Search For Single Nucleotide Polymorphisms Research Articles

Investigation of genetic markers associated to type 2 diabetes mellitus in Santarém-Pará.

Genetic, epigenetic and environmental factors play an important role in the genesis of Type 2 Diabetes Mellitus (T2D). In the genetic context, one of the strategies used to investigate possible associations with diabetes is the search for Single Nucleotide Polymorphisms (SNPs), involving the comparison of alelle frequencies, the phenotypic variations and other relevant factors, such as environmental influences and lifestyle choices, Thus, the aim of this study was to find the relationship of risk variants for T2D in SNPs (rs4994) in the ADRB3 gene; (rs1799854) in the ABCC8 gene; (rs7901695 and rs12255372) in the TCF7L2 gene; and (rs8050136) in the FTO gene in a sample of the population of the municipality of Santarém (PA), Brazilian Amazon, in the northern region of Brazil. ABCC8 (rs1799854 C>T) showed a statistically significant association with T2D. Each chosen gene and SNP has been previously implicated in T2D risk according to existing scientific literature, owing to their roles in glucose regulation and body fat.

An intelligent blockchain-based access control framework with federated learning for genome-wide association studies

Genome-Wide Association Studies (GWAS) aim to find various variations in human disorders and have become one of the most commonly-used methods to find the pathogenesis and genetic mechanisms of complex diseases. However, the GWAS process needs to frequently search the genome-wide data, especially in the calculation process of multi-party participation. The statistical value calculation and interactive search of Single Nucleotide Polymorphisms (SNPs) and model training processes might easily disclose personal information. Therefore, to solve these problems, we propose a Blockchain-based access control Framework for GWAS with Federated Learning-BFGF. Specifically, before training local models, this framework implements Automated Quality Control (AQC) to guarantee the quality of training data. Design the authentication mechanism in blockchain to filter out users who are malicious attackers to protect the security of other users' information initially. To accelerate the speed of cloud model training and resist multiple attacks in federated learning, propose a periodic aggregation method combining differential privacy mechanisms. Finally, simulated experiments have shown that the BFGF framework can protect the security of genetic data and balance availability and accuracy.

Nanopore Sequencing for De Novo Bacterial Genome Assembly and Search for Single-Nucleotide Polymorphism

Nanopore sequencing (ONT) is a new and rapidly developing method for determining nucleotide sequences in DNA and RNA. It serves the ability to obtain long reads of thousands of nucleotides without assembly and amplification during sequencing compared to next-generation sequencing. Nanopore sequencing can help for determination of genetic changes leading to antibiotics resistance. This study presents the application of ONT technology in the assembly of an E. coli genome characterized by a deletion of the tolC gene and known single-nucleotide variations leading to antibiotic resistance, in the absence of a reference genome. We performed benchmark studies to determine minimum coverage depth to obtain a complete genome, depending on the quality of the ONT data. A comparison of existing programs was carried out. It was shown that the Flye program demonstrates plausible assembly results relative to others (Shasta, Canu, and Necat). The required coverage depth for successful assembly strongly depends on the size of reads. When using high-quality samples with an average read length of 8 Kbp or more, the coverage depth of 30× is sufficient to assemble the complete genome de novo and reliably determine single-nucleotide variations in it. For samples with shorter reads with mean lengths of 2 Kbp, a higher coverage depth of 50× is required. Avoiding of mechanical mixing is obligatory for samples preparation. Nanopore sequencing can be used alone to determine antibiotics-resistant genetic features of bacterial strains.

Genome-wide association study for frozen-thawed sperm motility in stallions across various horse breeds.

