Table_2_Single Nucleotide Polymorphism Analysis Indicates Genetic Distinction and Reduced Diversity of Swine-Associated Methicillin Resistant Staphylococcus aureus (MRSA) ST5 Isolates Compared to Clinical MRSA ST5 Isolates.xlsx
The use of genome-wide single nucleotide polymorphism (SNP) data has recently proven useful in the study of human population structure. We have studied the internal genetic structure of the Swedish population using more than 350,000 SNPs from 1525 Swedes from all over the country genotyped on the Illumina HumanHap550 array. We have also compared them to 3212 worldwide reference samples, including Finns, northern Germans, British and Russians, based on the more than 29,000 SNPs that overlap between the Illumina and Affymetrix 250K Sty arrays. The Swedes - especially southern Swedes - were genetically close to the Germans and British, while their genetic distance to Finns was substantially longer. The overall structure within Sweden appeared clinal, and the substructure in the southern and middle parts was subtle. In contrast, the northern part of Sweden, Norrland, exhibited pronounced genetic differences both within the area and relative to the rest of the country. These distinctive genetic features of
Henry, RJ, Bundock, PC, Pacey-Miller, T, Kennedy, BG, Ablett, GA, Waters, DLE & Jin,QS 2003, Single nucleotide polymorphism analysis in support of plant breeding, paper presented to the 12th Australasian Plant Breeding Conference, Perth, WA, 15-20 September.. ...
The identification of copy number aberration in the human genome is an important area in cancer research. We develop a model for determining genomic copy numbers using high-density single nucleotide polymorphism genotyping microarrays. The method is based on a Bayesian spatial normal mixture model with an unknown number of components corresponding to true copy numbers. A reversible jump Markov chain Monte Carlo algorithm is used to implement the model and perform posterior inference. The performance of the algorithm is examined on both simulated and real cancer data, and it is compared with the popular CNAG algorithm for copy number detection. We demonstrate that our Bayesian mixture model performs at least as well as the hidden Markov model based CNAG algorithm and in certain cases does better. One of the added advantages of our method is the flexibility of modeling normal cell contamination in tumor samples.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 ...
Read "Associations between three common single nucleotide polymorphisms (rs266729, rs2241766, and rs1501299) of ADIPOQ and cardiovascular disease: a meta-analysis, Lipids in Health and Disease" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Recent technological progress has permitted the efficient performance of genome-wide association studies (GWAS) to map genetic variants associated with common diseases. Here, we analyzed 2,893 single nucleotide polymorphisms (SNPs) that have been identified in 593 published GWAS as associated with a disease phenotype with respect to their genomic location. In absolute numbers, most significant SNPs are located in intergenic regions and introns. When compared to their representation on the chips, there is essentially overrepresentation of nonsynonymous coding SNPs (nsSNPs), synonymous coding SNPs, and SNPs in untranscribed regions upstream of genes among the disease associated SNPs. A Gene Ontology term analysis showed that genes putatively causing a phenotype often code for membrane associated proteins or signal transduction genes.. ...
Pharmacological potency, side effect, and kinetics in body are influenced by single nucleotide polymorphisms of genes encoding key proteins controlling drugs
In regions where malaria is endemic, individuals are often infected with multiple distinct parasite genotypes, a situation that may impact on evolution of parasite virulence and drug resistance. Most approaches to studying genotypic diversity have involved analysis of a modest number of polymorphic loci, although whole genome sequencing enables a broader characterisation of samples. PCR-based microsatellite typing of a panel of ten loci was performed on Plasmodium falciparum in 95 clinical isolates from a highly endemic area in the Republic of Guinea, to characterize within-isolate genetic diversity. Separately, single nucleotide polymorphism (SNP) data from genome-wide short-read sequences of the same samples were used to derive within-isolate fixation indices (F ws), an inverse measure of diversity within each isolate compared to overall local genetic diversity. The latter indices were compared with the microsatellite results, and also with indices derived by randomly sampling modest numbers ...
Coronary Heart Disease (CHD) is one of the leading causes of death in the world with a projected global 82 million DALYs by 2020. Genetic and environmental factors contribute to CHD development. Here, the authors investigate the association between CHD risk and three Single Nucleotide Polymorphisms (SNPs) in the AdipoQ gene (rs3774261, rs1063537 and rs2082940); and the interaction of this association with environmental factors, in Northeast Han Chinese population. Using a case-control study design, 1514 participants (754 cases and 760 controls) were investigated. Three variants in the AdipoQ gene (rs3774261, rs1063537 and rs2082940) were selected and genotyped. The online SNPstats program and SPSS 21.0 software were used for data analyses. The authors found that the rs3774261G allele is associated with the risk of CHD but that the rs2082940T allele protects against CHD. No significant association was found between rs1063537 and CHD risk. The study also found significant interactions between triglyceride
We questioned the significance of haplotype structure in gene regulation by testing whether individual single nucleotide polymorphisms (SNPs) within a gene promoter region [interleukin-1-beta (IL1B)] might affect promoter function and, if so, whether function was dependent on haplotype context. We sequenced genomic DNA from 25 individuals of diverse ethnicity, focusing on exons and upstream flanking regions of genes of the cluster. We identified four IL1B promoter region SNPs that were active in transient transfection reporter gene assays. To substantiate allelic differences found in reporter gene assays, we also examined nuclear protein binding to promoter sequence oligonucleotides containing different alleles of the SNPs. The effect of individual SNPs on reporter gene transcription varied according to which alleles of the three other SNPs were present in the promoter construct. The SNP patterns that influenced function reflected common haplotypes that occur in the population, suggesting ...
Genome‐wide association studies have successfullyidentified many novel genetic loci for various human complex diseases and quantitative traits
TABLE-US-00003 TABLE 3 SNPs associated with adolescent idiopathic scoliosis Case Control Allele1/2 Genotype count Genotype count Odds ratiob dbSNP ID Risk Study 11 12 22 RAF 11 12 22 RAF P valuea (95% CI) Pheic rs11190870 T/C GWAS 449 470 114 0.662 479 728 266 0.572 1.27.E-10 1.46 (1.30-1.65) T Replication 152 148 26 0.693 3129 4809 1883 0.563 5.13.E-11 1.75 (1.48-2.07) Combinedd 601 618 140 0.670 3608 5537 2149 0.565 1.24.E-19 1.56 (1.41-1.71) 0.0881 rs625039 G/A GWAS 533 424 76 0.721 600 695 178 0.643 4.75.E-09 1.43 (1.27-1.62) G Replication 172 135 19 0.735 1297 4579 3947 0.635 1.69.E-07 1.59 (1.34-1.90) Combinedd 705 559 95 0.724 1475 5274 4547 0.636 4.30.E-15 1.49 (1.35-1.65) 0.341 rs11598564 A/G GWAS 297 508 228 0.533 310 724 439 0.456 9.40.E-08 1.36 (1.22-1.53) G Replication 107 156 63 0.567 2107 4837 2879 0.461 8.82.E-08 1.54 (1.31-1.80) Combinedd 404 664 291 0.542 2417 5531 3318 0.46 5.98.E-14 1.42 (1.30-1.56) 0.226 Allele 1 represents major allele. Allele 1/2 is shown according to (+) ...
