Detection Of Single Nucleotide Polymorphisms Research Articles

Rapid detection of phenotypes Bombay sedel and nonsecretor rs200157007 SNP (302C\u2009>\u2009T) by real-time PCR-based methods

The sedel allele is one of the nonsecretor alleles (se) of FUT2 generated by an Alu-mediated recombination event and was first found in Indian Bombay phenotype individuals who have anti-H, anti-A, and anti-B antibodies in their serum. As well as anti-A, and anti-B antibodies, anti-H is clinically significant because it causes sever hemolytic transfusion reactions. Like sedel, se302 having a missense single nucleotide polymorphism (SNP), 302C > T, is characteristic of South Asians with a frequency of 10–30%. We developed a real-time PCR melting curve analysis for detection of sedel using a 127-bp amplicon encompassing the breakpoint junction. In addition, by performing duplex PCR by amplifying a 65-bp amplicon of the FUT2 coding region at the same time, we could determine the zygosity of sedel in a single tube. We also developed an Eprobe-mediated PCR assay (Eprobe-PCR) for detection of 302C > T of FUT2. These methods were validated by analyzing 58 Tamils and 54 Sinhalese in Sri Lanka. Both the duplex PCR melting curve analysis for determination of sedel zygosity and the Eprobe-PCR assay for detection of 302C > T exactly determined three genotypes. In addition, the results of the present methods were in complete agreement with those obtained by previously established methods. The two present methods were reliable and seem to be advantageous for large-scale association studies of FUT2 polymorphisms in South Asian populations.

A single nucleotide polymorphism electrochemical sensor based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probes.

Anultrasensitive electrochemical sensor has been constructedfor the detection of single nucleotide polymorphisms (SNPs) based on DNA-functionalized Cd-MOFs-74 as cascade signal amplification probe under enzyme-freeconditions. Interestingly, the introduction ofan auxiliary probe did not disturb the detection of SNP targets, but could bind more Cd-MOFs-74 signal elements to enhance thedifferent pulse voltammetry electrochemical signal 2~3 times as compared to sensing system without auxiliary probe, which obviously improves the sensitivity of the proposed sensor. Experimental results taking p53 tumor suppressor gene as SNP model demonstrated that the proposed method can be employed to sensitively and selectively detect target p53 gene fragment with a linear response ranging from 0.01 to 30 pmol/L (detection limit of 6.3 fmol/L) under enzyme-freeconditions. Utilizing this strategy, the ultrasensitive SNP electrochemical sensor is a promising tool for the determination of SNPs in biomedicine. Graphical Abstract.

Single Nucleotide Polymorphism Discovery and Genetic Differentiation Analysis of Geese Bred in Poland, Using Genotyping-by-Sequencing (GBS).

Poland is the largest European producer of goose, while goose breeding has become an essential and still increasing branch of the poultry industry. The most frequently bred goose is the White Kołuda® breed, constituting 95% of the country’s population, whereas geese of regional varieties are bred in smaller, conservation flocks. However, a goose’s genetic diversity is inaccurately explored, mainly because the advantages of the most commonly used tools are strongly limited in non-model organisms. One of the most accurate used markers for population genetics is single nucleotide polymorphisms (SNP). A highly efficient strategy for genome-wide SNP detection is genotyping-by-sequencing (GBS), which has been already widely applied in many organisms. This study attempts to use GBS in 12 conservative goose breeds and the White Kołuda® breed maintained in Poland. The GBS method allowed for the detection of 3833 common raw SNPs. Nevertheless, after filtering for read depth and alleles characters, we obtained the final markers panel used for a differentiation analysis that comprised 791 SNPs. These variants were located within 11 different genes, and one of the most diversified variants was associated with the EDAR gene, which is especially interesting as it participates in the plumage development, which plays a crucial role in goose breeding.

SNP Alleles Associated With Low Bolting Tendency in Sugar Beet.

