Allele Of SNP Research Articles

Vitamin D receptor genotype influences risk of upper respiratory infection.

SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, P for trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (P for trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.

Relevance of polymorphisms in MC4R and BDNF in short normal stature

BackgroundVariation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this common condition.MethodsWe analyzed the coding regions of LEP, MC4R, MRAP2 and BDNF in 185 children with SNS (height < 5th percentile) to search for non-synonymous and frameshift variants. For association studies (two-sided χ2-tests) population-based data sets (ExAC, EVS and KORA) were used. Cyclic AMP accumulation, cell surface expression, central expression and MAP kinase activation were assayed in vitro to determine the functional implications of identified variants.ResultsWe detected eleven variants predicted to be protein-altering, four in MC4R, four in BDNF, and three in MRAP2. No variants were found in LEP. In vitro analysis implied reduced function for the MC4R variant p.Met215Ile. Loss-of-function is contrary to expectations based on obesity studies, and thus does not support that this variant is relevant for SNS. The minor SNP alleles at MC4R p.Val103Ile and BDNF p.Val66Met were nominally associated with SNS.ConclusionTaken together, although genes of the leptinergic-melanocortinergic system are important for normal growth, our data do not support the involvement of rare mutations in LEP, MC4R, MRAP2 or BDNF in short normal stature.

DRD2 is associated with fear in some dog breeds

Abstract Behavioral problems occur frequently in dogs and represent a significant threat to dog welfare. Anxiety, phobias, and fears comprise most of the canine behavioral conditions. The identification of an association between specific behavioral phenotypes and genetic variants of candidate genes would be a valuable tool in selection for dogs less susceptible to anxiety and fear, which may improve animal welfare. The DRD2 gene encodes the dopamine receptor 2. In this study, we found 8 SNPs in the DRD2 gene of the Havanese, a breed that shows large variation in a behavioral phenotype that manifests itself as a tendency to react fearfully by withdrawing in social situations. Significant associations were detected between 2 SNPs in exon 2 of the DRD2 gene and increased social fear in Havanese dogs (n = 158), as evaluated through observation by an external evaluator (respective allelic odds ratio: 4.35, 4.07) and through owner questionnaires (respective allelic odds ratio: 1.96, 2.2). Because different types of fear-related behavioral disorders commonly co-occur, the SNPs in exon 2 were also investigated for possible association to noise reactivity in 5 breeds: Havanese (n = 121), collie (n = 94), Irish soft-coated wheaten terrier (n = 44), Nova Scotia duck tolling retriever (n = 33), and standard poodle (n = 29). Significant associations were detected between SNPs in exon 2 of the DRD2 gene and noise reactivity in the Irish soft-coated wheaten terrier (respective allelic odds ratio: 2.64, 2.88) and collie (allelic odds ratio: 3.03). The same SNP alleles were associated with the beneficial phenotypes in the 3 breeds.

Moderating effect of PLIN4 genetic variant on impulsivity traits in 5-year-old-children born small for gestational age

Poor fetal growth is associated with long-term behavioral, metabolic and psychiatric alterations, including impulsivity, insulin resistance, and mood disorders. However, the consumption of omega-3 polyunsaturated fatty acid (n-3 PUFA) seems to be protective for this population, improving inhibitory control and behavioral reactivity. We investigated whether the presence of the A allele of rs8887 SNP (PLIN4 gene), known to be associated with increased sensitivity to the consumption of n-3 PUFAs, interacts with fetal growth influencing inhibitory control. 152 five-year-old children were genotyped and performed the Stop Signal Task (SSRT). There was a significant interaction between birth weight and the presence of the A allele on SSRT performance, in which lower birth weight associated with poorer inhibitory control only in non-carriers. These results suggest that a higher responsiveness to n-3 PUFAS protects small for gestational age children from developing poor response inhibition, highlighting that optimizing n-3 PUFA intake may benefit this population.