Novel Single Nucleotide Polymorphisms and Combinations of Novel and Known Polymorphisms for Determining the Allele-Specific Expression of the IGF2 Gene - diagram, schematic, and image 42 ...
Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: ...
BACKGROUND Non-synonymous single nucleotide polymorphisms (SNPs) within vital DNA repair genes may cause reduction of activity leaving the genome unrepaired resulting in genomic instability and cancer. MATERIALS AND METHODS The present endeavour involved study on the association of the SNP rs13181 (Lys751Gln/A18911C) in the Nucleotide Excision Repair (NER) pathway gene ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) with the risks of Squamous Cell Carcinomas of the Head and Neck (SCCHN) and Breast cancer using a case-control based association study among 685 (400 controls and 285 SCCHN-affected cases) and 395 (227 normal healthy female controls and 168 breast cancer cases) ethnically-matched samples, respectively from north India using Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. RESULTS Results showed significant association of rs13181 homozygous mutant (CC) [Odds Ratio (OR) 4.412, 95% Confidence
Objective: The objective of this study is to determine the associations among genetic variations in the P2X7 receptor gene, decreased bone mineral density (BMD), and the risk of osteoporosis in patients aged older than 50 years with ankle fractures. Methods: Patients were genotyped for 15 nonsynonymous single-nucleotide polymorphisms (SNPs) in the P2X7 gene. The sample was divided into two groups according to the bone densitometry results: an intervention group with osteopenia (T scores between -1.0 and -2.5) or osteoporosis (T scores ≤ -2.5) and a control group with values within the normal range (T scores ≥ -1). A total of 121 patients were evaluated: 65 in the intervention group and 56 in the control group. Results: The results suggested that SNPs 1, 4, 11, 13, 14, and 15 were loss-of-function (LOF) variants. SNP 12 was also associated with LOF in our population, but its RNA expression has not been analyzed to date. Conclusions: In conclusion, we demonstrate that functional polymorphisms ...
Detecting causal single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) has been focusing on measuring the statistical power of single SNPs, which have a relatively small effect on predicting disease susceptibility and ignore prior biological information about the target disease. Especially in complex diseases such as type 2 diabetes (T2D), the effect of each single SNP is too small to explain the disease association significantly.. To enhance the statistical power, we propose considering combinations of SNPs. Yang et al. discovered that estimates of variance explained by genome-wide SNPs are unbiased with the proportion of SNPs used to estimate genetic relationships in human height [1]. Although SNPs with relatively low statistical power are considered together, the statistical power is not significantly affected. In addition, Park et al. compared the discriminatory power of the risk models in Crohns disease and prostate and colorectal (BPC) cancer and found that a ...
TY - JOUR. T1 - An investigation of modifying effects of single nucleotide polymorphisms in metabolism-related genes on the relationship between peripheral nerve function and mercury levels in urine and hair. AU - ​Wang, ​Yi AU - Goodrich, Jaclyn M.. AU - Werner, Robert. AU - Gillespie, Brenda. AU - Basu, Niladri. AU - Franzblau, Alfred. PY - 2012/2/15. Y1 - 2012/2/15. N2 - Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n = 515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects ...
A number of previous studies suggested the presence of deleterious amino acid altering nonsynonymous single-nucleotide polymorphisms (nSNPs) in human populations. However, the proportions of deleterious nSNPs among rare and common variants are not known. To estimate these, ,77?000 SNPs from human protein-coding genes were analyzed. Based on two independent methods, this study reveals that up to 53% of rare nSNPs (minor allele frequency (MAF),0.002) could be deleterious in nature. The fraction of deleterious nSNPs declines with the increase in their allele frequencies and only 12% of the common nSNPs (MAF,0.4) were found to be harmful. This shows that even at high frequencies significant fractions of deleterious polymorphisms are present in human populations. These results could be useful for genome-wide association studies in understanding the relative contributions of rare and common variants in causing human genetic diseases ...
The vast majority of drugs act through binding to their protein targets. Prediction of the interaction between small molecules and these receptors is a key elem...
Researchers believe there are some 10 million common SNPs in the human genome. Scanning the genomes of large numbers of patients for such a large number of variants would be prohibitively expensive. Fortunately, a major shortcut has been discovered that reduces the workload about 30-fold. When the International HapMap Project was completed in October 2005, the researchers demonstrated that the 10 million variants cluster into local neighborhoods, called haplotypes, and that they can be accurately sampled by as few as 300,000 carefully chosen SNPs. New technological systems allow these SNPs to be systematically studied in high-throughput facilities that dramatically lower the cost.. In genome-wide association studies, researchers compare the genomes of people with an illness, who are referred to as cases, to unaffected people, who are referred to as controls. Through this comparison, it becomes possible to identify the genetic differences between sick and healthy people, even when the genetic ...
TY - JOUR. T1 - Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer. AU - Burri, Ryan J.. AU - Stock, Richard G.. AU - Cesaretti, Jamie A.. AU - Atencio, David P.. AU - Peters, Sheila. AU - Peters, Christopher A.. AU - Fan, Grace. AU - Stone, Nelson N.. AU - Ostrer, Harry. AU - Rosenstein, Barry S.. PY - 2008/7. Y1 - 2008/7. N2 - The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam ...
To the Editors:. Asthma is a complex disease characterised by inflammation and remodelling of the airways. Over the past few decades enormous progress has been made to understand which genes are associated with asthma development and several interactions between genes and environmental factors have been elucidated. Investigations into genetic and gene expression profiling, as well as single nucleotide polymorphism analyses, have helped to better understand the underlying molecular mechanisms of asthma. However, the recent identification of novel regulatory functions for transposable and transposed genetic elements (TEs) may be an important and new key to help understand the genetics that cause the heterogeneous manifestations of the asthma pathology.. Approximately 45% of the human genome is made of TEs [1]. The vast majority of TEs originate from retrotransposition of genetic elements known as short and long interspersed nuclear elements, long terminal repeat-superfamilies and direct ...
... One of the most significant outcomes of the Human Genome Project has been the iden- tification of large numbers of single nucleotide polymorphisms (SNPs) [1-3]. The ap-plication ...
