Dopamine D4 Receptor Exon Research Articles

DRD4 Exon 3 Gene Polymorphisms in Patients Diagnosed with Polysubstance Use Disorder and Co-Occurrence of a Depressive Episode.

Background: There has been a noticeable and systematic growth of the use of psychoactive substances over the past few decades. Dual diagnosis is a clinical term referring to the occurrence of psychoactive substance use disorder comorbid with another psychiatric disorder in the same person. The most common type of dual diagnosis is the co-occurrence of alcohol use disorder and mood disorders in the form of a depressive episode. Co-occurrent substance use disorders are frequently influenced by genetic factors. In selecting our area of research, we focused on dopamine and the DRD4 (Dopamine Receptor D4) gene polymorphism as well as associations with personality features. The aim of the study: The aim of the study was to compare DRD4 exon 3 (DRD4 Ex3) gene polymorphisms in patients diagnosed with polysubstance use disorder and co-occurrence of a depressive episode to DRD4 exon 3 gene polymorphisms in patients diagnosed with polysubstance use disorder and without co-occurrence of a depressive episode and a group of healthy volunteers. The study also aimed at establishing associations between personality features and DRD4 exon 3 gene polymorphisms of male patients diagnosed with polysubstance use disorder with co-occurrence of a depressive episode which may present a specific endophenotype of this group of patients. Methods: The study group comprised 602 male volunteers: patients diagnosed with polysubstance use disorder comorbid with a depressive episode (PUD MDD) (n = 95; mean age = 28.29, standard deviation (SD) = 7.40), patients diagnosed with polysubstance use disorder (PUD) (n = 206; mean age = 28.13, SD = 5.97), and controls (n = 301; mean age = 22.13, SD = 4.57). The patients and control subjects were diagnosed by a psychiatrist using the Mini International Neuropsychiatric Interview (MINI), the NEO Five-Factor Personality Inventory (NEO-FFI), and the State-Trait Anxiety Inventory (STAI) questionnaires. An analysis of the DRD4 exon 3 polymorphism was performed. Results: The patients diagnosed with PUD MDD compared to the control group of healthy volunteers showed significantly higher scores on both the STAI status and features scale and the NEO-FFI Neuroticism and Openness Scale, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness NEO-FFI scales. In the DRD4 exon 3 gene polymorphism, the s allele was more frequent in the PUD MDD compared to the l allele, which was less frequent. The results of the 2 × 3 factor analysis of variance (ANOVA) in patients and controls and the variant DRD4 exon 3 interaction were found on the Extraversion Scale and the Conscientiousness Scale of the NEO-FFI. Conclusions: The associations show that psychological factors combined with genetic data create a new area of research on addiction, including the problem of dual diagnosis. However, we want to be careful and draw no definite conclusions at this stage of our research.

Significance of Dopaminergic Gene Variants in the Male Biasness of ADHD

Objective: ADHD is frequently detected in boys though there is no established cause. One possibility is that genes predisposing to ADHD have sexually dimorphic effects. With an aim to find out the reason for this male biasness, contribution of 14 functional polymorphisms was investigated in ADHD subjects. Method: Genomic DNA of probands, their parents, and ethnically matched controls was subjected to analysis of single-nucleotide polymorphisms and variable number of tandem repeats (VNTRs). Results: Case–control analysis revealed significant higher occurrence of DAT1 intron 8 VNTR “5R” allele (p = .028), DBH rs1108580 “A” allele (p = .027), and MAOA-u VNTR-rs6323 3R-T haplotype (p = .007) in male probands. Family-based analysis showed significant preferential transmission of Dopamine receptor D4 exon 3 VNTR-rs1800955 7R-T haplotype from parents to male probands (p = .008). Interaction between DBH gene variants and low enzymatic activity was also noticed, especially in male probands. Conclusion: Data obtained may partly answer the male biasness of ADHD.

