due to transmission of alleles from paternal chromosomes to affected probands, suggesting that this locus may be subject to genomic imprinting. Overall our data provide some evidence for a role of this gene in ADHD, although the precise causal functional variant is yet to be ascertained.
KW - Attention Deficit Disorder with Hyperactivity
KW - Base Sequence
KW - DNA Primers
KW - Exons
KW - Family
KW - Female
KW - Genetic Markers
KW - Genotype
KW - Haplotypes
KW - Humans
KW - Male
KW - Membrane Proteins
KW - Nerve Tissue Proteins
KW - Polymorphism, Genetic
KW - Polymorphism, Single Nucleotide
KW - Promoter Regions, Genetic
KW - Synaptosomal-Associated Protein 25
U2 - 10.1038/sj.mp.4001482
DO - 10.1038/sj.mp.4001482
M3 - Journal article
C2 - 15007392
VL - 9
SP - 801
EP - 810
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 8
ER -