Çfarë janë SNP-te - single nucleotide polymorphisms? Polimorfizmi i një nukleotidi te vetëm, te quajtur shpesh SNP (single nucleotide polymorphisms) janë lloji i variacionit me i shpeshte midis njerezve. Çdo SNP përfaqëson një diference ne një njësi te vetme te ADN-së, te quajtur nukleotid. Për shembull, një SNP mund te zevendesoje nukleotidin citozinë (C) me…
Beth Robb awarded the Stephen J. OBrien Award for the best student paper published in the Journal of Heredity for the paper Robb, E.A., C.L. Gitter, H. Cheng and M.E. Delany. 2011. Single nucleotide polymorphism analysis of chicken genetic resources: Variation within and among MHC-congenic lines and mapping of developmental mutations. J. Heredity 102:141-156. (cover art ...
Single nucleotide polymorphisms, frequently called SNPs are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block called a nucleotide. SNPs occur normally throughout a persons DNA. They occur in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in a disease by affecting the genes function. It has been proposed that SNPs may help predict an individuals response to certain drugs, susceptibility to environmental factors such as toxins and risk of developing particular diseases such as cancer.. SNPs, which are single base-pair variations in the DNA sequence of the genome, have been found to be associated with breast cancer ...
OLIVEIRA, Martha Maria de et al. Single Nucleotide Polymorphisms (SNPs) of the TNF-a (-238/-308) gene among TB and nom TB patients: susceptibility markers of TB occurrence?. J. bras. pneumol. [online]. 2004, vol.30, n.4, pp.371-377. ISSN 1806-3713. https://doi.org/10.1590/S1806-37132004000400012.. BACKGROUND: Host genetic factors may play a role in the susceptibility to active tuberculosis (TB), and several polymorphisms in different cytokine coding genes have been described and associated with diseases to date. OBJECTIVES: To investigate whether polymorphisms within the promoter region of the TNF-a (-238/-308) coding genes are associated to the occurrence of active TB. METHODS: SNPs within the TNF-a gene were analyzed by PCR-RFLP among two groups of individuals: patients with TB (n = 234, and patients non TB (n = 113). RESULTS: In this study, the presence of the -238A allele was associated with susceptibility to TB disease occurrence and severity (p = 0,00002; OR = 0,15; IC = 0,06-0,36. On the ...
A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10(-18)] and B*81:01 (OR = 4.8; P= 1.3 × 10(-9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10(-21)) and explains ...
Purpose: MicroRNAs regulate gene expression by binding to the 3′‐untranslated region (UTR) of target genes. Single‐nucleotide polymorphisms of critical genes may affect their regulation by microRNAs. We have identified a single nucleotide polymorphism within the miR‐502 seed binding region in the 3′‐UTR of the SET8 gene. SET8 methylates TP53 and regulates genome stability. We investigated the role of this SET8 single nucleotide polymorphism and in concert with the TP53 codon72 single nucleotide polymorphism in the propensity for onset of breast cancer.. Experimental Design: We measured the SET8 single nucleotide polymorphisms in a case‐control study on 1110 breast cancer cases and 1097 controls.. Results: The SET8 CC and TP53 GG genotypes were independently associated with an earlier age of breast cancer onset in an allele‐dose‐dependent manner (for SET8, 52.2 years for TT, 51.4 for TC, and 49.5 for CC; and for TP53, 53.1 years for CC, 51.5 for GC, 50.7 for GG). Individuals ...
This study analyzed SNPs in the IL33 gene in Chinese patients with ischemic stroke for the first time. We investigated four SNPs in IL33 gene (rs4742170, rs1929992, rs10975519, rs16924159), and discovered two SNPs (rs4742170, rs1929992) were significantly associated with ischemic stroke at univariate analysis. Moreover, the rs4742170 polymorphism remained significant association with ischemic stroke in three models after adjustment for Binary Logistic Regression.. Many studies have reported that IL-33 could support Th2 cells, reduce macrophage foam cell formation and, probably, modulate endothelial cell function [20, 21], which may play important roles in the series of events involve in the pathogenesis and development of stroke. Recently, it has been reported that IL-33/ST2 pathway can protect against atherosclerosis and adipose tissue inflammation which are well-known risk factors for ischemic stroke [21].. In this study, we reported the significant association of the rs4742170 SNP in IL33 ...
Background and Purpose: Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS.. Methods: Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model.. Results: Despite having power to detect odds ratio of ...
Background Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy.. Method In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods.. Results In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI ...
Single nucleotide polymorphisms (SNPs) are single nucleotide variations which comprise the most wide spread source of genetic diversity in the genome. Currently, SNPs serve as markers for genetic predispositions, clinically evident disorders and diverse drug responses. Present SNP diagnostics are primarily based on enzymatic reactions in different formats including sequencing, polymerase-chain reaction (PCR) and microarrays. In these assays, the enzymes are applied to address the required sensitivity and specificity when detecting SNP. On the other hand, the development of enzyme-free, simple and robust SNP sensing methods is in a constant focus in research and industry as such assays allow rapid and reproducible SNP diagnostics without the need for expensive equipment and reagents. An ideal method for detection of SNP would entail mixing a DNA or RNA target with a probe to directly obtain a signal. Current assays are still not fulfilling these requirements, although remarkable progress has been
Heres the definition of an SNP …. "Single nucleotide polymorphisms, frequently called SNPs (pronounced "snips"), are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.. SNPs occur normally throughout a persons DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the genes function.. Most SNPs have no effect on health or development. Some of these genetic differences, however, have proven to be very important in the study ...
The increasing interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) emphasis the need for high-throughput and cost effective scoring methods. Pyrosequencing is a novel method for screening SNPs. In this study we examine breed specific SNPs in the pig melanocortin I receptor gene (MC1R), some causing coat color phenotypes. A total of fifteen pigs representing eight breeds and crosses were analyzed by pyrosequencing. In addition to nine previously known SNPs, we also detected one new missense mutation by pyrosequencing. We here show that the SNPs were readily scored using standard reaction conditions. Insertions as well as substitutions were unambiguously detected and all genotypes were resolved in terms of homo- and heterozygozity.. ...
A Single Nucleotide Polymorphism or SNP (pronounced snip) is a DNA sequence variation, occurring when a single nucleotide: adenine (A), thymine (T), cytosine (C) or guanine (G) - in the genome is altered. A variation must occur in at least 1% of the population to be considered a SNP. SNPs make up 90% of all human genetic variations, and occur every 100 to 300 bases along the human genome. Two of every three SNPs substitute Cytosine (C) with Thymine (T). Variations in the DNA sequences of humans can affect how humans handle diseases, bacteria, viruses, chemicals, drugs, etc. SNPs are of great value to biomedical research and in developing pharmacy products. Because SNPs do not change much from generation to generation, following them during population studies is straightforward. SNPs are generally considered to be a form of point mutation that has been evolutionarily successful enough to recur in a significant proportion of a species population. ...