Interactions Between Early Trauma and Catechol-O-Methyltransferase Genes on Inhibitory Deficits in Children With ADHD

Objective: To investigate the interaction between childhood trauma exposure with the catechol-O-methyltransferase (COMT) and dopamine receptor D4 (DRD4) polymorphisms in relation to neuropsychological measures in children with ADHD. Method: A cross-sectional examination of early traumatic experiences and the continuous performance test (CPT) were performed in 55 children with ADHD. Participants were also genotyped for the DRD4 exon III 48-bp variable number of tandem repeats (VNTR) polymorphism and the COMT Val158-Met (rs4680) polymorphism. Results: There was significant interaction between the effects of the COMT genotype and trauma in commission errors. In participants with ADHD carrying the COMT Val/Val genotype, the group exposed to trauma showed significantly higher commission errors than the non-traumatized group. However, for the participants with other genotypes, no significant differences were found. Conclusion: This study suggests that there exists a genetic influence on the association between childhood trauma and the severity of inhibitory deficits in children with ADHD.

Self-Reported Sexual Behavioral Interests and Polymorphisms in the Dopamine Receptor D4 (DRD4) Exon III VNTR in Heterosexual Young Adults.

Polymorphisms in the dopamine D4 receptor (DRD4) have previously been shown to associate with a variety of human behavioral phenotypes, including ADHD pathology, alcohol and tobacco craving, financial risk-taking in males, and broader personality traits such as novelty seeking. Recent research has linked the presence of a 7-repeat (7R) allele in a 48-bp variable number of tandem repeats (VNTR) along exon III of DRD4 to age at first sexual intercourse, sexual desire, arousal and function, and infidelity and promiscuity. We hypothesized that carriers of longer DRD4 alleles may report interest in a wider variety of sexual behaviors and experiences than noncarriers. Participants completed a 37-item questionnaire measuring sexual interests as well as Cloninger's Temperament and Character Inventory, and were genotyped for the 48-bp VNTR on exon III of DRD4. Based on our final genotyped sample of female (n=139) and male (n=115) participants, we found that 7R carriers reported interest in a wider variety of sexual behaviors (r=0.16) within a young adult heterosexual sample of European descent. To our knowledge, this is the first reported association between DRD4 exon III VNTR genotype and interest in a variety of sexual behaviors. We discuss these findings within the context of DRD4 research and broader trends in human evolutionary history.

Retraction Note to: Association of Catechol-O-methyltransferase val/met polymorphism with cognitive function in Gilles de la Tourette syndrome patients.

Gilles de la Tourette syndrome (GTS) is a kind of neuropsychiatric disorder with childhood onset. The cognitive dysfunction caused by GTS could affect the growth and learning of children and adolescents. The mechanism of cognitive functions was associated with dopaminergic system, thus we access the associations between polymorphism of some dopaminergic system-related genes including Catechol-O-methyltransferase (COMT) met/val, Dopamine receptor D4 (DRD4) exon III 48 bp VNTR (variable number of tandem repeats), Interleukin 1 (IL-1) Ra 86 bp and IL-1β exon 5, and cognitive functions in GTS patients. Genotyping analysis was performed through polymerase chain reaction (PCR). Test for cognitive functions of GTS patients included modified wisconsin card sorting test (WCST), trail making test, visual reproduction test, stroop test and verbal fluency test. The patients with COMT met/met genotype showed less perseverative errors in modified WCST test compared with patients with COMT val/val genotype (P < 0.05). Meanwhile, patients without allele val had better delayed memory in visual reproduction test, less errors in the stroop test and less perseverative errors in modified WCST test compared with patients with allele val (P < 0.05). However, no significant difference was found in cognitive functions among patients with different genotypes or alleles of polymorphisms of DRD4 exon III 48 bp VNTR, IL-1 Ra 86 bp and IL-1β exon 5 (P > 0.05). Polymorphism of COMT met/val was correlated with cognitive functions in GTS patients. This study provided basis for the analysis of molecular genetic pathology of cognitive dysfunctions in GTS.

Possible association of the DRD4 gene with a history of attention‐deficit/hyperactivity disorder in women with bulimia nervosa

Up to one-third of patients with bulimia nervosa (BN) report a history of attention-deficit/hyperactivity disorder (ADHD) symptoms, and the dopaminergic genes, especially the dopamine receptor D4 (DRD4), have been associated independently with both binge eating and ADHD. The purpose of this study was to (1) compare the frequency of DRD4 exon III VNTR variants in 157 BN probands and equal number of healthy controls; (2) assess transmission of DRD4 alleles in 68 families of patients with BN; and (3) explore the possible role of DRD4 gene in childhood ADHD history in a subgroup of 81 women with BN. Our results showed that the BN probands and controls did not differ in DRD4 allele frequency. We also did not find evidence for preferential transmission of any DRD4 variant to the affected offspring with BN. However, the presence of either the 2-repeat or 7-repeat allele was associated with a history of childhood ADHD in BN (p = .038, odds ratio = 3.2). Our findings suggest that although DRD4 may not be associated with the diagnosis of BN, its variants are associated with a history of childhood ADHD in BN probands. This may have relevance for the understanding, prevention, and treatment of BN that evolves in the context of childhood ADHD.

