The role of the SLC6A3 3’ UTR VNTR in nicotine effects on cognitive, affective, and motor function

Abstract Rationale Nicotine has been widely studied for its pro-dopaminergic effects. However, at the behavioural level, past investigations have yielded heterogeneous results concerning effects on cognitive, affective, and motor outcomes, possibly linked to individual differences at the level of genetics. A candidate polymorphism is the 40-base-pair variable number of tandem repeats polymorphism (rs28363170) in the SLC6A3 gene coding for the dopamine transporter (DAT). The polymorphism has been associated with striatal DAT availability (9R-carriers > 10R-homozygotes), and 9R-carriers have been shown to react more strongly to dopamine agonistic pharmacological challenges than 10R-homozygotes. Objectives In this preregistered study, we hypothesized that 9R-carriers would be more responsive to nicotine due to genotype-related differences in DAT availability and resulting dopamine activity. Methods N=194 non-smokers were grouped according to their genotype (9R-carriers, 10R-homozygotes) and received either 2-mg nicotine or placebo gum in a between-subject design. Spontaneous blink rate (SBR) was obtained as an indirect measure of striatal dopamine activity and smooth pursuit, stop signal, simple choice and affective processing tasks were carried out in randomized order. Results Reaction times were decreased under nicotine compared to placebo in the simple choice and stop signal tasks, but nicotine and genotype had no effects on any of the other task outcomes. Conditional process analyses testing the mediating effect of SBR on performance and how this is affected by genotype yielded no significant results. Conclusions Overall, we could not confirm our main hypothesis. Individual differences in nicotine response could not be explained by rs28363170 genotype.

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Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.1360 ◽

2015 ◽

Vol 282 (1813) ◽

pp. 20151360

Author(s):

Richard P. Ebstein ◽

Mikhail V. Monakhov ◽

Yunfeng Lu ◽

Yushi Jiang ◽

Poh San Lai ◽

...

Keyword(s):

Individual Differences ◽

Tandem Repeats ◽

Political Attitudes ◽

Receptor Gene ◽

Variable Number ◽

Han Chinese ◽

Political Attitude ◽

Dopamine D4 Receptor ◽

The Social ◽

D4 Receptor

Twin and family studies suggest that political attitudes are partially determined by an individual's genotype. The dopamine D4 receptor gene ( DRD4 ) exon III repeat region that has been extensively studied in connection with human behaviour, is a plausible candidate to contribute to individual differences in political attitudes. A first United States study provisionally identified this gene with political attitude along a liberal–conservative axis albeit contingent upon number of friends. In a large sample of 1771 Han Chinese university students in Singapore, we observed a significant main effect of association between the DRD4 exon III variable number of tandem repeats and political attitude. Subjects with two copies of the 4-repeat allele (4R/4R) were significantly more conservative. Our results provided evidence for a role of the DRD4 gene variants in contributing to individual differences in political attitude particularly in females and more generally suggested that associations between individual genes, and neurochemical pathways, contributing to traits relevant to the social sciences can be provisionally identified.

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Genetic linkage of Kozak sequence polymorphism of the platelet glycoprotein Ibalpha with human platelet antigen-2 and variable number of tandem repeats polymorphism, and its relationship with coronary artery disease

British Journal of Haematology ◽

10.1046/j.1365-2141.2000.02479.x ◽

2000 ◽

Vol 111 (4) ◽

pp. 1247-1249 ◽

Cited By ~ 22

Author(s):

Fumihiro Ishida ◽

Toshiro Ito ◽

Manabu Takei ◽

Shigetaka Shimodaira ◽

Kiyoshi Kitano ◽

...

