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	Vanti WB, 200314559210
Citation	Vanti W. B., Muglia P., Nguyen T., Cheng R., Kennedy J. L., George S. R. and O'Dowd B. F. (2003) "Discovery of a null mutation in a human trace amine receptor gene." Genomics, 82(5): 531-6.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	224 cases, 84 controls for allelic chi-aquare test; 41 families for TDT test
Predominant Ethnicity	Caucasian
Population	Canada
Age Group	Adults

Detail Info

Summary	G-protein-coupled receptors (GPCRs) are important mediators of signal transduction, and mutations in GPCR-encoding genes can lead to disease states. Here they describe a null mutation in an orphan GPCR-encoding gene that is predicted to inactivate completely the encoded receptor. The TA₃ receptor is a putative member of the recently described mammalian trace amine receptor family, and it is expressed in the pituitary gland and skeletal muscle. They tested for the presence of the mutant form of TA₃ (named TA₃-TR) in a normal population, as well as in two disease groups (ADHD and bipolar affective disorder). They found TA₃-TR to be commonly expressed in all groups, with ~20% allele frequency. They did not find any statistically significant correlation between either disease and the presence of TA₃-TR.
Total Sample	The third sample comprised 224 adult ADHD patients, and for 124 of these patients DNAs from family members were also available.
Sample Collection	Three independent samples were screened for the presence of TA₃-TR. One sample was made up of healthy controls collected from staff and students at the Centre for Addiction and Mental Health (CAMH). One sample consisted of 105 patients with bipolar disorder that were collected at the Bipolar Clinic of the CAMH (Clarke Site), of which details were previously described (Vincent, J.B. et al, 1999). The third sample comprised 224 adult ADHD patients, and for 124 of these patients DNAs from family members were also available. The assessment and the demographic characteristics of the adult ADHD sample were previously described in detail (Muglia, P. et al, 2002). In short, the ethnicity of probands was 97% mixed European Caucasian.
Technique	The full-length sequence of TA₃ was amplified from a mixture of human genomic DNA from three individuals using a 5'-flanking oligonucleotide primer spanning the start codon and a 3'-flanking oligonucleotide primer ending at the stop codon. PCR products were extracted with phenol and chloroform, precipitated with ethanol, and electrophoresed on a low-melting point agarose gel. Products in the expected size range were ligated into the EcoRV site of pcDNA3 (Invitrogen, Carlsbad, CA, USA) and sequenced. To genotype human genomic DNA samples, the allelic variant assay was performed by PCR. For more details, please refer to the original publication.
Analysis Method	The frequencies of the TA₃-WT and TA₃-TR alleles and respective genotypes were compared between the healthy individuals and the two samples made of bipolar and ADHD patients using a X² statistic. In addition, on the adult ADHD probands for which family members were available, a family-based association analysis of TA₃-TR was performed. The family-based analysis was performed using a TDT via the STDT program. TDT calculates the number of transmissions of the alleles from the heterozygous parents to the affected probands and compares this number to the result expected by chance.
Result Description	The allele frequency of TA₃-TR was approximately 20% in all three groups. The X² statistic showed no significant differences between each disease group and the controls in either allele frequency or genotype frequency. In addition, the Transmission Disequilibrium Test (TDT) was used to perform the ADHD family-based association study. In this study, there were 41 families with one heterozygous parent and those were used in the TDT analysis, which did not reveal biased transmissions of the TA3 alleles (data not shown).

Other variant reported by this study (count: 1)

Genes reported by this study (count: 1)