Novelty‐seeking DRD4 polymorphisms are associated with human migration distance out‐of‐Africa after controlling for neutral population gene structure

Numerous lines of evidence suggest that Homo sapiens evolved as a distinct species in Africa by 150,000 years before the present (BP) and began major migrations out-of-Africa ∼50,000 BP. By 20,000 BP, our species had effectively colonized the entire Old World, and by 12,000 BP H. sapiens had a global distribution. We propose that this rapid migration into new habitats selected for individuals with low reactivity to novel stressors. Certain dopamine receptor D4 (DRD4) polymorphisms are associated with low neuronal reactivity and increased exploratory behavior, novelty seeking, and risk taking, collectively considered novelty-seeking trait (NS). One previous report (Chen et al.: Evol Hum Behav 20 (1999) 309-324) demonstrated a correlation between migratory distance and the seven-repeat (7R) VNTR DRD4 allele at exon 3 for human populations. This study, however, failed to account for neutral genetic processes (drift and admixture) that might create such a correlation in the absence of natural selection. Furthermore, additional loci surrounding DRD4 are now recognized to influence NS. Herein we account for neutral genetic structure by modeling the nonindependence of neutral allele frequencies between human populations. We retest the DRD4 exon 3 alleles, and also test two other loci near DRD4 that are associated with NS. We conclude there is an association between migratory distance and DRD4 exon 3 2R and 7R alleles that cannot be accounted for by neutral genetic processes alone.

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity

Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P=0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P=0.008 for total substitutions and P=0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.

Acute Intravenous Synaptamine Complex Variant KB220™ “Normalizes” Neurological Dysregulation in Patients during Protracted Abstinence from Alcohol and Opiates as Observed Using Quantitative Electroencephalographic and Genetic Analysis for Reward Polymorphisms: Part 1, Pilot Study with 2 Case Reports

It is well established that in both food- and drug-addicted individuals, there is dopamine resistance due to an association with the DRD2 gene A1 allele. Evidence is emerging whereby the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may find its place in recovery from reward deficiency syndrome (RDS) in patients addicted to psychoactive chemicals. Utilizing quantitative electroencephalography (qEEG) as an imaging tool, we show the impact of Synaptamine Complex Variant KB220™ as a putative activator of the mesolimbic system. We demonstrate for the first time that its intravenous administration reduces or “normalizes” aberrant electrophysiological parameters of the reward circuitry site. For this pilot study, we report that the qEEGs of an alcoholic and a heroin abuser with existing abnormalities (ie, widespread theta and widespread alpha activity, respectively) during protracted abstinence are significantly normalized by the administration of 1 intravenous dose of Synaptamine Complex Variant KB220™. Both patients were genotyped for a number of neurotransmitter reward genes to determine to what extent they carry putative dopaminergic risk alleles that may predispose them for alcohol or heroin dependence, respectively. The genes tested included the dopamine transporter (DAT1, locus symbol SLC6A3), dopamine D4 receptor exon 3 VNTR (DRD4), DRD2 TaqIA (rs1800497), COMT val158 met SNP (rs4680), monoamine oxidase A upstream VNTR (MAOA-uVNTR), and serotonin transporter-linked polymorphic region (5HTTLPR locus symbol SLC6A4). We emphasize that these are case studies, and it would be unlikely for all individuals to carry all putative risk alleles. Based on previous research and our qEEG studies (parts 1 and 2 of this study), we cautiously suggest that long-term activation of dopaminergic receptors (ie, DRD2 receptors) will result in their proliferation and lead to enhanced “dopamine sensitivity” and an increased sense of happiness, particularly in carriers of the DRD2 A1 allele. This is supported by a clinical trial on Synaptamine Complex Variant KB220™ using intravenous administration in > 600 alcoholic patients, resulting in significant reductions in RDS behaviors. It is also confirmed by the expanded oral study on Synaptose Complex KB220Z™, published as part 2 of this study. Future studies must await both functional magnetic resonance imaging and positron emission tomography scanning to determine the acute and chronic effects of oral KB220™ on numbers of D2 receptors and direct interaction at the nucleus accumbens. Confirmation of these results in large, population-based, case-controlled experiments is necessary. These studies would provide important information that could ultimately lead to significant improvement in recovery for those with RDS and dopamine deficiency as a result of a multiple neurotransmitter signal transduction breakdown in the brain reward cascade.