Keyword(s):

Genetic Linkage ◽

Tandem Repeats ◽

Human Platelet ◽

Variable Number ◽

Sequence Polymorphism ◽

Platelet Glycoprotein ◽

Kozak Sequence ◽

Platelet Antigen ◽

Human Platelet Antigen ◽

Artery Disease

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Rapid Serial Auditory Presentation

Experimental Psychology (formerly Zeitschrift für Experimentelle Psychologie) ◽

10.1027/1618-3169/a000295 ◽

2015 ◽

Vol 62 (5) ◽

pp. 346-351 ◽

Cited By ~ 15

Author(s):

Ana Franco ◽

Julia Eberlen ◽

Arnaud Destrebecqz ◽

Axel Cleeremans ◽

Julie Bertels

Keyword(s):

Statistical Learning ◽

Reaction Times ◽

Visual Presentation ◽

Detection Task ◽

Speech Segmentation ◽

Auditory Presentation ◽

Indirect Measure ◽

Speech Stream ◽

Adult Participants ◽

Presentation Procedure

Abstract. The Rapid Serial Visual Presentation procedure is a method widely used in visual perception research. In this paper we propose an adaptation of this method which can be used with auditory material and enables assessment of statistical learning in speech segmentation. Adult participants were exposed to an artificial speech stream composed of statistically defined trisyllabic nonsense words. They were subsequently instructed to perform a detection task in a Rapid Serial Auditory Presentation (RSAP) stream in which they had to detect a syllable in a short speech stream. Results showed that reaction times varied as a function of the statistical predictability of the syllable: second and third syllables of each word were responded to faster than first syllables. This result suggests that the RSAP procedure provides a reliable and sensitive indirect measure of auditory statistical learning.

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Quantitative evaluation of post-bone marrow transplant engraftment status using fluorescent-labeled variable number of tandem repeats

Molecular Diagnosis ◽

10.1054/xd.2000.7436 ◽

2000 ◽

Vol 05 (2) ◽

pp. 129-138

Author(s):

Robert A. Luhm ◽

Daniel B. Bellissimo ◽

Arejas J. Uzgiris ◽

William R. Drobyski ◽

Martin J. Hessner

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplant ◽

Quantitative Evaluation ◽

Tandem Repeats ◽

Marrow Transplant ◽

Variable Number

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Faculty Opinions recommendation of Both polymorphic variable number of tandem repeats and autoimmune regulator modulate differential expression of insulin in human thymic epithelial cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7921958.8280057 ◽

2011 ◽

Author(s):

David Serreze

Keyword(s):

Epithelial Cells ◽

Differential Expression ◽

Tandem Repeats ◽

Variable Number ◽

Thymic Epithelial Cells ◽

Autoimmune Regulator

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Dopaminergic Genes Polymorphisms and Prefrontal Cortex Efficiency Among Obese People - Whether Gender is a Differentiating Factor?

Current Molecular Medicine ◽

10.2174/1566524019666190424143653 ◽

2019 ◽

Vol 19 (6) ◽

pp. 405-418

Author(s):

Maciej Bieliński ◽

Natalia Lesiewska ◽

Roman Junik ◽

Anna Kamińska ◽

Andrzej Tretyn ◽

...

Keyword(s):

Prefrontal Cortex ◽

Executive Functions ◽

Tandem Repeats ◽

Wisconsin Card Sorting Test ◽

Variable Number ◽

Card Sorting ◽

Obese People ◽

Perseverative Errors ◽

Wisconsin Card Sorting ◽

Sorting Test

Background:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of tandem repeats - VNTR) and WCST parameters to investigate the functions of the frontal lobes in obese individuals.Objective:To find the significant correlations between polymorphisms of DAT1, COMTVal158Met, DRD4 and executive functions in obese subjects.Methods:The analysis of the frequency of individual alleles was performed in 248 obese patients (179 women, 69 men). Evaluation of the prefrontal cortex function (operating memory and executive functions) was measured with the Wisconsin Card Sorting Test (WCST). Separate analyzes were performed in age subgroups to determine different activities and regulation of genes in younger and older participants.Results:Scores of WCST parameters were different in the subgroups of women and men and in the age subgroups. Regarding the COMT gene, patients with A/A and G/A polymorphisms showed significantly better WCST results in WCST_P, WCST_CC and WCST_1st. Regarding DAT1 men with L/L and L/S made less non-perseverative errors, which was statistically significant. In DRD4, significantly better WCST_1st results were found only in older women with S allele.Conclusion:Obtained results indicate the involvement of dopaminergic transmission in the regulation of prefrontal cortex function. Data analysis indicates that prefrontal cortex function may ensue, from different elements such as genetic factors, metabolic aspects of obesity, and hormonal activity (estrogen).