The semen quality of stallions including sperm motility is an important target of selection as it has a high level of individual variability. However, effects of the molecular architecture of the genome on the mechanisms of sperm formation and their preservation after thawing have been poorly investigated. Here, we conducted a genome-wide association study (GWAS) for the sperm motility of cryopreserved semen in stallions of various breeds. Semen samples were collected from the stallions of 23 horse breeds. The following semen characteristics were examined: progressive motility (PM), progressive motility after freezing (FPM), and the difference between PM and FPM. The respective DNA samples from these stallions were genotyped using Axiom Equine Genotyping Array. We performed a GWAS search for single nucleotide polymorphism (SNP) markers and potential genes related to motility properties of frozen-thawed semen in the stallions of various breeds. As a result of the GWAS analysis, two SNP markers, rs1141327473 and rs1149048772, were identified that were associated with preservation of the frozen-thawed stallion sperm motility, the relevant putative candidate genes being NME/NM23 family member 8 (NME8), olfactory receptor family 2 subfamily AP member 1 (OR2AP1), and olfactory receptor family 6 subfamily C member 4 (OR6C4). Potential implications of effects of these genes on sperm motility are herein discussed. The GWAS results enabled us to localize novel SNPs and candidate genes for sperm motility in stallions. Implications of the study for horse breeding and genetics are a better understanding of genomic regions and candidate genes underlying stallion sperm quality, and improvement in horse reproduction and breeding techniques. The identified markers and genes for sperm cryotolerance and the respective genomic regions are promising candidates for further studying the biological processes in the formation and function of the stallion reproductive system.

Carrot Consumption Frequency Associated with Reduced BMI and Obesity through the SNP Intermediary rs4445711.

It is unclear whether genetic interactions are involved in the association between vegetable intake and reduced body mass index (BMI) or obesity. We conducted a comprehensive search for single nucleotide polymorphisms (SNPs) which are associated with the interaction between vegetable intake frequency and BMI or obesity. We performed a genome-wide association analysis to evaluate the genetic interactions between self-reported intake of vegetables such as carrot, broccoli, spinach, other green vegetables (green pepper and green beans), pumpkin, and cabbage with BMI and obesity, which is defined as a BMI ≥ 25.0 kg/m2 in the Japanese population (n = 12,225). The mean BMI and prevalence of obesity was 23.9 ± 3.4 kg/m2 and 32.3% in men and 22.1 ± 3.8 kg/m2 and 17.3% in in women, respectively. A significant interaction was observed between rs4445711 and frequency of carrot intake on BMI (p = 4.5 × 10−8). This interaction was slightly attenuated after adjustment for age, sex, alcohol intake, smoking, physical activity and the frequency of total vegetable intake (p = 2.1 × 10−7). A significant interaction was also observed between rs4445711 and frequency of carrot intake on obesity (p = 2.5 × 10−8). No significant interactions that were the same as the interaction between frequency of carrot intake and rs4445711 were observed between the intake frequency of broccoli, spinach, other green vegetables, pumpkin or cabbage and BMI or obesity. The frequency of carrot consumption is implicated in reducing BMI by the intermediary of rs4445711. This novel genetic association may provide new clues to clarify the association between vegetable intake and BMI or obesity.

Candidate genes for productivity identified by genome-wide association study with indicators of class in the Russian meat merino sheep breed.

Genome-wide association studies allow identification of loci and polymorphisms associated with the formation of relevant phenotypes. When conducting a full genome analysis of sheep, particularly promising is the study of individuals with outstanding productivity indicators – exhibition animals, representatives of the super-elite class. The aim of this study was to identify new candidate genes for economically valuable traits based on the search for single nucleotide polymorphisms (SNPs) associated with belonging to different evaluation classes in rams of the Russian meat merino breed. Animal genotyping was performed using Ovine Infinium HD BeadChip 600K DNA, association search was performed using PLINK v. 1.07 software. Highly reliable associations were found between animals belonging to different evaluation classes and the frequency of occurrence of individual SNPs on chromosomes 2, 6, 10, 13, and 20. Most of the substitutions with high association reliability are concentrated on chromosome 10 in the region 10: 30859297–31873769. To search for candidate genes, 15 polymorphisms with the highest association reliability were selected (–log10(р) > 9). Determining the location of the analyzed SNPs relative to the latest annotation Oar_rambouillet_v1.0 allowed to identify 11 candidate genes presumably associated with the formation of a complex of phenotypic traits of animals in the exhibition group: RXFP2, ALOX5AP, MEDAG, OPN5, PRDM5, PTPRT, TRNAS-GGA, EEF1A1, FRY, ZBTB21-like, and B3GLCT-like. The listed genes encode proteins involved in the control of the cell cycle and DNA replication, regulation of cell proliferation and apoptosis, lipid and carbohydrate metabolism, the development of the inflammatory process and the work of circadian rhythms. Thus, the candidate genes under consideration can influence the formation of exterior features and productive qualities of sheep. However, further research is needed to confirm the influence of genes and determine the exact mechanisms for implementing this influence on the phenotype.

