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The Chemistry of the Brain
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
As with serotonin, the dopaminergic system is controlled by a number of genes, some of which have polymorphisms that have been suggested as candidate genes for antisocial behavior. For example, DAT-1 variable number tandem repeat (VNTR) functional polymorphism is responsible for expressing the dopamine transporter protein, which controls dopamine levels in the synapses by reuptaking dopamine and releasing it into the presynaptic terminal.40 Different polymorphisms or alleles result in differing expression of the dopamine transporter, meaning that different alleles result in greater or lesser efficiency of the protein, hence affecting dopamine levels.
A Survey of Newer Gene Probing Techniques
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Single-locus probes can be produced by cloning DNA of interest. They have been used in the early stages of human genome mapping. Likewise, oligonucleotide probes corresponding to the consensus sequences of the tandem repeats of various hypervariable loci have been constructed. Such VNTR probes, each derived from a single locus, have been used to identify a large number of polymorphisms spanning the entire human genome.
DNA Analysis
Published in Steven H. Y. Wong, Iraving Sunshine, Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Victor W. Weedn, Demris A. Lee, Rhonda K. Roby, Mitchell M. Holland
STR tandem arrays are generally much smaller than LTRs, with a mean length on the order of 200 bp. There are more than 30,000 separate STR loci in the human genome. STRs have many of the same properties as RFLP VNTR loci, including high heterozygosity. However, because they are shorter, they can be discretely analyzed on acrylamide gels to the resolution of a single repeat unit, or single nucleotide base. Their small size makes them less susceptible to allelic dropout or preferential amplification. This greatly enhances the utility of STR analysis for degraded samples. STR analysis is easier to perform in combined sets and on automated instrumentation. With sufficient numbers of STR systems, discriminatory powers similar to current RFLP testing can be achieved.
Reducing risk in thiopurine therapy
Published in Xenobiotica, 2020
Anthony M. Marinaki, Monica Arenas-Hernandez
Variable number tandem repeats in the TPMT promoter region have been postulated to modulate TPMT expression and hence activity. The VNTR consist of A, B and C elements which differ in size and sequence. A single C element is present with varying numbers of A and B elements. An inverse correlation between the total number of VNTR repeat elements and TPMT activity has been reported in vitro but in vivo studies showed this effect to be not significant (Spire-Vayron de la Moureyre et al., 1999). Subsequent studies reported lower TPMT activity levels were associated with genotypes that included an allele with more than 5 repeat elements (Yan et al., 2000) and that three B repeats was the likely motif influencing reduced gene expression (Alves et al., 2001). These associations may be partly explained by disequilibrium between VNTR*6b and the coding region variant TPMT*3A which is associated with reduced TPMT activity and TPMT promoter VNTR were considered unlikely to be of clinical significance (Marinaki et al., 2003). A trinucleotide repeat 327 bp upstream of the TPMT transcription start site has been associated with increased TPMT activity, with (GCC)7 and (GCC)5 repeats associated with ultra-high TPMT activity in vivo and in reporter gene assays when compared to (GCC)6 (Roberts et al., 2008).
Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals
Published in The World Journal of Biological Psychiatry, 2019
Dimitry A. Chistiakov, Vladimir P. Chekhonin
In humans, a functionally relevant VNTR is located in the MAOA promoter. MAOA is an oxidase involved in oxidative deamination (i.e., degradation) of a number of important neurotransmitters, such as serotonin, dopamine and norepinephrine (Levitt et al. 1997). The MAOA-VNTR contains 30-bp long repeats, of which alleles with 2, 3.5 and 4 repeats are associated with higher enzyme activity and expression, whereas alleles 3 and 5 have lower MAOA activity. Individuals with VNTR alleles associated with increased MAOA activity (especially carriers of allele 2) were shown to exhibit highly aggressive behaviour and criminality (Guo et al. 2008; Beaver et al. 2013). Caspi et al. (2002) showed that maltreated children who have highly active VNTR alleles were more prone to develop violent behaviour in the future compared with carriers of low-active alleles. This observation indeed showed that the polymorphic MAOA region influences the effect of childhood maltreatment. Further attempts to replicate these findings resulted in the generation of conflicting results. However, in a meta-analysis, a moderating role of MAOA-VNTR in antisocial behaviour was confirmed in males, while this role was less evident in females (Byrd & Manuck 2014).
Genotypic diversity of Mycobacterium tuberculosis isolates from North-Central Indian population
Published in Pathogens and Global Health, 2019
Ravi Prakash, Rahul Gupta, Pragya Sharma, Sanjay Jain, Devendra Singh Chauhan, Vishwa Mohan Katoch, Pramod Kumar Tiwari
The present investigation revealed predominance of EAI3_IND/SIT11 genotype in Sahariya tribe followed by CAS1_Delhi/SIT26 genotype. The EAI_IND/SIT11 genotype was observed to have a greater number of MDR-TB cases as well as increased transmission links associated with familial and geographical settings in Sahariya tribe, which is a major concern. The use of MIRU-VNTRs along with spoligotyping was found to be more beneficial in discriminating MTB genotypes. Therefore, the establishment of suitable local VNTR combination as per the characteristics of the local circulating clinical strains might be needed in this population or geographical location. This will increase the resolution power as well as helping to identifying/correlating the transmission events. The use of whole genome sequencing and single colony cultures of strains in such populations or geographical settings will also play an important role in identifying the contact cases as well as transmission events with more accuracy in the near future. Hence, the information generated will be beneficial for future investigations and in evaluating the performance of TB control programmes in this region.