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Cortical silent period reflects individual differences in action stopping performance

Scientific Reports ◽

10.1038/s41598-021-94494-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mario Paci ◽

Giulio Di Cosmo ◽

Mauro Gianni Perrucci ◽

Francesca Ferri ◽

Marcello Costantini

Keyword(s):

Individual Differences ◽

Response Inhibition ◽

Primary Motor Cortex ◽

Silent Period ◽

Intracortical Inhibition ◽

Stop Signal ◽

Stop Signal Task ◽

Behavioral Differences ◽

Cortical Silent Period ◽

Stop Signal Reaction Time

AbstractInhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

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Molecular characteristics of Brucella melitensis isolates from humans in Qinghai Province, China

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00829-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Zhi-Jun Zhao ◽

Ji-Quan Li ◽

Li Ma ◽

Hong-Mei Xue ◽

Xu-Xin Yang ◽

...

Keyword(s):

Tandem Repeats ◽

Brucella Melitensis ◽

Draft Genome ◽

Geographic Origin ◽

Variable Number ◽

Human Brucellosis ◽

Molecular Characteristics ◽

Whole Genome ◽

Qinghai Province ◽

Variable Number Tandem Repeats

Abstract Background The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly, with confirmed cases distributed across 31 counties. However, the epidemiology of brucellosis transmission has not been fully elucidated. To characterize the infecting strains isolated from humans, multiple-locus variable-number tandem repeats analysis (MLVA) and whole-genome single-nucleotide polymorphism (SNP)-based approaches were employed. Methods Strains were isolated from two males blood cultures that were confirmed Brucella melitensis positive following biotyping and MLVA. Genomic DNA was extracted from these two strains, and whole-genome sequencing was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases. Results The two Brucella isolates were identified as B. melitensis biovar 3 (QH2019001 and QH2019005) following conventional biotyping and were found to have differences in their variable number tandem repeats (VNTRs) using MLVA-16. Phylogenetic examination assigned the 96 strains to five genotype groups, with QH2019001 and QH2019005 assigned to the same group, but different subgroups. Moreover, the QH2019005 strain was assigned to a new subgenotype, IIj, within genotype II. These findings were then combined to determine the geographic origin of the two Brucella strains. Conclusions Utilizing a whole-genome SNP-based approach enabled differences between the two B. melitensis strains to be more clearly resolved, and facilitated the elucidation of their different evolutionary histories. This approach also revealed that QH2019005 is a member of a new subgenotype (IIj) with an ancient origin in the eastern Mediterranean Sea.

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Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs

Nature Communications ◽

10.1038/s41467-021-24378-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Tsung-Yu Lu ◽

Katherine M. Munson ◽

Alexandra P. Lewis ◽

Qihui Zhu ◽

Luke J. Tallon ◽

...

Keyword(s):

Tandem Repeats ◽

Traditional Approach ◽

Variable Number Tandem Repeat ◽

Variable Number ◽

Population Diversity ◽

Protein Coding ◽

Short Reads ◽

Repeat Structure ◽

Continental Population ◽

Develop Software

AbstractVariable number tandem repeats (VNTRs) are composed of consecutive repetitive DNA with hypervariable repeat count and composition. They include protein coding sequences and associations with clinical disorders. It has been difficult to incorporate VNTR analysis in disease studies that use short-read sequencing because the traditional approach of mapping to the human reference is less effective for repetitive and divergent sequences. In this work, we solve VNTR mapping for short reads with a repeat-pangenome graph (RPGG), a data structure that encodes both the population diversity and repeat structure of VNTR loci from multiple haplotype-resolved assemblies. We develop software to build a RPGG, and use the RPGG to estimate VNTR composition with short reads. We use this to discover VNTRs with length stratified by continental population, and expression quantitative trait loci, indicating that RPGG analysis of VNTRs will be critical for future studies of diversity and disease.

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