Two-person DNA mixture interpretation based on a novel set of SNP-STR markers

Autosomal short tandem repeats (STR) markers analysed by PCR and capillary electrophoresis (CE) represent the gold-standard for forensic DNA analysis. With the improved sensitivity of detection equipment, a larger number of mixed DNA profiles can be obtained from trace amounts of DNA that conventionally used to appear as a single source. More specifically, two-source DNA mixtures, comprising the victim’s and the perpetrator’s DNAs, are often encountered in forensic casework, where the victim’s DNA represents a major component of the mixture. Unfortunately, unbalanced two-person DNA mixtures with a ratio larger than 20:1 (here we have named this kind of mixture extremely unbalanced DNA mixture) provide limited information on the minor component. Although the development of probabilistic software has made interpretation of results from mixed DNA easier, high mixture ratios lead to an uninformative likelihood ratio (LR), considering the minor component. Therefore, a technique that can be performed on the conventional CE platform, while enhancing the ability to detect minor DNA in extremely unbalanced DNA mixtures, may be very useful in forensic casework. Our previous research has reported that SNP-STRs, in conjunction with a PCR technique based on amplification refractory mutation system (ARMS), can be used to resolve extremely unbalanced two-person DNA mixtures. To further explore the capacity of SNP-STR markers to help analyse such DNA mixtures, we developed 11 novel SNP-STR markers. The ARMS-based PCR was then used to design allele-specific primers, where each primer targeted one SNP allele located in the flanking region of the tandem repeats. This method allowed primers to specifically and selectively amplify minor DNA without interference from DNA of the major component because the selected SNP allele was not shared with the major contributor. A survey of the selected 11 SNP-STRs in a southwest Chinese Han population showed high levels of polymorphism. Assays on two-person DNA mixtures showed that all the allele-specific primers could target minor DNA even when the amount of major DNA was a 100-fold higher. Therefore, this novel set of SNP-STR markers provides an alternative method for the analysis of extremely unbalanced two-person DNA mixtures.

Allele distribution and testing for association between an oxygen dependent degradation domain SNP in EPAS1 and pulmonary arterial pressures in yearling Angus cattle

At altitudes >1500 m, measurements of mean pulmonary arterial pressures (mPAP; mmHg) are a measure of pulmonary hypertension (PH) in cattle. Genotypes of a G/A single nucleotide polymorphism (SNP; rs208684340) in the endothelial PAS domain protein 1 (EPAS1) gene were determined for mPAP categories (low, moderate, high) on Angus cattle. The A allele of this SNP was postulated to be associated with altitude-induced PH. The first objective was to estimate allele and genotypic frequencies in Angus cattle at high- (elevation 1850 to 2800 m) and low-altitude (elevation 91 to 1192 m) ranches (n = 118; random sample of 1275). Percent of cattle at these low elevation ranches with genotypes G/G, G/A, and A/A were 64.4, 33.9, and 1.7%, respectively, and a minor allele frequency (MAF; A allele) of 18.6%. Bulls, steers, and heifers (n = 691) from 4 high-altitude Angus herds in Colorado and Wyoming were genotyped. Percent of cattle with genotypes G/G, G/A, and A/A were 48.6, 34.3, and 17.1%, respectively, with a MAF of 34.2%. Average mPAP was 40.5 ± 8.8 mmHg. Low, moderate, and high-mPAP category MAF were similar (χ2 = 3.03; P = 0.22), with values of 35.4, 31.0, and 37.8%, respectively. Additionally we sought to evaluate the genotype-to-phenotype association of this SNP with mPAP phenotypes (n = 532) from the Colorado State University Beef Improvement Center (elevation 2150 m) Angus herd. Linear mixed model analysis suggested genotype was not a predictor (P = 0.61) of mPAP. Results do not suggest the A allele of SNP in EPAS1 is associated with high altitude-induced PH in yearling Angus cattle.