In the era of genome-wide association studies (GWAS) and personalized medicine, predicting the impact of single nucleotide polymorphisms (SNPs) in regulatory elements is an important goal. Current approaches to determine the potential of regulatory SNPs depend on inadequate knowledge of cell-specific DNA binding motifs. Here, we present Sasquatch, a new computational approach that uses DNase footprint data to estimate and visualize the effects of noncoding variants on transcription factor binding. Sasquatch performs a comprehensive k-mer-based analysis of DNase footprints to determine any k-mers potential for protein binding in a specific cell type and how this may be changed by sequence variants. Therefore, Sasquatch uses an unbiased approach, independent of known transcription factor binding sites and motifs. Sasquatch only requires a single DNase-seq data set per cell type, from any genotype, and produces consistent predictions from data generated by different experimental procedures and at
BackgroundThe Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G|A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer. MethodologyWe conducted a search of case-control studies on the associations of Bax-248G|A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis
DUGi: Viewing Item from repository Recercat: Delta-like 1 homolog (DLK1) gene encodes a transmembrane protein containing epidermal growth factor-like repeats that promotes the induction of mesenchymal cells but prevents chondrocyte, preadipocytes and osteoblast maturation and differentiation. Rs1802710 polymorphism situated in the fifth exon of DLK1, shows a significant parent-of-origin effect reflecting the known silencing of the maternally inherited copy by imprinting. In humans, a more frequent paternal transmission of the paternal allele in the rs1802710 polymorphism of DLK1 on obese children has been noticed. We aimed to study the single nucleotide polymorphism (SNP) rs1802710 of the DLK1 gene and its effects on early life development. Due to the known imprinting effect surrounding the DLK1 locus, we wanted to analyze whether these changes were different depending on the parental origin of the transmitted rs1802710 variant T allele. Therefore, a longitudinal study has been done from the beginning
Emphasis in this course is on strategies for genetic mapping of complex human traits. It will include theory as well as practical exercises. The exercises will be carried out using a variety of computer programs (PLINK, GenABEL, MACH, UNPHASED, EIGENSTRAT, Variant Association Tools (VAT), SEQPower and R, etc.). Topics covered include: Association analysis of qualitative and quantitative traits; single marker and haplotype analysis; analysis of whole genome association study data; complex trait rare variant association analysis of next generation sequence data; data quality control for genotype and next generation sequence data; haplotype reconstruction; controlling population admixture (genomic control, principal components analysis, etc); imputing genotype data from sequence and genotype data; detecting gene x gene and gene x environmental interactions; power and sample size estimation for both genotype and rare variant data; permutation (estimating empirical p-values); and false discovery rate ...
We appreciate the interest of Dr Frau et al1 in our genome-wide association analysis of blood pressure response to the angiotensin II receptor antagonist, candesartan, in which single nucleotide polymorphism associations were validated by demonstrating opposite direction associations with blood pressure response to the thiazide diuretic, hydrochlorothiazide.2 In lieu of multiple, independent same-race candesartan-treated samples available for replication analyses, this approach to single nucleotide polymorphism validation was motivated by the observation that all known predictors of blood pressure response to inhibitors of the renin-angiotensin system (eg, plasma renin activity, race, and age) have opposite direction associations with blood pressure response to diuretics.3 Although some methodological differences could conceivably account for nonreplication of the opposite direction associations for 6 lead single nucleotide polymorphisms tested by Dr Frau et al, our statistical analysis was ...
In most existing genetic variant association studies, "common trait, common variants", which asserts that common genetic variants contribute to most of traits (disease susceptibilities), serves as the central assumption. Researchers have successfully identified some significant associations between common single nucleotide polymorphisms (SNPs) and disease traits [1]. However, despite the enormous efforts expended on association studies of complex traits, common genetic variants only show a moderate influence on different phenotypes in many reported disease associations and consequently have limited diagnostic value [2, 3]. While the identification of common variants creates a dilemma, known as "common trait, rare variants", an alternative hypothesis, which asserts that multiple rare variants with moderate to high penetrances may collectively influence disease susceptibilities, has been suggested in some literatures [3-5]. Rare variants are defined as those whose minor allele frequencies (MAF) ...
We have conducted a pathway-based analysis of genome-wide single-nucleotide polymorphism (SNP) data in order to identify genetic susceptibility factors for cervical cancer in situ. Genotypes derived from Affymetrix 500k or 5.0 arrays for 1076 cases and 1426 controls were analyzed for association, and pathways with enriched signals were identified using the SNP ratio test. The most strongly associated KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were Asthma (empirical P=0.03), Folate biosynthesis (empirical P=0.04) and Graft-versus-host disease (empirical P=0.05). Among the 11 top-ranking pathways were 6 related to the immune response with the common denominator being genes in the major histocompatibility complex (MHC) region on chromosome 6. Further investigation of the MHC revealed a clear effect of HLA-DPB1 polymorphism on disease susceptibility. At a functional level, DPB1 alleles associated with risk and protection differ in key amino-acid residues affecting peptide-binding motifs ...
Purpose : Glaucoma is a serious eye disease that often leads to blindness. Glaucoma is often described as a degenerative optic neuropathy that is associated with elevated intraocular pressure. Primary glaucoma is a hereditary disease that affects both human and canines. But the genetic mutations association with glaucoma is not fully investigated. Methods : Previously, we have shown a specific association of two single nucleotide polymorphisms (SNPs) with glaucoma in Shiba-Inus and Shih-Tzus. In this study, we screened polymorphisms within SRBD1 and CYP1B1 genes that have been shown to be associated with Glaucoma in several dog breeds. 77 healthy dogs and 135 cases dogs were recruited from the Centre Hospitalier Veterinaire Saint-Martin (France), and from the REOVVA member (European Network in Veterinary Ophthalmology and Vision in Animals). All Dogs were clinically evaluated before taking blood samples for direct sequencing Analysis. Results : Two new SNPs (rs9172407 and rs22115601) within ...
Polymorphic markers at bovine gene loci facilitate the integration of cattle genetic maps with those of humans and mice. To this end, 31 single nucleotide polymorphism (SNP) markers were developed for seven bovine chemokine genes. Loci were amplified from bovine genomic DNA by the polymerase chain reaction, and candidate amplicons were sequenced to determine their identity. Amplified loci from 24 founding parents and select progeny from a beef cattle reference population were sequenced and analyzed for SNPs. SNP haplotype alleles were determined by examining segregation patterns and used to establish the locus position on the bovine linkage map. Loci for growth-related proteins (GRO3, GRO1, and GROX) were clustered with the related CXC chemokine genes, interleukin (IL) 8, and epithelial cell inflammatory protein 1, at 84 cM from the centromeric end of the bovine chromosome (BTA) 6 linkage group. Bovine loci for a cluster of IL8 receptors, a stromal cell-derived factor 1, interferong, and tumor necrosis
A team led by the University of California San Diego has developed a chip that can detect a type of genetic mutation known as a single nucleotide polymorphism (SNP) and send the results in real time to a smartphone, computer, or other electronic device. The chip is at least 1,000 times more sensitive at detecting an SNP than current technology.. The advance, published July 9 in Advanced Materials, could lead to cheaper, faster and portable biosensors for early detection of genetic markers for diseases such as cancer.. An SNP is the change in a single nucleotide base (A, C, G or T) in the DNA sequence. It is the most common type of genetic mutation. While most SNPs have no discernible effect on health, some are associated with increased risk of developing pathological conditions such as cancer, diabetes, heart disease, neurodegenerative disorders, autoimmune and inflammatory diseases.. Traditional SNP detection methods have several limitations: they have relatively poor sensitivity and ...