Dopamine D4 Receptor Exon III Polymorphism, Adverse Life Events and Personality Traits in a Nonclinical German Adult Sample

Personality and temperament embrace a wide area of both psychological and behavioral processes which are also based on disposition. A functional polymorphism in exon III of the dopamine D4 receptor gene (DRD4) has been a highly suspect genetic marker for personality in spite of ambiguous results. The present study aimed to further elucidate the relationship between DRD4, negative life events and personality in a representative nonclinical sample. Hundred sixty-seven Germans completed the NEO Five-Factor Inventory, the Tridimensional Personality Questionnaire and the California Adult Q-Sort. A factor analysis revealed 3 factors: emotional stability, social orientation and impulsivity. DNA from buccal cells was genotyped for the DRD4 variable-number tandem-repeat exon III polymorphism with respect to presence versus absence of the DRD4 7-repeat allele. Adverse life events were assessed by means of the Adverse Life Events Scale. Men carrying the DRD4 7-repeat allele were more impulsive than those without. Male 7-repeat carriers were more emotionally instable than others, but only when they experienced a large amount of negative life events. No genotype-personality relationships were found for women. The results indicate gender-specific influences of the DRD4 gene on human behavior and invite researchers to further investigate gene-environment correlations on personality traits.

Novelty Seeking: Interaction Between Parental Alcohol Use and Dopamine D4 Receptor Gene Exon III Polymorphism Over 17 Years

Recent meta-analyses have questioned the association between the dopamine receptor D4 (DRD4) gene polymorphism and the temperament trait of novelty seeking, and proposed an interaction between the polymorphism and other factors. We wanted to test whether parental alcohol use during childhood moderated the effect of an offspring dopamine receptor gene (DRD4) polymorphism on the temperament trait of novelty seeking in adulthood. A population-based sample of children and adolescents (n = 2149) and their parents was examined in 1980 and 1983 on parental alcohol use and rearing practices. In 1997, study participants completed the Temperament and Character Inventory for the novelty-seeking temperament trait, and a subsample (n = 150) was genotyped for the DRD4 exon III polymorphism. For the participants with the father, but not the mother, reporting more frequent alcohol consumption or drunkenness in examinations 17 and/or 14 years before the novelty-seeking assessment, an association between the short (two- or...

The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors

Thanks to the development of molecular genetics methods it is now possible to look for the genes which may contribute to posttraumatic stress disorder (PTSD). Polymorphism located in exon III of dopamine receptor type 4 (DRD4) gene was related to maladaptive stress responses as well as temperament traits related to PTSD. This study analyzed the association between the variable number tandem repeat (VNTR) DRD4 exon III polymorphism and intensity of PTSD symptoms in 107 (57 women and 50 men) survivors of a flood aged 14–62. Intensity of PTSD symptoms was measured using PTSD-F and PTSD-C questionnaires. Multivariate analysis of covariance (MANCOVA) was conducted to test the main and interactive effects of genotype and level of trauma exposure. Participants with at least one copy of the DRD4 long allele (seven or eight repetitions) had more intense PTSD symptoms on the Avoidance/Numbing scale (Cohen's f = .22) and the Total Scale (Cohen's f = .2) of the PTSD-F than participants who did not have these alleles in genotype. The results must be treated with caution, however, due to methodological restrictions and they need to be replicated on a larger sample.

