Disease relevance of DRD5

• OBJECTIVE: To investigate the role of the dopamine receptor genes, DRD1, DRD3, and DRD5 in the pathogenesis of migraine [1].
• Allele 2 of a DRD5 dinucleotide repeat was significantly associated with blepharospasm [2].

Psychiatry related information on DRD5

• Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes [3].
• These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder [4].
• We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M) [4].
• The human DRD5 gene is located at 4p15.1-p15.33, centromeric to the location of the Huntington's disease locus although not in the obligate area containing the HD gene [5].
• Antisociality, substance dependence, and the DRD5 gene: a preliminary study [6].

High impact information on DRD5

• An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele [3].
• We have investigated 12 U.K. families with Wolfram syndrome, and we report confirmation of linkage to chromosome 4p, with a maximum two-point LOD score of 4.6 with DRD5, assuming homogeneity, and of 5.1, assuming heterogeneity [7].
• To determine whether mutations in the D5 dopamine receptor gene (DRD5) are associated with schizophrenia, the gene was examined in 78 unrelated schizophrenic individuals (156 DRD5 alleles) [8].
• We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053) [9].
• Correlation between D' and physical distance was observed between markers at DAT1 and DRD5 for distances less than 50 kb [10].

Biological context of DRD5

• Thus, the human genome contains at least two DRD5 pseudogenes, consistent with in situ human chromosomal hybridization analysis which reveals the presence of two pseudogenes [11].
• The deduced amino acid sequences for these genes, PG-1 and PG-2, share 91% and 92% identity to DRD5, respectively [11].
• Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1 [12].
• We identified a cosmid clone with exact sequence homology to part of the human dopamine D5 receptor gene (DRD5) after screening a cosmid library with the human DRD1 gene [12].
• For DRD5, data from five studies, with a total of 340 informative meioses, were combined yielding a pooled odds ratio of 1.57 (95% CI 1.25-1.96, =8.28 x 10 ) [13].

Anatomical context of DRD5

• Further localization of the DRD5 gene was carried out through the isolation and analysis of yeast artificial chromosomes, fluorescence in situ suppression hybridization to human metaphase chromosomes, and analysis of a panel of somatic cell hybrids subdividing human chromosome 4 into nine regions [5].
• OBJECTIVE: To investigate a possible role of DYT1 polymorphisms, a CA repeat in the D5 receptor gene (DRD5), the human leukocyte antigen (HLA)-DRB locus, and four polymorphisms in the homocysteine metabolism in the pathogenesis of F-ITD [14].

Associations of DRD5 with chemical compounds

• In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5 [15].
• An association study of DRD5 with smoking initiation and progression to nicotine dependence [16].

Other interactions of DRD5

• Localization of the CCK receptors with two dopamine receptors, DRD5 (4p15.1-p15.3) and DRD4 (11p15), provides the interesting possibility of coinvolvement in neuropsychiatric or CNS illnesses [17].
• Two of these dopamine receptors (DRD1 and DRD5) are encoded by intronless genes [11].
• We were unable to detect a significant association with any of the polymorphisms genotyped, although there was a trend for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122 bp marker allele [18].
• Transmission of the 'associated' alleles at DAT1 and DBH is stronger in familial cases, RR(DAT1)=1.29 (1.04-1.59), RR(DBH)=1.49 (1.10-2.00), but for DRD5, transmission is stronger in non-familial cases, RR=1.59 (1.05-2.42) [19].
• We have previously reported that the human genome contains the two pseudogenes psi DRD5-1, and psi DRD5-2, and that each share 94% homology when compared with the functional gene DRD5 [20].

Analytical, diagnostic and therapeutic context of DRD5

• Human genomic DNA was amplified by PCR with oligodeoxyribonucleotides (oligos) based on the DRD5 nucleotide (nt) sequence [11].
• In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter [4].
• To confirm these data, we performed a case-control study of the microsatellite (CT/GT/GA)(n) at the DRD5 locus in 104 Italian CD patients and 104 healthy controls [21].
• We questioned whether these pseudogenes were transcribed, since transcription of either of these pseudogenes could result in false interpretation of in-situ hybridization and Northern blot analysis, using the DRD5 as a probe [20].

References