from June 26-30, 2017. The goal of the course is to teach course participants both theory and application of methods for population based association analysis, with a concentration on the analysis of exome and whole genome sequence and genotype data.Emphasis in this course is on strategies for genetic mapping of complex human traits. It will include theory as well as practical exercises. The exercises will be carried out using a variety of computer programs (PLINK, GenABEL, MACH, UNPHASED, EIGENSTRAT, Variant Association Tools (VAT), SEQPower and R, etc.). Topics covered include: Association analysis of qualitative and quantitative traits; single marker and haplotype analysis; analysis of whole genome association study data; complex trait rare variant association analysis of next generation sequence data; data quality control for genotype and next generation sequence data; haplotype reconstruction; controlling population admixture (genomic control, principal components analysis, etc); imputing ...
Background: Single Nucleotide Polymorphisms (SNPs) are widely used molecular markers, and their use has increased massively since the inception of Next Generation Sequencing (NGS) technologies, which allow detection of large numbers of SNPs at low cost. However, both NGS data and their analysis are error-prone, which can lead to the generation of false positive (FP) SNPs. We explored the relationship between FP SNPs and seven factors involved in mapping-based variant calling - quality of the reference sequence, read length, choice of mapper and variant caller, mapping stringency and filtering of SNPs by read mapping quality and read depth. This resulted in 576 possible factor level combinations. We used error- and variant-free simulated reads to ensure that every SNP found was indeed a false positive. Results: The variation in the number of FP SNPs generated ranged from 0 to 36,621 for the 120 million base pairs (Mbp) genome. All of the experimental factors tested had statistically significant ...
BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case-control approach. FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status ...
The global single nucleotide polymorphism (SNP) genotyping market is expected to grow to more than $11.5 billion by 2019, with a five-year compound annual growth rate (CAGR) of 21.9%. The Asia-Pacific region is anticipated to move at a significant 24.1% CAGR.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population.. Methods A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ2 test using Stata.. Results Association to the CD40 gene was robustly replicated (p=2×10−4, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the ...
Objective. Low birth weight is associated with an increased risk of type 2 diabetes. The mechanisms underlying this association are unknown and may represent intrauterine programming or two phenotypes of one genotype. The fetal insulin hypothesis proposes that common genetic variants that reduce insulin secretion or action may predispose to type 2 diabetes and also reduce birth weight, since insulin is a key fetal growth factor. We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight.. Research design and methods. We genotyped single nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2 and SLC30A8) in 7986 mothers and 19200 offspring from four studies of white Europeans. We tested the association between maternal or fetal genotype at each locus and birth weight of the offspring.. Results. We found that type 2 diabetes risk alleles at the CDKAL1 and HHEX-IDE loci were associated with ...
Understanding the genetic architecture of complex polygenic traits is a fundamental goal of modern biological and medical research, and the currently favored experimental paradigm is association mapping (reviewed by Carlson et al. [1]). Association studies genotype a dense set of single nucleotide polymorphisms (SNPs) in a large panel of individuals and test each SNP, or set of local haplotypes constructed from the SNP data, for a phenotype/disease association. A significant association at a query SNP suggests it is the causal polymorphism, or is in strong linkage disequilibrium with the causal site [2-4]. As a class, SNPs represent the most abundant form of genetic variation, with approximately two intermediate frequency SNPs per kilobase in the human genome [5]. Thus, even with some a priori knowledge of a candidate gene region contributing to a disease phenotype, a large number of SNPs need to be genotyped in an association mapping study to ensure one of the genotyped SNPs is causative or is ...
Objectives: Ncf1 polymorphisms leading to low production of reactive oxygen species (ROS) are strongly associated with autoimmune diseases in animal models. The human NCF1 gene is very complex with both functional and non-functional gene copies and genotyping requires assays specific for functional NCF1 genes. We aimed at investigating association and function of the missense single nucleotide polymorphism (SNP), rs201802880 (here denoted NCF1-339) in NCF1 with systemic lupus erythematosus (SLE). Methods: We genotyped the NCF1-339 SNP in 973 Swedish patients with SLE and 1301 controls, using nested PCR and pyrosequencing. ROS production and gene expression of type 1 interferon-regulated genes were measured in isolated cells from subjects with different NCF1-339 genotypes. Results: We found an increased frequency of the NCF1-339 T allele in patients with SLE, 11% compared with 4% in controls, OR 3.0, 95% CI 2.4 to 3.9, p=7.0×10-20. The NCF1-339 T allele reduced extracellular ROS production in ...
Background: Although largely preventable, cardiovascular diseases (CVDs) are the biggest cause of death worldwide. Common complex cardiovascular disorders (e.g., coronary heart disease, hypertonia, or thrombophilia) result from a combination of genetic alterations and environmental factors. Recent advances in the genomics of CVDs have fostered huge expectations about future use of susceptibility variants for prevention, diagnosis, and treatment. Our aim was to summarize the latest developments in the field from a public health perspective focusing on the applicability of data on single nucleotide polymorphisms, through a systematic review of studies from the last decade on genetic risk estimating for common CVDs.Methods: Several keywords were used for searching the PubMed, Embase, CINAHL, and Web of Science databases. Recent advances were summarized and structured according to the main public health domains (prevention, early detection, and treatment) using a framework suggested recently for
Bioinformatics tools: Listing of Single nucleotide polymorphism (SNP) Tools and software. Description of 293 tools - Software, resources, publications, and citations
Allele and genotype frequencies of the two single nucleotide polymorphisms in the VKORC1 gene that are most important for warfarin treatment among Emiratis
Allele and genotype frequencies of the two single nucleotide polymorphisms in the VKORC1 gene that are most important for warfarin treatment among Emiratis
Background and Objectives: Interferon-gamma is an important cytokine, which facilitates immunity against intracellular pathogens. Several factors, including genetic variations of cytokine-producing genes have been shown to influence the progression and severity of Hepatitis C virus (HCV) infection. Methods: Between January and December 2012, 87 HCV-infected individuals and 89 individuals without HCV infection were recruited for the study of Single Nucleotide Polymorphism (SNP) at Interferon Gamma (IFNG) +874 T/A. After extraction of genomic DNA from Peripheral Blood Mononuclear Cells (PBMCs) in blood sample of the individuals, Amplification Refractory Mutation System (ARMS) polymerase chain reaction was performed to evaluate the SNP at this position. Results: The frequency of genotype TA was 62.1% in the HCV-infected group, while it was 47.2% for the control group (p=0.033). However, after adjusting for confounders (including alcohol consumption, drug addiction, transfusion, and tattoos), the genotypes
A tag SNP is a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium that represents a group of SNPs called a haplotype. It is possible to identify genetic variation and association to phenotypes without genotyping every SNP in a chromosomal region. This reduces the expense and time of mapping genome areas associated with disease, since it eliminates the need to study every individual SNP. Tag SNPs are useful in whole-genome SNP association studies in which hundreds of thousands of SNPs across the entire genome are genotyped. Two loci are said to be in linkage equilibrium (LE) if their inheritance is an independent event. If the alleles at those loci are non-randomly inherited then we say that they are at linkage disequilibrium (LD). LD is most commonly caused by physical linkage of genes. When two genes are inherited on the same chromosome, depending on their distance and the likelihood of recombination between the loci they can be at ...
Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC. Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations. Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G|A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P | 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P | 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241
Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005) and genotype (χ2 = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19,p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high
TY - JOUR. T1 - Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins. AU - Donelson Smith, F.. AU - Omar, Mitchell H.. AU - Nygren, Patrick J.. AU - Soughayer, Joseph. AU - Hoshi, Naoto. AU - Lau, Ho Tak. AU - Snyder, Calvin G.. AU - Branon, Tess C.. AU - Ghosh, Debapriya. AU - Langeberg, Lorene K.. AU - Ting, Alice Y.. AU - Santana, Luis Fernando. AU - Ong, Shao En. AU - Navedo, Manuel F. AU - Scott, John D.. PY - 2018/12/4. Y1 - 2018/12/4. N2 - A-kinase anchoring proteins (AKAPs) shape second-messenger signaling responses by constraining protein kinase A (PKA) at precise intracellular locations. A defining feature of AKAPs is a helical region that binds to regulatory subunits (RII) of PKA. Mining patient-derived databases has identified 42 nonsynonymous SNPs in the PKA-anchoring helices of five AKAPs. Solid-phase RII binding assays confirmed that 21 of these amino acid substitutions disrupt PKA anchoring. The most deleterious ...
This track contains information about a subset of the single nucleotide polymorphisms and small insertions and deletions (indels) - collectively Simple Nucleotide Polymorphisms - from dbSNP build 151, available from ftp.ncbi.nlm.nih.gov/snp. Only SNPs that have a minor allele frequency (MAF) of at least 1% and are mapped to a single location in the reference genome assembly are included in this subset. Frequency data are not available for all SNPs, so this subset is incomplete. Allele counts from all submissions that include frequency data are combined when determining MAF, so for example the allele counts from the 1000 Genomes Project and an independent submitter may be combined for the same variant. dbSNP provides download files in the Variant Call Format (VCF) that include a "COMMON" flag in the INFO column. That is determined by a different method, and is generally a superset of the UCSC Common set. dbSNP uses frequency data from the 1000 Genomes Project only, and considers a variant COMMON ...
Transposable elements (TEs) are an important source of genomic variability in eukaryotic genomes. Their activity impacts genome architecture and gene expression and can lead to drastic phenotypic changes. Therefore, identifying TE polymorphisms is key to better understand the link between genotype and phenotype. However, most genotype-to-phenotype analyses have concentrated on single nucleotide polymorphisms as they are easier to reliable detect using short-read data. Many bioinformatic tools have been developed to identify transposon insertions from resequencing data using short reads. Nevertheless, the performance of most of these tools has been tested using simulated insertions, which do not accurately reproduce the complexity of natural insertions. We have overcome this limitation by building a dataset of insertions from the comparison of two high-quality rice genomes, followed by extensive manual curation. This dataset contains validated insertions of two very different types of TEs, LTR
189 sorbs3 TaqMan 5-nuclease assay chemistry provides a fast and simple way to get single nucleotide polymorphism (SNP) genotyping results.
The thiazide-sensitive Na+:Cl- cotransporter is the major salt transport pathway in the distal convoluted tubule of the kidney, and a role of this cotransporter in blood pressure homeostasis has been defined by physiological studies on pressure natriuresis and by its involvement in monogenic diseases that feature arterial hypotension or hypertension. Data base analysis revealed that 135 single nucleotide polymorphisms along the human SLC12A3 gene that encodes the Na+:Cl- cotransporter have been reported. Eight are located within the coding region, and one results in a single amino acid change; the residue glycine at the position 264 is changed to alanine (G264A). This residue is located within the fourth transmembrane domain of the predicted structure. Because Gly-264 is a highly conserved residue, we studied the functional properties of this polymorphism by using in vitro mutagenesis and the heterologous expression system in Xenopus laevis oocytes. G264A resulted in a significant and ...
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes ,99% of SNP variants with a frequency of ,1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies ...
7/7/2008: Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle
Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress ...
43 grik1-as1 TaqMan 5-nuclease assay chemistry provides a fast and simple way to get single nucleotide polymorphism (SNP) genotyping results.
... efficacy and patients prognosis. to predict worse prognosis in patients. Introduction Hepatocellular carcinoma (HCC) is the fifth most common malignancy and is responsible for more than half a million deaths each year, which makes it the third leading cause of cancer deaths worldwide [1]. The severity of HCC and the lack of effective treatment strategies make the disease a major challenge. This disease is usually strongly associated with several risk factors, including chronic hepatitis B computer virus (HBV) an infection, chronic hepatitis C trojan (HCV) an infection, and alcohol mistreatment [2]. The occurrence of HCC provides elevated in Asia and Africa steeply, where HCV and HBV infections are more frequent than in various other continents. HBV infection is normally a challenging ailment in China, where around 93 million folks are HBV providers and 30 million possess chronic hepatitis ...
Endogenous opioids acting at μ-opioid receptors (MOPR) mediate many biological functions. Pharmacological intervention at these receptors has greatly aided in the treatment of acute and chronic pain, in addition to other uses. However, the development of tolerance and dependence has made it difficult to adequately prescribe these therapeutics. A common single nucleotide polymorphism (SNP), A118G, in the MOPR gene can affect opioid function and, consequently, has been suggested to contribute to individual variability in pain management and drug addiction. Investigation into the role of A118G in human disease and treatment response has generated a large number of association studies across various disease states as well as physiological responses. However, characterizing the functional consequences of this SNP and establishing if it causes or contributes to disease phenotypes have been significant challenges. To clarify the functional mechanisms linking the OPRM1 A118G SNP to addiction and analgesia
Incidence and association of TCF7, TCF7L2 single nucleotide polymorphisms in type 1 diabetes mellitus patients of South Tamil Nadu, India
In the present study, we examined the pattern of mtDNA mutations in histologically negative margins and tumors obtained from 50 recurrent HNSCC patients by sequencing the entire mitochondrial genome on the Affymetrix Mitochip 2.0 sequencing platform (6-8). To our knowledge, this is the first report of the scrutiny of mtDNA mutation pattern in normal surgical margins of HNSCC patients. This high-throughput mtDNA resequencing platform overcomes conventional DNA sequencing method as reliable mutation detection is possible (6, 7). Stringent criteria were followed and appropriate databases were used to classify every single mtDNA sequence variant, considering the recent findings of erroneous reporting of mtDNA mutation in different cancers (13-17). Based on the standard data interpretation criterion, we detected both somatic and germ line mtDNA sequence variants in these patients and also confirm that the resultant sequence variations are not known single nucleotide polymorphisms in different ...