The identification of efficient molecular markers related to low bolting tendency is a priority in sugar beet (Beta vulgaris L.) breeding. This study aimed to identify SNP markers associated with low bolting tendency by establishing a genome-wide association study. An elaborate 3-year field trial comprising 13 sugar beet lines identified L14 as the one exhibiting the lowest bolting tendency along with an increased survival rate after autumnal sowing. For SNP discovery following phenotyping, contrasting phenotypes of 24 non-bolting and 15 bolting plants of the L14 line were sequenced by restriction site-associated DNA sequencing (RAD-seq). An association model was established with a set of 10,924 RAD-based single nucleotide polymorphism (SNP) markers. The allelic status of the most significantly associated SNPs ranked based on their differential allelic status between contrasting phenotypes (p < 0.01) was confirmed on three different validation datasets comprising diverse sugar beet lines and varieties adopting a range of SNP detection technologies. This study has led to the identification of SNP_36780842 and SNP_48607347 linked to low bolting tendency and can be used for marker-assisted breeding and selection in sugar beet.

Association between LINC-PINT and LINC00599 gene polymorphism and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China

BackgroundSteroid-induced osteonecrosis of the femoral head (ONFH) is a complex disease affected by genetics. LncRNA LINC-PINT and LINC00599 have been proved to be associated with susceptibility to a variety of diseases, however it is not clear whether they are related to steroid-induced ONFH. Therefore, this study was aimed at investigating the correlation between the polymorphisms of LINC-PINT and LINC00599 genes and steroid-induced ONFH in the population of northern China. MethodsA case-control study including 199 patients and 725 controls was designed. The Agena MassARRAY platform was used for the detection of single nucleotide polymorphisms (SNPs) in LINC-PINT and LINC00599 genes. Chi-square test and logistic regression were used to evaluate the association between the above SNPs and steroid-induced ONFH in allelic and genetic models. Besides, one-way ANOVA was used to study the relationship between these SNPs and partial lipid levels. ResultsIn the LINC00599 gene, two sites are related to steroid-induced ONFH. Among them, rs2272026 increased the risk of the disease in co-dominant (heterozygous) and dominant models. And rs1962430 is a risk factor for this disease in the allelic, co-dominance (heterozygous), dominant and additive model. whereas in women with steroid-induced ONFH, three sites in the LINC-PINT gene are related to the disease. Thereinto, rs157916 reduces the risk of the disease in allelic, co-dominant (homozygous), recessive and additive models. Rs16873842 is related to the reduced risk of the disease in allele, dominant and additive models. And rs7781295 is a protective factor for steroid-induced ONFH in the allelic and additive model. ConclusionOur study suggests that the polymorphisms of LINC-PINT and LINC00599 genes are related to the susceptibility of steroid-induced ONFH in Chinese Han population.

TARDBP p.I383V, a recurrent alteration in Greek FTD patients

BackgroundA significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed to mutations in major genes such as GRN, MAPT and C9orf72. Our previous report on a Greek FTD cohort revealed the presence of the single nucleotide polymorphism (SNP) p.I383V (rs80356740) in the TARDBP gene in three unrelated patients. Our objective was to develop a novel, fast and accurate method for the detection of this particular SNP and evaluate the assay in a larger cohort. Methods and resultsA real-time qPCR-melting curve analysis method was developed, validated and tested in 142 FTD patients and 111 healthy control subjects. The SNP was detected in another two patients raising its yield in FTD patients to 3.5% (5 out of 142 patients) while one in 111 healthy controls was found to be a carrier. However, its frequency in the general population has been reported extremely low in international SNP databases (0.002%). ConclusionThis fact along with the indicated pathogenicity of this SNP in some bioinformatics tools, suggest that TARDBP p.I383V is recurrent and likely pathogenic for the Greek FTD population. Our high-throughput method could be used for genotyping in other larger patient cohorts and in other populations. Additionally, functional in vitro studies are required for the final adjudication of this TARDBP alteration as a pathogenic alteration.

Genetic association between NLRP3 gene and patients with acne vulgaris

Objective The aim was to investigate the genetic association between NACHT, LRR, and PYD Domains-Containing Protein 3 (NLRP3) gene and acne vulgaris among patients. Background Acne vulgaris is a common chronic skin disease. Inflammation is an important pathogenic mechanism of acne, and NLRP3 polymorphisms have been reported to be involved in the mediation and occurrence of the inflammation. However, only a few studies on NLRP3 and acne have been reported, and the mechanism remains unclear. Participants and methods To reach the goal of this research, a case–control study was designed. The study sample included 50 participants divided into two groups: patient group included 40 patients with acne vulgaris having comedones, papules, and nodules, and the control group included 10 healthy age-matched and sex-matched participants. All candidates were subjected to full history taking, clinical examination, BMI, and laboratory investigations for detection of NLRP3 gene single nucleotide polymorphism in DNA extracted from blood samples by real-time polymerase chain reaction. Results We found that taking CC genotype and C allele as references, NLRP3 CG, GG, and CG + GG genotypes and G allele showed significantly higher frequency in all cases compared with control groups (P = 0.030, 0.003, 0.004, and 0.001, respectively). Regarding severity, it was increased significantly in patients carrying CC, CG, and GG, respectively. Most of the severe cases had GG genotype (66.7%), whereas GG genotype was seen in moderate cases (17.6%). GG genotype was significantly associated with severe grades. Conclusion Our study suggests that the NLRP3 SNP rs10754558 is associated with the incidence of (atrioventricular) AV. The G allele might be a genetic risk factor for AV.