Assessment of genetic diversity in Egyptian barley (Hordeum vulgare L.) genotypes using SSR and SNP markers

A barley core collection can be studied extensively and the derived information can be used to identify loci/genes for the genetic improvement of quantitative and qualitative traits. To assess genetic diversity, allelic variation and population structure of Egyptian barley, 134 barley genotypes collected from a different region along with 19 cultivated genotypes obtained from of the Egyptian Agricultural Research Center. All genotypes were analyzed with 261 polymorphic SSR and SNP alleles. The mean number of alleles per locus was 4 and PIC was 0.49, while the level of genetic diversity was 0.55 ranging from 0.03 to 0.82. The genotypes were assigned to three subpopulations that were consistent with their origins. The genetic variation within population was higher (51%) than among population at the molecular levels (FST = 0.491 when P < 0.10). The level of polymorphic variation was highest in subpopulations-II, due to collected from different regions with different ear-types thus, expected to contain more diversity than local genotypes in subpopulations-I and subpopulations-III. The structured study found that the 153 barley genotypes are in harmony with clustering approaches using the SSR and SNP genotypic data in a neighbor-joining tree and principal components analysis, which identified three subpopulations. These results demonstrated genetic diversity among the Egyptian barley genotypes can be applied to suggest approaches, such as association analysis, classical mapping population development, and parental line selection in breeding programs. Therefore, it is necessary to use the exotic genotypes as the genetic resources for developing new barley cultivars in Egypt.

PO-054 Common genetic variants at the breast cancer risk region 2Q35 map to putative IGFbp5 enhancers

IntroductionGenome-wide association studies (GWAS) have identified over 100 independently-associated regions of the genome with germline variants that modulate risk of developing breast cancer. Most signals map to non-coding regions of the genome and are thought to act at the level of gene regulation. Whilst GWAS are instrumental in highlighting regions of interest, it is important to identify the causal variant(s) at each locus and the mechanisms by which they influence risk.Material and methodsWe investigated the 2q35 breast cancer risk locus using two complementary methods. The first method involved selecting potentially causal variants based primarily on breast relevant functional data (Capture Hi-C, ChIP-seq, DNase-seq, GRO-seq) The second method involved conventional fine-mapping of case-control samples, to generate a short list of potentially causal variants that cannot be excluded on statistical grounds alone followed by intersection of the same breast-relevant functional data.Results and discussionsThe two methods identify distinct subsets of putative causal SNPs mapping to ERα/FOXA1 enhancer-like elements targeting the IGFBP5 gene promoter, a gene known to play a role in breast development. We confirmed enhancer status by performing luciferase reporter assays containing each of the regions of interest; furthermore, by introducing minor SNP alleles we identified a subset of SNPs that modulate strength of enhancer activity. ChIP-seq in heterozygous cell lines also confirms an allelic preference in enhancer binding. We are now using CRISPR/Cas9-based systems to investigate the regions of interest through perturbation studies, and generating isogenic cell lines to further investigate SNP effects on transcription factor binding, chromosome conformation and gene expression.ConclusionThe 2q35 breast cancer risk locus consists of three independent risk-associated signals. Statistical and functional approaches to variant prioritisation are complementary, identifying largely overlapping but distinct sets of candidate causal variants in putative regulatory elements (PREs). Subsequent functional investigation suggests these genetic variants may modulate the strength of these PREs; however, further investigation in isogenic cell lines is required.

Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South-Khorasan of Iran.

Colorectal cancer (CRC) is a global public health problem. Despite the major milestone in early diagnosis and treatment of colorectal cancer, the prevalence of CRC rates is still rising. The etiology of CRC is still unknown but we know CRC is influenced by both of environment and genetic factors. In this study, we aimed to elucidate the role of vitamin D receptor gene polymorphic regions; FokI and TaqI single nucleotide polymorphisms, in increasing the risk of colorectal cancer in Birjand population. One hundred patients with CRC and 100 healthy controls recruited to the study. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) method technique for all individuals. There were statistically significant differences between ff genotype and f allele of FokI SNP in case and control groups. Our results manifested positive correlation between ff genotype and f allele of FokI SNP with colorectal cancer predisposition (P = 0.035, P = 0.0001 respectively) in South Khorasan population. The present study showed that FokI polymorphism but not TaqI polymorphism may contribute to CRC susceptibility. In addition, ff genotype of FokI polymorphism was associated with CRC risk.