Molecular-Genetic Characteristics of Yersinia pestis Strains Isolated in the Mongolian Territory of Transboundary Sailyugem Natural Plague Focus

Objective : investigation of phylogenetic origin and affinity of Yersinia pestis strains isolated from field material collected during the epizootiologic survey of the Mongolian part of trans-boundary Sailyugem natural plague focus. Materials and methods : MLVA25-typing of 81 Y. pestis strains, including 55 isolates from the Mongolian part of transboundary Sailyugem natural plague focus, collected in 2017-2018 was carried out. The plague agent strains isolated in different years in the natural foci of Northwest Mongolia and Southern Siberia were used as comparison group. Whole genome sequencing was performed for 21 Y. pestis strains subspecies pestis isolated in Mongolia in 2018 and 1988-1990 and in Gorny Altai of the Russian Federation in 2012-2016. SNP-typing was conducted on the basis of whole genomes of Y. pestis strains identified in the current research and also genomes from GenBank international database. Search of single nucleotide polymorphisms in Y. pestis genomes was carried out in two ways: by means of snippy v. 4.3.5 software and using mummer v. 3.1 package and a set of the author’s scripts. Phylogenetic reconstruction was conducted with the help of RAxML method. Results and discussion: Results of MLVA25 typing of Y. pestis subsp. pestis demonstrated that the strains isolated in Mongolian and Russian parts of the Sailyugem and Khuukh-Serkh-Munkh-Khairkhan natural foci belong to one common cluster. SNP-typing placed the studied isolates from the Mongolian and Russian territories into 4. ANT phylogenetic line with high level of reliability which testifies to the genetic similarity of the specified pathogen groups. The data of MLVA- and SNP-typing showed insignificant variability of the plague agent in the territory of the Mongolian part of trans-boundary Sailyugem natural plague focus. On the basis of the conducted research and results of epizootiological monitoring of Russia and Mongolia border territories it is possible to draw a conclusion on gradual wide penetration of Y. pestis subsp. pestis mainly into grey marmot settlements in Southeast Altai from Northwest Mongolia.

Detection of Single Nucleotide Polymorphism rs2013162 of IRF6 Gene in Patient with Cleft Lip and Palate

Abstract:
 Background: Cleft lip and palate are congenital disorders which induce affected individuals medically, socially and psychologically. The objective of this study was to investigate the association of Single Nucleotide Polymorphism(SNP); rs2013162 of IRF6 Gene in Patient with Cleft Lip and Palate.
 Materials and Methods: Fifty patients with non-syndromic CL/P were included in present study alongwith fifty individuals with no psychiatric history as controls. In all of the these individuals, search for Single nucleotide polymorphism was carried out by designing sequence specific primers. The sequence was amplified by using Real time PCR and products were investigated by visualizing high resolution melting curve upon HRM-PCR.
 Results: The logistic regression and Hardy-Weinberg equilibrium were applied to investigate the association of IRF6 SNP rs2013162 with disease. Results revealed no association of this polymorphism with non-syndromic CL/P.
 Conclusion: We found no association of IRF6 SNP rs2013162 in patients with non-syndromic CL/P. Further study is required with larger sample size to validate the findings of the present study in Pakistani population and along with this SNP other polymorphisms of the same gene should be analyzed to find out the association with the non-syndromic CL/P.

Performance Improvement of SNP Search Using Multithread Programming

Pattern recognition is an important field in Bioinformatics and a well-known task is the search for Single Nucleotide Polymorphism (SNP). It is possible to search for a known SNP position and analyze it using patterns of DNA bases, called masks. Nonetheless, this process becomes computationally expensive as the amount of available genomic data increases. Thus, in this study, we have developed a parallelization scheme, based on multithread programming, to SNP analysis using masks. In our tests, we noticed that the proposed scheme improved the execution time in 98.05 times when compared with the sequential approach.