A dopamine D4 receptor exon 3 VNTR allele protecting against migraine without aura

As dopamine plays an important role in the pathophysiology of migraine and antimigraine drugs have an effect on the dopamine system, the objective of this study was to examine the dopamine D4 receptor gene for involvement in the cause of migraine. We tested a VNTR-polymorphism in the dopamine D4 receptor gene, the exon 3 VNTR, in a sample of 190 family trios each with a proband with childhood migraine by using transmission disequilibrium test tests. We found a trend for transmission distortion of this marker in migraine, with the common seven-repeat allele of the VNTR transmitted 58 times and not transmitted 82 times (global likelihood ratio score (LRS) = 12.27, degress of freedom (DF) = 6, p = 0.06; for the 7-repeat allele: chi(2) = 5.1, p = 0.02). This effect came only from migraine without aura (145 trios), with the common 7-repeat allele transmitted 45 times and not transmitted 69 times (global LRS = 15.18; DF = 6, p = 0.019; for the 7-repeat allele: chi(2) = 6.4, p = 0.01; odds ratio, 0.47), whereas in migraine with aura (45 trios) there was no transmission distortion of the 7-repeat allele. We conclude that seven-repeat allele of the dopamine D4 receptor VNTR is a protective factor for migraine without aura. Because migraine is a common disorder, this protective effect may have contributed to the positive selection acting on the dopamine D4 receptor exon 3 VNTR seven-repeat allele in recent human history. We speculate that dopamine function in the lateral parabrachial nucleus is involved in migraine without aura.

Personality, Dopamine Receptor D4 Exon III Polymorphisms, and Academic Achievement in Medical Students

This study investigated the relationships between genetic polymorphisms, personality traits, and academic achievement in medical school students. Study subjects were 220 1st-year medical students at Korea University Medical School during two consecutive academic years (2003–2004). Grade-point averages (GPA) during the second semester of the 1st year of the medical school were obtained as a measure of academic achievement. In addition, all participants completed the Temperament and Character Inventory and questionnaires on depression and anxiety. The polymorphisms in exon III of the dopamine D4 receptor (DRD4) were determined using the polymerase chain reaction. Our results revealed that both male and female subjects with a higher GPA may be characterized as having higher persistence and lower novelty seeking traits. In addition, male subjects with high GPA had higher scores in self directedness and female subjects with a higher GPA may be characterized as having higher scores in harm avoidance. Male students with 4-repeat alleles had a significantly lower GPA than male students without 4-repeat alleles.This relationship also remained after controlling for the personality variables, none of which showed a relationship with the polymorphism after Bonferroni correction. For females, however, no associations could be found between GPA and the polymorphism. Thus, the present study demonstrated for the first time a possible influence of the DRD4 48 bp variable number of tandem repeats polymorphism on academic achievement and proved that this was not mediated by performance-associated personality traits.

Identification and Characterization of Tandem Repeats in Exon III of Dopamine Receptor D4 (DRD4) Genes from Different Mammalian Species

In this study we have identified and characterized dopamine receptor D4 (DRD4) exon III tandem repeats in 33 public available nucleotide sequences from different mammalian species. We found that the tandem repeat in canids could be described in a novel and simple way, namely, as a structure composed of 15- and 12- bp modules. Tandem repeats composed of 18-bp modules were found in sequences from the horse, zebra, onager, and donkey, Asiatic bear, polar bear, common raccoon, dolphin, harbor porpoise, and domestic cat. Several of these sequences have been analyzed previously without a tandem repeat being found. In the domestic cow and gray seal we identified tandem repeats composed of 36-bp modules, each consisting of two closely related 18-bp basic units. A tandem repeat consisting of 9-bp modules was identified in sequences from mink and ferret. In the European otter we detected an 18-bp tandem repeat, while a tandem repeat consisting of 27-bp modules was identified in a sequence from European badger. Both these tandem repeats were composed of 9-bp basic units, which were closely related with the 9-bp repeat modules identified in the mink and ferret. Tandem repeats could not be identified in sequences from rodents. All tandem repeats possessed a high GC content with a strong bias for C. On phylogenetic analysis of the tandem repeats evolutionary related species were clustered into the same groups. The degree of conservation of the tandem repeats varied significantly between species. The deduced amino acid sequences of most of the tandem repeats exhibited a high propensity for disorder. This was also the case with an amino acid sequence of the human DRD4 exon III tandem repeat, which was included in the study for comparative purposes. We identified proline-containing motifs for SH3 and WW domain binding proteins, potential phosphorylation sites, PDZ domain binding motifs, and FHA domain binding motifs in the amino acid sequences of the tandem repeats. The numbers of potential functional sites varied pronouncedly between species. Our observations provide a platform for future studies of the architecture and evolution of the DRD4 exon III tandem repeat, and they suggest that differences in the structure of this tandem repeat contribute to specialization and generation of diversity in receptor function.