Detection of single nucleotide polymorphisms (SNPs) in a SARS-CoV-2 virus strain in Vietnam

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a pandemic of acute respiratory disease in humans. This pandemic has now spread worldwide and caused more than 2,000,000 deaths by 15 January 2021. The complexity and the ongoing pandemic of coronavirus SARS-CoV-2 make it difficult to control the disease. Sequence analysis on some open reading frames (ORFs) of a SARS-CoV-2 virus strain isolated in Vietnam in February 2020 (SARS-CoV-2/NIHE/human/2020/VIE strain) revealed some single nucleotide polymorphisms (SNPs) that only appeared in the Vietnamese strain in comparison to those of the isolates in other countries, including: (1) a change in ORF8-Nucleocapsid (accession number MT127114.1) at nucleotide (nt) 691 (CTC in SARS-CoV-2/NIHE/human/2020/VIE strain, TTC in all other isolates) but it does not change the encoded amino acid, (2) ORF3a-EM-ORF6-ORF7a region (accession number MT127115.1) has four-point changes, three of which lead to changes in the amino acid sequences, being nt 479 (GTA encoding Valine changed into TTA encoding Leucine), nt 575 (CGC encoding Arginine changed to GGC encoding Glycine) in the M gene, and nt 1126 (GTG encoding Valine changed to GAG encoding Glutamic acid) in ORF6. Taken together, the results provided useful information for the SARS-CoV-2 diagnostic kit and vaccine development.

Sensitive Detection of Single-Nucleotide Polymorphisms by Solid Nanopores Integrated With DNA Probed Nanoparticles.

Single-nucleotide polymorphisms (SNPs) are the abundant forms of genetic variations, which are closely associated with serious genetic and inherited diseases, even cancers. Here, a novel SNP detection assay has been developed for single-nucleotide discrimination by nanopore sensing platform with DNA probed Au nanoparticles as transport carriers. The SNP of p53 gene mutation in gastric cancer has been successfully detected in the femtomolar concentration by nanopore sensing. The robust biosensing strategy offers a way for solid nanopore sensors integrated with varied nanoparticles to achieve single-nucleotide distinction with high sensitivity and spatial resolution, which promises tremendous potential applications of nanopore sensing for early diagnosis and disease prevention in the near future.

A simple one-step PCR assay for SNP detection.

Polymerase Chain Reaction (PCR) is a powerful tool to detect natural variation or experimentally introduced variation in research and clinical settings and a widely-used method for genotyping. Single nucleotide polymorphisms (SNP) detection is challenging by PCR as the variant and wild type alleles differ by only one nucleotide. Traditional methods to detect SNPs, including Sanger sequencing and commercial kits, are usually time-consuming. Here we describe a simple primer design strategy that enables specific variant detection through regular one-step PCR. The strategy employs the differential efficiency of genomic PCR using a primer that has a single mismatch with the chromosome that contains the SNP to be detected (typically the variant allele) versus two mismatches with the corresponding alternative allele (typically the wild type allele). To date, we have successfully employed this approach to detect more than 20 SNPs. The simplicity and robustness of the approach allows rapid application to legacy mutations as well as newly discovered or generated SNPs.