Secure top most significant genome variants search: iDASH 2017 competition

BackgroundOne of the 3 tracks of iDASH Privacy & Security Workshop 2017 competition was to execute a whole genome variants search on private genomic data. Particularly, the search application was to find the top most significant SNPs (Single-Nucleotide Polymorphisms) in a database of genome records labeled with control or case. In this paper we discuss the solution submitted by our team to this competition.MethodsPrivacy and confidentiality of genome data had to be ensured using Intel SGX enclaves. The typical use-case of this application is the multi-party computation (each party possessing one or several genome records) of the SNPs which statistically differentiate control and case genome datasets.ResultsOur solution consists of two applications: (i) compress and encrypt genome files and (ii) perform genome processing (top most important SNPs search). We have opted for a horizontal treatment of genome records and heavily used parallel processing. Rust programming language was employed to develop both applications.ConclusionsExecution performance of the processing applications scales well and very good performance metrics are obtained. Contest organizers selected it as the best submission amongst other received competition entries and our team was awarded the first prize on this track.

Machine learning identifies interacting genetic variants contributing to breast cancer risk: A case study in Finnish cases and controls

We propose an effective machine learning approach to identify group of interacting single nucleotide polymorphisms (SNPs), which contribute most to the breast cancer (BC) risk by assuming dependencies among BCAC iCOGS SNPs. We adopt a gradient tree boosting method followed by an adaptive iterative SNP search to capture complex non-linear SNP-SNP interactions and consequently, obtain group of interacting SNPs with high BC risk-predictive potential. We also propose a support vector machine formed by the identified SNPs to classify BC cases and controls. Our approach achieves mean average precision (mAP) of 72.66, 67.24 and 69.25 in discriminating BC cases and controls in KBCP, OBCS and merged KBCP-OBCS sample sets, respectively. These results are better than the mAP of 70.08, 63.61 and 66.41 obtained by using a polygenic risk score model derived from 51 known BC-associated SNPs, respectively, in KBCP, OBCS and merged KBCP-OBCS sample sets. BC subtype analysis further reveals that the 200 identified KBCP SNPs from the proposed method performs favorably in classifying estrogen receptor positive (ER+) and negative (ER−) BC cases both in KBCP and OBCS data. Further, a biological analysis of the identified SNPs reveals genes related to important BC-related mechanisms, estrogen metabolism and apoptosis.

Possible Involvement of the CACNA1E Gene in Migraine: A Search for Single Nucleotide Polymorphism in Different Clinical Phenotypes.

To search for differences in prevalence of a CACNA1E variant between migraine without aura, various phenotypes of migraine with aura, and healthy controls. Familial hemiplegic migraine type 1 (FHM1) is associated with mutations in the CACNA1A gene coding for the alpha 1A (Cav 2.1) pore-forming subunit of P/Q voltage-dependent Ca2+ channels. These mutations are not found in the common forms of migraine with or without aura. The alpha 1E subunit (Cav 2.3) is the counterpart of Cav 2.1 in R-type Ca2+ channels, has different functional properties, and is encoded by the CACNA1E gene. First, we performed a total exon sequencing of the CACNA1E gene in three probands selected because they had no abnormalities in the three FHM genes. In a patient suffering from basilar-type migraine, we identified a single nucleotide polymorphism (SNP) in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760; Minor Allele Frequency 0.2241) hitherto not studied in migraine. In a second step, we determined its occurrence in four groups by direct sequencing on blood genomic DNA: migraine patients without aura (N = 24), with typical aura (N = 55), complex neurological auras (N = 19; hemiplegic aura: N = 15; brain stem aura: N = 4), and healthy controls (N = 102). The Asp859Glu - rs35737760 SNP of the CACNA1E gene was present in 12.7% of control subjects and in 20.4% of the total migraine group. In the migraine group it was significantly over-represented in patients with complex neurological auras (42.1%), OR 4.98 (95% CI: 1.69-14.67, uncorrected P = .005, Bonferroni P = .030, 2-tailed Fisher's exact test). There was no significant difference between migraine with typical aura (10.9%) and controls. We identified a polymorphism in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760) that is more prevalent in hemiplegic and brain stem aura migraine. This missense variant causes a change from aspartate to glutamate at position 859 of the Cav 2.3 protein and might modulate the function of R-type Ca2+ channels. It could thus be relevant for migraine with complex neurological aura, although this remains to be proven.

ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding.