Socio-demographic characteristics moderate the association between DRD4 and Novelty seeking

The association between dopamine receptor D4 (DRD4) gene polymorphism and the temperament dimension of Novelty seeking (NS) has recently been questioned. We tested whether childhood socio-demographic characteristics moderated this association. A population-based sample of children ( n = 2149) and their parents was analyzed in 1980 in terms of socio-economic circumstances and residential setting. In 1997, the NS temperament was measured, and subjects in the low and high ends of the distribution ( n = 150) were genotyped for DRD4 exon III polymorphism. An association between two- or five-repeat alleles of the DRD4 polymorphism and high NS scores was observed in the subjects with higher educated mothers, a higher annual household income, and living in an urban residential setting (OR’s ⩾ 3.9, 95% CI’s = 1.45–27.3) 17 years prior to the NS assessment. These findings were not explained by gender, age, or proximal process of child-rearing that, according to a prior report, have been shown to moderate the association. Socio-demographic characteristics did not moderate the association between the DRD4 seven-repeat allele and NS. These results provide further evidence of gene–environment interaction in NS, and suggest that environmental characteristics in the childhood may moderate the association between DRD4 polymorphisms and NS.

Novelty seeking: interaction between parental alcohol use and dopamine D4 receptor gene exon III polymorphism over 17 years

Recent meta-analyses have questioned the association between the dopamine receptor D4 (DRD4) gene polymorphism and the temperament trait of novelty seeking, and proposed an interaction between the polymorphism and other factors. We wanted to test whether parental alcohol use during childhood moderated the effect of an offspring dopamine receptor gene (DRD4) polymorphism on the temperament trait of novelty seeking in adulthood. A population-based sample of children and adolescents (n=2149) and their parents was examined in 1980 and 1983 on parental alcohol use and rearing practices. In 1997, study participants completed the Temperament and Character Inventory for the novelty-seeking temperament trait, and a subsample (n=150) was genotyped for the DRD4 exon III polymorphism. For the participants with the father, but not the mother, reporting more frequent alcohol consumption or drunkenness in examinations 17 and/or 14 years before the novelty-seeking assessment, an association between the short (two- or five-repeat) alleles of the DRD4 gene and extremely high novelty-seeking scores was observed. When the father reported less frequent alcohol consumption or drunkenness, the genotype was not associated with novelty seeking. The association remained after controlling for sex, age, and maternal child-rearing. These results provide preliminary information on gene-environment interaction on the temperament trait of novelty seeking and may partly explain the heterogeneity of findings concerning the association between DRD4 polymorphisms and novelty seeking.

Erratum: An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits

Correction to: Molecular Psychiatry (2004) 9, 730–731, doi:10.1038/mp.4001506. Following publication of the above paper, the author has identified an error with the names of the authors attributed. The correct author names are above.

Erratum: An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits

Erratum: An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits

Polymorphism of dopamine receptor D4 exon I corresponding region in chicken.

In stockbreeding, there are indications that behavioral traits of livestock have an effect on breeding and production. If the variation in individual behavior is related to that in neurotransmitter-related genes such as in humans, it would be possible to breed pedigrees composed of individuals having behavioral traits that are useful to production and breeding using selection based on genotypes. In this study, we investigated the exon I region of dopamine receptor D4 (DRD4), in which variation is related to psychiatric disorder in humans, in major poultry species namely Japanese quail (Coturnix japonica), chicken (Gallus gallus), ring-necked pheasant (Phasianus colchicus) and helmeted guinea fowl (Numida meleagris). Furthermore, we investigated Japanese cormorant (Phalacrocorax capillatus) and Japanese jungle crow (Corvus macrorhynchos) as an out-group. In these species of birds, the repeat of proline was identified in the region corresponding to the human polymorphic region. The repeat number was 9 in Japanese quail, ring-necked pheasant and Japanese cormorant; 12 in helmeted guinea fowl; and 3 in Japanese jungle crow. However, no polymorphism was found in these species. In contrast, polymorphism was observed in chicken and two alleles with 8 and 9 repeats were identified. Although 9 repeats (allele 9) were predominant in most chicken breeds, Black Minorca had only 8 repeats (allele 8). Intra-breed polymorphism was found in 6 out of 12 breeds, and two alleles (alleles 8 and 9) were detected in these breeds. This polymorphism, which is the first to be reported on a neurotransmitter-related gene in birds, would contribute significant information for elucidation of differences in behavioral traits in chicken breeds.