ASSOCIATION BETWEEN POLYMORPHISMS IN CYTOKINE IL7 GENE AND CMV IN RENAL FAILURE PATIENTS IN DIYALA PROVINCE

Background: The human cytomegalovirus (HCMV) is an important human pathogen primarily affecting immunocompromised patients, like Renal failure patients, transplant recipients or HIV-infected individuals. Renal failure diesease is a wide dissemination among kidney patients in Ba'quba City. Aim: the study was carried out to detect the HCMV and detection of several single nucleotide polymorphisms (SNP) in IL7 among100 patient suffering from acute or chronic renal failure whom admitted to Ibn Sina Center for kidney Dialysis in Baquba Teaching Hospital. Patients and Methods: This study was conducted for the period from 1/12/2019 to 15/6/2020 in Baquba city in Iraq, with age ranged between (13-76) years. The samples were diagnosed by serological and molecular tests. Results: The obtained results showed that HCMV antibody was detected in renal failure patients by ELISA IgG (100%) while IgM were (15.0%) . Also, Distribution of genotypes for the (IL7) rs7007634 gene samples of renal failure patients 15 out of 20, Chi-Square (9.375) investigated samples (P value 0.002) . The alignment results of the 323 bp samples revealed the presence of one genetic variation variably distributed in some of the analyzed samples in comparison with the referring IL7 genetic sequences. Distribution of genotypes of the rs7007634(IL7)gene in renal failure patient samples according to CMV infection 12 sample infection in CMV and 3 sample without CMV.

Crosstalk of Cyclin-dependent kinase inhibitor 1A (CDKN1A) gene polymorphism with p53 and CCND1 polymorphism in breast cancer.

Mutations and polymorphisms in genes of cell- cycle and apoptosis regulatory pathway influence the breast cancer risk. Analysis of single low penetrance mutant alleles may not reflect the precise risk association when analyzed alone. A total of 115 DNA samples extracted from breast cancer patients and an equal number of age and sex-matched normal controls were used for polymorphic analysis. Genotyping for p21 rs1801270 and CCND1 rs603965 was done by PCR-RFLP method while AFLP method was used for p53 rs1042522 single nucleotide polymorphism detection. Statistical methods included simple mean±SD and correlation coefficient to analyze the risk of association of p21, p53 and CCND1 SNPs and breast cancer. Individuals harboring SNPs in p21, p53 and CCND1 genes namely rs1801270, rs1042522 and rs603965, respectively were rendered increasingly susceptible to developing breast cancer when compared with normal controls. Our report emphasizes the need of combinational analysis of low-penetrance mutant alleles to assess accurately their association with breast cancer risk. Future case-control studies analyzing gene-environment interactions across different populations may confirm reported risk associations of studied polymorphisms with developing breast cancer.

Application of Nanotechnology for Sensitive Detection of Low-Abundance Single-Nucleotide Variations in Genomic DNA: A Review.

Single-nucleotide polymorphisms (SNPs) are the simplest and most common type of DNA variations in the human genome. This class of attractive genetic markers, along with point mutations, have been associated with the risk of developing a wide range of diseases, including cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative diseases. Several existing methods to detect SNPs and mutations in body fluids have faced limitations. Therefore, there is a need to focus on developing noninvasive future polymerase chain reaction (PCR)–free tools to detect low-abundant SNPs in such specimens. The detection of small concentrations of SNPs in the presence of a large background of wild-type genes is the biggest hurdle. Hence, the screening and detection of SNPs need efficient and straightforward strategies. Suitable amplification methods are being explored to avoid high-throughput settings and laborious efforts. Therefore, currently, DNA sensing methods are being explored for the ultrasensitive detection of SNPs based on the concept of nanotechnology. Owing to their small size and improved surface area, nanomaterials hold the extensive capacity to be used as biosensors in the genotyping and highly sensitive recognition of single-base mismatch in the presence of incomparable wild-type DNA fragments. Different nanomaterials have been combined with imaging and sensing techniques and amplification methods to facilitate the less time-consuming and easy detection of SNPs in different diseases. This review aims to highlight some of the most recent findings on the aspects of nanotechnology-based SNP sensing methods used for the specific and ultrasensitive detection of low-concentration SNPs and rare mutations.

Functionalized Germanene-Based Nanomaterials for the Detection of Single Nucleotide Polymorphism

Functionalized Germanene-Based Nanomaterials for the Detection of Single Nucleotide Polymorphism

A visible and colorimetric nanobiosensor based on DNA-CuO nanoparticle for detection of single nucleotide polymorphism involved in sickle cell anemia disease

Sickle cell anemia (SCA) is a blood monogenic disease, which is caused by a single nucleotide mutation in the β-globin gene. In this work, to diagnose prenatal of the disease, a colorimetric nanobiosensor established using catalytic and peroxidase-like properties of copper oxide nanoparticle (CuO) and its interaction with DNA. It used to detect SNP in cell-free fetal DNA (cffDNA), as a promising diagnostic biomarker. The nanobiosensor detected the target sequence of the non-target, exactly even with one nucleotide polymorphism. The optimized method was capable of detecting the target sequence over its concentrations ranged from 2 nM to 12 nM (R2 = 0.96) with a detection limit of 0.64 nM within a time of 10 min. To conclude, the SNP detection based on this method shows a cheap, fast, visible, and versatile opportunity in sensitive and selective prenatal diagnosis of hereditary diseases with good reproducibility and stability.

SNP detection and population structure evaluation of Salix gordejevii Y. L. Chang et Skv. in Hunshandake Sandland, Inner Mongolia, China.

Single nucleotide polymorphisms (SNPs) are the most abundant and richest form of genomic polymorphism and, hence, are highly favorable markers for genetic map construction and genome-wide association studies. Based on the DNA specific-locus amplified fragment sequencing (SLAF-seq) for large-scale SNP detection, the genetic diversity and population structure of Salix gordejevii Y. L. Chang et Skv., a valuable sand-fixing shrub, was assessed in 199 accessions from 20 populations in Hunshandake Sandland of northern China. A total of 623.15M reads resulted in 30.49 × sequencing depth on average and a mean Q30 of 95.70%, and 2,287,715 SNPs in 178,509 polymorphic SLAF tags were obtained. By discarding minor allele frequency > 0.05 and integrity > 0.8, a total of 93,600 SNPs were retained for population genetic analyses, which revealed that 199 individuals could be divided into six groups based on cross-validation errors. However, this grouping pattern did not match the geographical distribution, indicating that there is no apparent geographic barrier in the blank areas where S. gordejevii was not distributed in Hunshandake Sandland. In addition, the physical distance of linkage disequilibrium decay in the analyzed S. gordejevii individuals was 18.5kb when r 2 = 0.1. The linkage disequilibrium decay distances for different chromosomes varied from 4.6kb (chromosome 16) to 37.8kb (chromosome 3). The obtained SNPs offer suitable marker resources for further genetic and genomic studies and will benefit S. gordejevii breeding programs.

Peptide nucleic acid-assisted colorimetric detection of single-nucleotide polymorphisms based on the intrinsic peroxidase-like activity of hemin-carbon nanotube nanocomposites

Here, taking the advantage of single-stranded (ss) DNA specific nuclease (S1) and peptide nucleic acid (PNA), we demonstrated a novel, rapid, and label-free colorimetric nanosensor for the sensitive and accurate detection of SNPs based on the intrinsic peroxidase-like activity of hemin-functionalized single-walled carbon nanotubes (hemin-SWCNTs). PNA, a man-made mimic of DNA with extraordinary stability toward enzymatic degradation, can effectively protect DNA in the fully matched DNA/PNA duplexes from nuclease digestion. While the DNA in DNA/PNA duplexes containing a mismatch can be cleaved into small fragments. This difference can be visually monitored from the specific color change of TMB/H2O2 system by employing the peroxidase activity of hemin-SWCNTs because of its different aggregation states responding to ssPNA or DNA/PNA duplex. Under optimized conditions, the SNPs in the human tumor suppressor gene TP53 have been successfully genotyped in a linear range of 50–1000 nM with a detection limit of 0.11 nM. Moreover, this platform can effectively discriminate a series of single-base mismatches. This assay avoids the assistance of sophisticated instruments and complicated modifications of probes or nanomaterials, and function well for both cell lysate samples and PCR amplicons from standard cell lines, implying its potential practical applications for bioanalysis and biosensors.

Detection of single nucleotide polymorphisms (SNPs) in HER2, MUC1, ESR1, and BRCA1 genes associated with canine mammary cancer