IRF5 is a transcription factor that plays a crucial role in mediating both virus- and TLR-induced type I IFN and proinflammatory cytokine expression (19-24). Numerous genetic association studies have implicated IRF5 in the pathogenesis of a variety of autoimmune diseases, such as systemic lupus erythematosus (SLE), due to IRF5 polymorphisms that were found to be associated with disease susceptibility (reviewed in Refs. 49, 50). We recently demonstrated that IRF5 expression is significantly elevated in SLE patients compared with healthy donors and that upregulation of both IRF5 transcript and protein levels was associated with an SLE risk haplotype (51). Current data indicate that single nucleotide polymorphisms in the IRF5 gene may define isoform expression; for instance, the risk alleles of single nucleotide polymorphism rs10488631 were highly associated with elevated expression of IRF5 from noncoding exon 1c corresponding to IRF5 V3 (51). Support has been building around the hypothesis that ...
Abstract. The traditional method for creating a gene score to predict a given outcome is to use the most statistically significant single nucleotide polymorphisms (SNPs) from all SNPs which were tested. There are several disadvantages of this approach such as excluding SNPs that do not have strong single effects when tested on their own but do have strong joint effects when tested together with other SNPs. The interpretation of results from the traditional gene score may lack biological insight since the functional unit of interest is often the gene, not the single SNP. In this paper we present a new gene scoring method, which overcomes these problems as it generates a gene score for each gene, and the total gene score for all the genes available. First, we calculate a gene score for each gene and second, we test the association between this gene score and the outcome of interest (i.e. trait). Only the gene scores which are significantly associated with the outcome after multiple testing ...
The present study investigated basic statistics for biometric traits as well as non-genetic factors that may affect these traits in the Moghani breed of sheep. The data-set was computed by using biometric records of the Moghani sheep breeding and raising station over a period of 15 years (1996 to 2012). Year of birth, month of birth, birth type and lambs sex and dam permanent environment were considered as the non-genetic factors. The studied biometric traits were: height at withers (HW), height at rump (HR), body length (BL), heart girth (HG) and leg circumference (LC). Least square means (cm) ± standard error were 69.8 ± 4.1, 69.7 ± 4.2, 50.2 ± 4.6, 85.9 ± 8.2 and 29.0 ± 5.4 for HW, HR, BL, HG and LC, respectively. All traits were affected significantly (P|0.05) by the fixed effect of year of birth. The lambs sex had a significant effect (P|0.001) on the investigated traits except HG. The traits were affected significantly (P|0.001) by the birth type and month of birth. The maternal permanent
Background: Using array techniques, it was recently shown that about 10% of patients with mental retardation of unknown origin harbour cryptic chromosomal aneusomies. However, data analysis is currently not standardised and little is known about its sensitivity and specificity.. Methods: We have developed an electronic data analysis tool for gene-mapping SNP arrays, a software tool that we call Copy Number Variation Finder (CNVF). Using CNVF, we analysed 104 unselected patients with mental retardation of unknown origin with a genechip mapping 100K SNP array and established an optimised set of analysis parameters.. Results: We detected deletions as small as 20 kb when covered by at least three single-nucleotide polymorphisms (SNPs) and duplications as small as 150 kb when covered by at least six SNPs, with only one false-positive signal in six patients. In 9.1% of patients, we detected apparently disease-causing or de novo aberrations ranging in size from 0.4 to 14 Mb. Morphological anomalies in ...
DESCRIPTION (provided by applicant): While there is no doubt smoking is a direct causative factor underlying the development of lung cancer, not every smoker develops lung cancer. In fact, only 10-15% of smokers develop this disease, indicating that otherfactors make certain individuals more susceptible to cancer. A number of single nucleotide polymorphisms are known to correlate with the development of lung cancer, but the underlying genes responsible for this association are not always clear. Nor is theimpact of any one of these polymorphisms by themselves known to be highly significant. Indeed, as of yet there are no known genes that have been convincingly associated with lung cancer. Our research has focused on the SWI/SNF complex, which controls and regulates gene expression for a number of proteins and signaling pathways that have anticancer functions. We have found that the inactivation of this complex-particularly via loss of its key catalytic subunit, BRM-promotes cancer development. ...
Glucagon-like Peptide-1 (GLP-1) is an important incretin hormone which acts as a powerful insulin secretagogue. Defects in GLP-1 synthesis and secretion are thought to be part of the pathogenesis of type 2 diabetes. Furthermore GLP-1 based therapy is an important part of the therapeutic armamentarium for the treatment of type 2 diabetes. The GLP-1 receptor (GLP1R) is the principal site of action of GLP-1 and GLP-1 receptor agonists like exenatide and liraglutide. The gene coding for this receptor, GLP1R, is highly polymorphic and contains numerous non-synonymous Single Nucleotide Polymorphisms (nsSNPs) which could potentially alter response to endogenous or exogenous GLP-1 or GLP-1R agonists. Indeed there is some in vitro data to support this concept. We propose to utilize a hyperglycemic clamp to test the insulin secretory response to infused GLP-1 in healthy volunteers to determine the effect of genetic variation in GLP1R on response to GLP-1 ...
Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called HapMap 3, includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of ≤5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome ...
Our knowledge and understanding of the genetic influences on common disease risk and therapeutic efficacy of pharmacologic agents has increased dramatically in the past decade. Since the completion of the Human Genome Project in 2003, genomics research has exploded, yielding an evergrowing number of genomic variants that are associated with an individuals risk for a disease or their response to a medication. This began in earnest with the development of high-throughput genotyping technology and the subsequent success of genome-wide association studies (GWASs) in identifying large numbers of genomic variants with potential clinical utility. The most common genetic variations among people are single-nucleotide polymorphisms (SNPs) ("snips"). Each SNP denotes a difference in a single nucleotide. For example, in a stretch of DNA, a SNP may replace the nucleotide adenine (A) with guanine (G). A phenotype is an observable or measurable characteristic of an individual, such as height, weight, blood ...