The search for prostate cancer biomarkers has received increased attention and several DNA repair related enzymes have been linked to this dysfunction. Here we report a targeted search for single nucleotide polymorphisms (SNPs) and functional impact characterization of human ALKBH family dioxygenases related to prostate cancer. Our results uncovered a SNP of ALKBH7, rs7540, which is associated with prostate cancer disease in a statistically significantly manner in two separate cohorts, and maintained in African American men. Comparisons of molecular dynamics (MD) simulations on the wild-type and variant protein structures indicate that the resulting alteration in the enzyme induces a significant structural change that reduces ALKBH7’s ability to bind its cosubstrate. Experimental spectroscopy studies with purified proteins validate our MD predictions and corroborate the conclusion that this cancer-associated mutation affects productive cosubstrate binding in ALKBH7.

The rate of weight gain and productivity of a chicken broiler cross with various polymorphic types of the myostatin gene

The search for single nucleotide polymorphisms (SNPs) in the myostatin gene is a promising direction of research as this gene is involved in the development of important biological and productive traits in chickens. Using polymerase chain reaction (PCR-RFLP), allele and genotype frequencies were analyzed in the Cornish chicken breed, line G5, cross Smena-8. Two pairs of primers allowing the PCR product to be obtained in the myostatin gene were used. Two single nucleotide substitutions in exon 1 of the myostatin gene were considered: G/A in position MST2109 and G/С in position MST2244. A significant predominance of deoxynucleotide G over C in MST2244 and deoxynucleotide A over G in MST2109 was observed. No differences in the productive traits between genotypes for MST2109 were detected. The analysis of the allelic variability for locus MST2244 showed statistically significant differences in the weight of live chicken at the age of seven days between the CC and G2G2 genotypes (p < 0.01) and CG2 and G2G2 (p < 0.05). G2G2 individuals (203.52 g) were significantly heavier than the CC (179.5 g) and CG2 (193.95 g) chickens at the age of sevendays. Statistically significant differences between the CC and G2G2 genotypes in live weight at the age of 33 days were revealed (p < 0.05). Thus, this research made it possible to estimate allele frequencies in the myostatin gene in line G5 of the Cornish breed. The results obtained will allow taking into account particular chicken genotypes for the myostatin gene for accelerating the breeding process in the broiler poultry industry.

The rate of weight gain and productivity of chicken broiler cross with various polymorphic types of myostatin gene

The search for single nucleotide polymorphisms (SNP) in the myostatin gene is a promising direction of research as this gene is involved in the development of important biological and productive traits in chicken. Using PCR-RFLP technique, an analysis of allele and genotype frequencies in Cornish chicken breed of G5 line of Smena-8 cross has been conducted. Two pairs of primers allowing PCR product to be obtained in the myostatin gene have been used. Two single nucleotide substitutions on exon 1 of the myostatin gene have been under investigation: G/A in MST2109 and G/С in MST2244. A signifiant predominance of deoxynucleotide G in MST2244 over C and deoxynucleotide A over G in MST2109 has been observed. Differences in productive traits between genotypes in MST2109 were not detected. Analysis of allelic variability by MST2244 locus showed statistically significant differences in live weight at the age of 7 days between CC and G2G2 genotypes (p < 0.01), CG2 and G2G2 (p < 0.05). G2G2 individuals (203.52 g) were significantly heavier than CC (179.5 g) and CG2 (193.95 g) chickens at the age of 7 days. Statistically significant differences between the CC and G2G2 genotypes in live weight at the age of 33 days have been revealed (p < 0.05). Thus, this research has led to a better understanding of allele frequencies in the myostatin gene in line G5 of Cornish breed. The results obtained will allow particular myostatin gene-based genotypes to be taken into account for accelerating the breeding process in the broiler poultry industry.

Genome-wide association study (GWAS) for growth rate and age at sexual maturation in Atlantic salmon (Salmo salar).

Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼480 individuals from the Cermaq Canada broodstock program and search for SNPs associated with growth and age at sexual maturation. Using a mixed model approach we identified markers showing a significant association with growth, grilsing (early sexual maturation) and late sexual maturation. The most significant associations were found for grilsing, with markers located in Ssa10, Ssa02, Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28, Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13. Candidate genes, which were linked to these genetic markers, were identified and some of them show a direct relationship with developmental processes, especially for those in association with sexual maturation. However, the relatively low power to detect genetic markers associated with growth (days to 5 kg) in this GWAS indicates the need to use a higher density SNP array in order to overcome the low levels of linkage disequilibrium observed in Atlantic salmon before the information can be incorporated into a selective breeding program.

SLC25A24 as a novel susceptibility gene for low fat mass in humans and mice.