Worldwide, canine mammary cancer (CMC) is the most frequent type of neoplasia in female dogs, and it is three times more frequent in dogs than in humans. In Colombia, CMC is the second most frequent type of cancer, after skin neoplasia. Genetics is one of the most important factors in- volved in any type of cancer, and the genetic ba- sis of this disease is reflected through line breed- ing due to changes in allelic frequencies that are traceable using molecular markers. This study aimed to detect single nucleotide polymorphisms (SNPs) associated with CMC in blood samples collected from collected from healthy and CMC female dogs at Diego Villegas Toro Veterinary Hospital of Universidad de Caldas (Manizales, Colombia). We designed primers using Primer- BLAST and Primer3, and gene fragments from HER2, MUC1, ESR1, and BRCA1 were amplified to identify SNPs through genome mapping using the UCSC Genome Institute genome browser. We used the genome of Canis lupus familaris Boxer breed [GCF_000002285.3, (CanFam 3.1)] as a refer- ence to compare the gene fragments and SNPs. We associated SNPs with the CMC and control groups by testing odds ratios (OR) through Fish- er’s exact tests to determine an association or risk for CMC. We detected two SNPs for ESR1, three for MUC1, six for HER2, and one for BRCA1. MUC1 was the only gene to display an SNP in an exonic region that resulted in an amino acid substitution (Pro&amp;gt;Thr). No significant differences based on the OR were found, though the majority of SNPs, with the exception of four, were found in females with CMC. We report a novel molecu- lar marker for HER2 that amplifies exons 25–26 and introns 24–25, and highlight the importance of conducting further studies on MUC1 and elu- cidating the role of introns and splicing in candi- date genes associated with CMC.

Heterozygous Single-Nucleotide Polymorphism Genotypes at Heat Shock Protein 70 Gene Potentially Influence Thermo-Tolerance Among Four Zebu Breeds of Nigeria.

Genetic variants at heat shock protein 70 gene and their influence on heat stress (HS) tolerance were studied among selected Nigeria zebu, namely, 25 White Fulani (WF), 21 Sokoto Gudali (SG), 21 Red Bororo (RB), and 23 Ambala (AM). Detection of single nucleotide polymorphism (SNP) followed by determination of genotype and genotypic frequency was made among the selected breeds. The heat tolerance coefficient (HTC) was determined from thermo-related parameters including body temperature, rectal temperature, and respiratory rate. Thermo-Tolerance was evaluated through the SNP–thermo-parameter relationship. Statistical analyses were done using the GLM procedure in SAS. A quantitative real-time/high-resolution melting-based assay detected twelve genetic variants. Five of these were common and shared across all breeds of cattle. Of the remaining seven variants, three were specifically identified in AM, two in SG, and two in RB. Also, SNPs were evaluated and four unique SNPs (C151T, C146T, G90A, and C219A) were identified. Heterozygous animals had lower HTC suggesting their potential to withstand HS than homozygous counterparts. The WF and RB animals had significantly lower values for all parameters (BT, RT, RR, and HTC) compared to AM and SG breeds. Thermo-related parameters were significantly different (P < 0.001), and it is recommended that screening of SNPs in zebu is needed to enable selection for improved thermo-tolerance.

Ultrahigh molecular recognition specificity of competing DNA oligonucleotide strands in thermal equilibrium: a cooperative transition to order

The specificity of molecular recognition is important for molecular self-organization. A prominent example is the biological cell where a myriad of different molecular receptor pairs recognize their binding partners with astonishing accuracy within a highly crowded molecular environment. In thermal equilibrium it is usually admitted that the affinity of recognizer pairs only depends on the nature of the two binding molecules. Accordingly, Boltzmann factors of binding energy differences relate the molecular affinities among different target molecules that compete for the same probe. Here, we consider the molecular recognition of short DNA oligonucleotide single strands. We show that a better matching oligonucleotide can prevail against a disproportionally more concentrated competitor with reduced affinity due to a mismatch. We investigate the situation using fluorescence-based techniques, among them Förster resonance energy transfer and total internal reflection fluorescence excitation. We find that the affinity of certain strands appears considerably reduced only as long as a better matching competitor is present. Compared to the simple Boltzmann picture above we observe increased specificity, up to several orders of magnitude. We interpret our observations based on an energy-barrier of entropic origin that occurs if two competing oligonucleotide strands occupy the same probe simultaneously. Due to their differences in binding microstate distributions, the barrier affects the binding affinities of the competitors differently. Based on a mean field description, we derive a resulting expression for the free energy landscape, a formal analogue to a Landau description of phase transitions reproducing the observations in quantitative agreement as a result of a cooperative transition. The advantage of improved molecular recognition comes at no energetic cost other than the design of the molecular ensemble and the presence of the competitor. As a possible application, binding assays for the detection of single nucleotide polymorphisms in DNA strands could be improved by adding competing strands. It will be interesting to see if mechanisms along similar lines as exposed here contribute to the molecular synergy that occurs in biological systems.