The possibility that single nucleotide polymorphisms (SNPs) may be useful in identifying candidate disease genes and individuals at risk of disease has led to extensive projects aimed at discovery and organization of SNPs into databases. As of February 2001, ,2 million candidate SNPs were available in the public dbSNP databases (Sachidanandam et al., 2001) suggesting that if the promise of polymorphism analysis is realized, we are entering into an "era of personalized medicine" (Kwok and Gu, 1999). Far less has been done to functionally characterize polymorphisms in coding regions. The present study aimed to find and phenotypically characterize COX-2 polymorphisms that might be associated with disease or with individual responses to drug therapies.. Three observed SNPs, C-162G, T10G, and V511A, were also identified in other SNP discovery projects (P. J. Oefner, unpublished data; A.Halushka et al., 1999) and are present in the National Center for Biotechnology Information dbSNP database ...
Single nucleotide polymorphism (SNP) genotyping assays normally give rise to certain percents of no-calls; the problem becomes severe when the target organisms, such as cattle, do not have a high resolution genomic sequence. Missing SNP genotypes, when related to target traits, would confound downstream data analyses such as genome-wide association studies (GWAS). Existing methods for recovering the missing values are successful to some extent - either accurate but not fast enough or fast but not accurate enough. To a target missing genotype, we take only the SNP loci within a genetic distance vicinity and only the samples within a similarity vicinity into our local imputation process. For missing genotype imputation, the comparative performance evaluations through extensive simulation studies using real human and cattle genotype datasets demonstrated that our nearest neighbor based local imputation method was one of the most efficient methods, and outperformed existing methods except the time-consuming
Liang C, Medical science monitor : international medical journal of experimental and clinical research, BACKGROUND CCL11 is an important inflammatory cytokine associated with inflammation-related diseases such as atherosclerosis and stroke. The aim of th
DescriptionIn analyzing human genetic disorders, association analysis is one of the most commonly used approaches. However, there are challenges with association analysis, including differential misclassification in data that inflates the false-positive rate. In this thesis, I present a new statistical method for testing the association between disease phenotypes and multiple single nucleotide polymorphisms (SNPs). This method uses next-generation sequencing (NGS) raw data and is robust to sequencing differential misclassification. By incorporating expectation-maximization (EM) algorithm, this method computes the test statistic and estimates important parameters of the model, including misclassification. By performing simulation studies, I report that this method maintains correct type I error rates and may obtain high statistical power. ...
With the purpose of understanding relationship between phenotypic and genetic variations in cultivated tomato, single nucleotide polymorphism (SNP) markers within the whole genome of cultivated tomato were developed and genome-wide association studies (GWAS) were performed. attributes, with SNP loci located near genes which were reported as candidates for these traits previously. This research demonstrates that appealing loci could be determined by executing GWAS with a lot of SNPs extracted from re-sequencing evaluation. = 2= 24) and a comparatively small genome (950 Mb). Lately, the whole-genome series of tomato was released.12 Furthermore, Hirakawa assembly of genome re-sequencing and sequences analyses of genomes of many microorganisms.14,15 In such re-sequencing analysis, series reads from the complete genome are mapped onto the guide genome to recognize nucleotide variations, including single nucleotide polymorphisms (SNPs) and insertions/deletions (indels).14 A great deal of nucleotide ...
Cancer predisposition by the cooperation of genetic variants, such as single nucleotide polymorphisms (SNPs), may be of much greater significance to public health than previously appreciated. Functional polymorphisms are genetic variants that alter gene function. Meta-analyses associate many functional polymorphisms with cancer risk. The MDM2 SNP309G allele is a cancer-associated functional polymorphism positioned in the MDM2 P2 promoter that enhances transcription factor SP1 binding, resulting in elevated levels of MDM2 concomitant with decreased p53 tumor-suppressor activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP on tumor development. We examined the impact of SNP309 on cancer risk in response to environmental factors by treating SNP309 mice with ionizing radiation, UVB, or Benzo(a)pyrene. The results show that SNP309G cooperates with ionizing radiation to exacerbate tumor development.
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Genome-wide association studies (GWAS) have emerged as an important tool for discovering regions of the genome that harbor genetic variants that confer risk for different types of cancers. The success of GWAS has been a consequence of the convergence of new technologies that can genotype hundreds of thousands of common single nucleotide polymorphism (SNP) markers together with comprehensive annotation of genetic variation. This approach has provided the opportunity to scan across the genome in a sufficiently set of cases and controls without a set of prior hypotheses in search of susceptibility alleles with low effect sizes. So far, susceptibility alleles discovered thus far are common, namely, with a frequency in one or more population of greater than 5% and each allele confers a small contribution to the overall risk for the disease. In prostate cancer, there could be more than 35 distinct regions harboring common susceptibility alleles identified by GWAS whereas in lung cancer, a disease ...
TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3UTR of TNFAIP2 and gastric cancer risk in a US population.We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T,C, rs710100 G,A, rs1052912 G,A and rs1052823 G,T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk.The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09-3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric ...
A subgroup of women enrolled in the Pumwani sex worker cohort remain seronegative and PCR negative for human immunodeficiency virus type 1 despite repeated exposure through high-risk sex work. Studies have shown that polymorphisms of genes involved in antigen presentation and viral restriction factors are associated with resistance to HIV infection. To discover other possible genetic factors underlying this HIV-resistant phenotype, we conducted an exploratory nonbiased, low-resolution, genome-wide single-nucleotide polymorphism (SNP) analysis comparing 60 HIV-resistant women to 48 HIV-infected controls. The SNP minor allele rs1552896, in an intron of FREM1, was significantly associated with the resistant phenotype (P = 1.68 × 10−5; adjusted P = 2.37 × 10−4; odds ratio [OR], 9.51; 95% confidence interval [CI], 2.82 to 32.05). We expanded the sample size by genotyping rs1552896 in the Pumwani cohort and comparing 114 HIV-resistant women to 609 HIV-infected controls and confirmed the ...
With the purpose of understanding relationship between phenotypic and genetic variations in cultivated tomato, single nucleotide polymorphism (SNP) markers within the whole genome of cultivated tomato were developed and genome-wide association studies (GWAS) were performed. attributes, with SNP loci located near genes which were reported as candidates for these traits previously. This research demonstrates that appealing loci could be determined by executing GWAS with a lot of SNPs extracted from re-sequencing evaluation. = 2= 24) and a comparatively small genome (950 Mb). Lately, the whole-genome series of tomato was released.12 Furthermore, Hirakawa assembly of genome re-sequencing and sequences analyses of genomes of many microorganisms.14,15 In such re-sequencing analysis, series reads from the complete genome are mapped onto the guide genome to recognize nucleotide variations, including single nucleotide polymorphisms (SNPs) and insertions/deletions (indels).14 A great deal of nucleotide ...
MyJournals.org - Science - Correlation of drug resistance with single nucleotide variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate of M. tuberculosis (BMC Microbiology)
CD Genomics provides whole-genome SNP genotyping by using both microarray technologies and high-throughput next-generation sequencing (NGS), enabling genome-wide discoveries and screening of the SNP loci.