Genetic factors contribute to the development of obesity. The aim of this study was to identify novel genes that regulate body fat mass. We performed a search for single nucleotide polymorphisms (SNPs) associated with body fat percentage using SNP arrays and undertook a replication study and animal study. Baseline examinations were conducted in 251 (first-stage analysis), 499 (second-stage analysis), and 732 (additional analyses) Japanese postmenopausal women. The mean age (mean ± SD) of the subjects was 66.5 ± 9.4 years. We also analyzed the fat-related phenotypes of a candidate gene in knockout mice. In the analysis of total body fat, we focused on an SNP of SLC25A24 that showed the lowest significant P value obtained from multiple comparison tests among Japanese postmenopausal women. A significant association was also found between SLC25A24 SNPs and body mass index in the 1482 Japanese postmenopausal women examined in the study. The SLC25A24 SNPs affected the mRNA expression of SLC25A24 in human preadipocytes. Compared with wild-type mice, Slc25a24-KO mice had significantly lower body weights and white adipose tissue weights. Adipocyte differentiation was inhibited in Slc25a24-KO adipose tissues and Slc25a24-knockdown adipocytes. Genetic analyses in human and mouse models revealed the importance of SLC25A24/Slc25a24 in the regulation of body fat mass and adipogenesis.

Large-scale detection and application of expressed sequence tag single nucleotide polymorphisms in Nicotiana.

Single nucleotide polymorphisms (SNPs) are widespread in the Nicotiana genome. Using an alignment and variation detection method, we developed 20,607,973 SNPs, based on the expressed sequence tag sequences of 10 Nicotiana species. The replacement rate was much higher than the transversion rate in the SNPs, and SNPs widely exist in the Nicotiana. In vitro verification indicated that all of the SNPs were high quality and accurate. Evolutionary relationships between 15 varieties were investigated by polymerase chain reaction with a special primer; the specific 302 locus of these sequence results clearly indicated the origin of Zhongyan 100. A database of Nicotiana SNPs (NSNP) was developed to store and search for SNPs in Nicotiana. NSNP is a tool for researchers to develop SNP markers of sequence data.

Identification of SNPs linked to eight apple disease resistance loci

Although genetic and genomic studies have progressed to a very advanced level in apple, the application of this acquired knowledge for marker-assisted breeding (MAB) remains limited mainly to pyramiding monogenetically inherited resistances against apple scab, powdery mildew and fire blight. Crucial contributing reasons are the uncertainty in map position of some genes and the lack of tightly linked markers suitable for high-throughput analysis (HTA) that reduces the costs of MAB. Single-nucleotide polymorphism (SNP) markers have the potential to resolve these major issues. Here we present the refined map positions of the apple scab resistance genes Rvi2, Rvi4 and Rvi11, and the systematic search for SNPs associated with apple scab (Rvi2, Rvi4, Rvi6, Rvi11, Rvi15), powdery mildew (Pl2) and fire blight (FB_E and FB_MR5) resistances. With the aid of the ‘Golden Delicious’ sequence, several SNPs linked to each of the eight resistances were identified in the genomic regions around the resistance loci previously delimited by simple sequence repeat markers. The specificity of the alleles in coupling with the resistances was determined by screening eight apple genotypes, six of them being founding clones of modern apple cultivars. These SNPs can now be used to develop SNP-based HTA assays for MAB.

Corrigendum to “Hypothesis driven single nucleotide polymorphism search (HyDn-SNP-S)” [DNA Repair 12 (September (9)) (2013) 733–740

For the melanoma, breast and lung cancer studies, the same atabases were used to identify the SNPs in the genes of interst and perform the statistical analysis. In the case of the prostate ancer study, the SNP database that was used to mine the NPs was phs000306.v2.p1, by using the publicly available SNP ata. That is, a different SNP data set (phs000306.v2.p1) was used o obtain the SNPs than the database used for the subsequent tatistical analysis (phs000207.v1.p1). This does not change any f our results, in fact it reinforces our method. This is because he list of SNPs associated with prostate cancer was obtained rom a different study than the one that was analysed for ignificance. However, the fact that 11 of the SNPs obtained rom phs000306.v2.p1 was determined to be statistically signifcantly associated with prostate cancer (see main text) when nalysing the phs000207.v1.p1 database provides validation for our ethod. The acknowledgement section should include the following tatement: