Genetics and deoxyribonucleic acid-based technology in clinical biochemistry
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
The two DNA strands are complementary, so that C on one strand bonds by hydrogen bonds with G on another strand and A pairs with T. These bases are always numbered from the 5′ to the 3′, with letters indicating the nucleotide bases. Genetic material can copy itself (replication) during the S phase of the cell cycle. DNA polymerase needs a pre-existing DNA template and moves along the two strands and adds the appropriate nucleotides, following the base pairing rules, to the growing chain. Two new double strands of DNA are formed, identical to the original double strand and the strands are anti-parallel. DNA polymerase always moves from 3′ to 5′ along the template strand, i.e. the reverse of the newly forming strand. Variable number tandem repeats (VNTR) are short and repetitive repeats distributed throughout the genome and that are grouped near telomeres.
Mycobacterium
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
Another important source of variation in mycobacteria is repeat sequences. Variable number of tandem repeat (VNTR) is based on the analysis of DNA segments containing tandem repeated sequences in which the number of copies of the repeated sequence varies among strains. These repeats are 15–100 bp long and dispersed at multiple locations in the genome sequence [76]. Mycobacterial Interspersed Repetitive Units (MIRUs) are a particular case of VNTR. They are intergenic regions and are reported as 12-character designations, each character corresponding to the number of repeats at one of the 12 MIRU loci. Short-sequence repeats (SSRs) are 2–5 bp long tandem repeats and are also present in mycobacteria. All of these repeat sequences have been extensively used for typing [77–79] and also for inferring epidemiologic issues of Mycobacterium isolates [80].
Genotyping and Its Implications for Transmission Dynamics and Tuberculosis Control
Peter D O Davies, Stephen B Gordon, Geraint Davies in Clinical Tuberculosis, 2014
VNTR typing is a PCR-based method that detects the number of tandem repeats at multiple loci in the genome by using locus-specific primers. The sizes of the repeat sequences are known, and so the number of repeats at each locus can be determined by the size of the resulting amplicons; for example, if the repeat sequence is 50 bp and the amplicon is 100 bp, then there are two repeats (Figure 4.3). Amplicon sizes can be visualised either on an agarose gel by electrophoresis or on a DNA sequencer, and the number of repeats at each locus are compared between strains [2]. In the late 1990s, Frothingham and Meeker-O’Connell [19] identified five exact tandem repeat loci (ETR A-E) and Supply et al. [20] identified 41 MIRU-VNTR loci, 12 of which were initially chosen for genotyping purposes. The discriminatory power of MIRU-VNTR increases in proportion to the number of loci that are included [21–23]. The recently proposed international standard now includes 24 MIRU-VNTR loci [21], and this has been implemented prospectively for use in public health in the United States [18,24], the Netherlands and the United Kingdom [25].
Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with Peripheral Neuropathy
Published in Immunological Investigations, 2018
Monika Buraczynska, Kinga Buraczynska, Pawel Zukowski, Andrzej Ksiazek
The human IL-4 gene maps to the long arm of chromosome 5 (5q31–33), where it is located within the cluster of other Th2 cytokine genes (Le Beau et al., 1989; Marsh et al., 1994). Several polymorphisms in the IL-4 gene have been described; some of them implicated in the regulation of the IL-4 production. An important frequent variant is a variable number tandem repeat (VNTR) of 70 bp polymorphism located in the third intron (Mout et al., 1991). Two alleles were observed: one with a 70 bp deletion (183 bp) and one with a 70 bp insertion (253 bp) (Vandenbroeck et al., 1997). The VNTR polymorphism of the IL-4 gene has been reported to be associated with a number of inflammatory diseases (Basol et al., 2014; Sobti et al., 2010; Tong et al., 2013; Vandenbroeck and Goris, 2003). Recently, the results of a Turkish study suggested that the VNTR polymorphism in the IL-4 gene plays an important role in DPN (Basol et al., 2013).
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).
Genotyping comparison of Mycobacterium leprae isolates by VNTR analysis from nasal samples in a Brazilian endemic region
Published in Pathogens and Global Health, 2018
Luana Nepomueceno Costa Lima, Cristiane Cunha Frota, Phillip Noel Suffys, Amanda Nogueira Brum Fontes, Rosa Maria Salani Mota, Rosa Livia Freitas Almeida, Maria Araci de Andrade Pontes, Heitor de Sá Gonçalves, Carl Kendall, Ligia Regina Sansigolo Kerr
The conventional epidemiology of leprosy has be improved by strain genotyping tools. The isolates differentiation approach using molecular markers are useful to distinguish different strains of the leprosy bacilli. Variable number tandem repeat (VNTR) provides data about the pattern of variation in the Mycobacterium leprae genome [3–5]. The VNTR typing tool is based on the number of repetitive sequences in polymorphic micro- and mini-satellite regions of the bacteria [6]. Some polymorphic loci are suitable for identifying genotypes according to the discriminatory capacity, stability, and reproducibility. There is considerably more variation in repeat numbers at VNTR locus than in non-repetitive DNA sequences, because length-altering mutations due to slipped-strand mispairing occur at a much higher rate than the inherent DNA substitution or mutation frequency of DNA polymerase [7,8].
Related Knowledge Centers
- Allele
- DNA Profiling
- Genome
- Heredity
- Tandem Repeat
- Nucleic Acid Sequence
- Chromosome
- Genetics
- Forensic Science
- Genetic Recombination