ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Mazei-Robison MS, 200516171832
Citation	Mazei-Robison M. S., Couch R. S., Shelton R. C., Stein M. A. and Blakely R. D. (2005) "Sequence variation in the human dopamine transporter gene in children with attention deficit hyperactivity disorder." Neuropharmacology, 49(6): 724-36.
Study Design
Study Type	Mutational study
Sample Size	70 subjects in Vanderbilt cohort; 42 subjects in Chicago cohort
Predominant Ethnicity	Caucasian
Population	USA
Gender	Vanderbilt cohort: 79% male, 21% female; University of Chicago cohort: 74% male
Age Group	Children/Adolescents : Vanderbilt cohort: 6-17 years; University of Chicago cohort: not mentioned

Detail Info

Summary	Two separate ADHD cohorts (N=70 and N=42) were screened and sampled for both status of the 3'VNTR and for common/novel genomic variants. They found evidence of increased DAT variation in African-USAn subjects as well as in predominately hyperactive-impulsive probands. Cumulatively, multiple hDAT sequence variants were identified, including five novel variants, as well as one nonsynonymous single nucleotide polymorphism (SNP), converting Ala559 to Val (A559V). A559V was identified in two Caucasian male siblings with ADHD and both subjects were homozygous for the ADHD-associated, 10-repeat 3'VNTR allele.
Total Sample	Vanderbilt cohort: Buccal cell samples were collected from 70 subjects (50 unrelated, 10 affected sib pairs) between the ages of 6 and 17 years under the auspices of the Center for Child Development and Clinical Trials Center at the Vanderbilt University Medical Center. The mean age of the cohort was 10.5 (SD=0.3) years and was 79% male and 21% female. Most subjects were Caucasian (83%), with African-USAn representation (17%) consistent with the population of the middle Tennessee area. Chicago cohort: 42 subjects were collected at Children's National Medical Center and examined at the University of Chicago. Similar to the Vanderbilt cohort, the majority of the subjects were male (74%) and Caucasian (76%), and were diagnosed with ADHD-CT (57%).
Sample Collection	Buccal cell samples were collected from 70 subjects (50 unrelated, 10 affected sib pairs) between the ages of 6 and 17 years under the auspices of the Center for Child Development and Clinical Trials Center at the Vanderbilt University Medical Center. A second cohort of ADHD subjects were collected at Children's National Medical Center and examined at the University of Chicago.
Diagnosis Description	Vanderbilt cohort: The Kiddie-SADS-Present and Lifetime Version (Kaufman et al., 1997) was used to determine that DSM-IV criteria for predominantly inattentive type, predominantly hyperactive- impulsive type, or combined inattentive and hyperactive- impulsive type ADHD (ADHD-CT) were met (Ambrosini, 2000). The Conner's Adult ADHD rating scale (CAARS-S:L) was administered to selected adult relatives of children with ADHD to ascertain ADHD status (Conners et al., 1998). University of Chicago cohort: All 42 subjects analyzed in this study completed a semistructured diagnostic interview and met DSM-IV criteria for ADHD (Stein et al., 2003). Genomic DNA was extracted from whole blood using a PureGene kit (Gentra systems).
Technique	Oligonucleotide primers (Invitrogen, Carlsbad, CA) were designed to amplify exons 2e15 of hDAT, comprising the entire coding sequence as well as the intron/ exon boundaries. The amplification of the 3'VNTR was completed using primers described by Vandenbergh et al., ~100 ng of genomic DNA, 0.2 U Amplitaq Gold, 5 nmol dNTP, 5 pmol of each primer and 5% DMSO and the following PCR conditions: 94 ^oC for 5 min followed by 30 cycles of 94 ^oC for 30 s, 62 ^oC for 30 s, 72 ^oC for 30 s and a final extension of 72 ^oC for 10 min PCR products were verified on a 2% agarose gel from which repeat number was determined. PCR products from subject DNA were mixed 1:1 with a reference DNA PCR product of the same amplicon whose sequence matches that of a reference hDAT sequence (GenBank/EMBL hDAT accession number AF119117). Please refer to the original publication for more descriptions.
Result Description	They found evidence of increased DAT variation in African-USAn subjects as well as in predominately hyperactive-impulsive probands. Cumulatively, multiple hDAT sequence variants were identified, including five novel variants, as well as one nonsynonymous single nucleotide polymorphism (SNP), converting Ala559 to Val (A559V). A559V was identified in two Caucasian male siblings with ADHD and both subjects were homozygous for the ADHD-associated, 10-repeat 3' VNTR allele.

SNPs reported by this study (count: 6)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs28364996				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend
rs28364999				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend
rs28364998				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend
rs28364997				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend
rs28363074				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend
rs28363166				novel variant identified in candidate gene hDAT novel variant identified in candidate gene hDAT	Trend

Genes reported by this study (count: 1)