Temperature gradient affects differentiation of gene expression and SNP allele frequencies in the dominant Lake Baikal zooplankton species.

Local adaptation and phenotypic plasticity are main mechanisms of organisms' resilience in changing environments. Both are affected by gene flow and are expected to be weak in zooplankton populations inhabiting large continuous water bodies and strongly affected by currents. Lake Baikal, the deepest and one of the coldest lakes on Earth, experienced epilimnion temperature increase during the last 100years, exposing Baikal's zooplankton to novel selective pressures. We obtained a partial transcriptome of Epischura baikalensis (Copepoda: Calanoida), the dominant component of Baikal's zooplankton, and estimated SNP allele frequencies and transcript abundances in samples from regions of Baikal that differ in multiyear average surface temperatures. The strongest signal in both SNP and transcript abundance differentiation is the SW-NE gradient along the 600+km long axis of the lake, suggesting isolation by distance. SNP differentiation is stronger for nonsynonymous than synonymous SNPs and is paralleled by differential survival during a laboratory exposure to increased temperature, indicating directional selection operating on the temperature gradient. Transcript abundance, generally collinear with the SNP differentiation, shows samples from the warmest, less deep location clustering together with the southernmost samples. Differential expression is more frequent among transcripts orthologous to candidate thermal response genes previously identified in model arthropods, including genes encoding cytoskeleton proteins, heat-shock proteins, proteases, enzymes of central energy metabolism, lipid and antioxidant pathways. We conclude that the pivotal endemic zooplankton species in Lake Baikal exists under temperature-mediated selection and possesses both genetic variation and plasticity to respond to novel temperature-related environmental pressures.

Evaluation of ATG5 polymorphisms in Italian patients with systemic lupus erythematosus: contribution to disease susceptibility and clinical phenotypes.

Systemic lupus erythematosus (SLE) is a common heterogeneous autoimmune disease that is caused by the involvement both of genetic and environmental factors. There is evidence that autophagy is involved in several aspects of SLE pathogenesis. In particular, polymorphisms in the ATG5 gene have been observed to be associated with disease susceptibility. Our aim was to verify if ATG5 polymorphisms are involved in the susceptibility to disease and its clinical phenotypes in an Italian cohort of SLE patients. This study involved 315 SLE patients and 265 healthy controls. Three polymorphisms in the ATG5 gene (rs573775, rs6568431 and rs2245214) were investigated by allelic discrimination assay. A case-control association study, a genotype/phenotype correlation analysis and a haplotype study were performed. Moreover, an expression study was conducted in peripheral blood mononuclear cells from 15 SLE patients to verify a possible effect of the three SNPs on the expression of ATG5. Among the three investigated SNPs, only the rs573775 SNP was significantly associated with disease susceptibility with the variant allele conferring a higher risk of developing SLE (OR = 1.50, p = 0.018 and OR = 1.48, p = 0.007 at the genotypic and allelic level, respectively). The variant allele of rs6568431 SNP was more present in patients with anemia (OR = 1.86, p = 0.009) and renal involvement (OR = 1.63, p = 0.06), while the variant allele of rs2245214 SNP was significantly associated with a higher risk of producing anti-DNA autoantibodies (OR = 1.66, p = 0.04). Carriers of the rs6568431 variant allele showed higher messenger RNA levels compared to the carriers of the wild-type allele, suggesting also a potential variant allele dose-dependent effect on gene expression. In conclusion, our study confirms a role for ATG5 polymorphisms both in disease susceptibility and in the modulation of clinical phenotypes in an Italian SLE cohort. These results further suggest that genetic variations in autophagy genes could play a role in autoimmune diseases susceptibility and are worth further investigation.

Dynamic demethylation of the IL2RA promoter during in vitro CD4+ T cell activation in association with IL2RA expression

ABSTRACTIL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+ T cells in response to various stimuli and is constitutive in regulatory T cells (Tregs). We selected for our study 18 CpGs located within cognate regulatory regions of the IL2RA locus and characterized their methylation in naive, regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502) show dynamic, active demethylation during the in vitro activation of naive CD4+ T cells. Demethylation of these CpGs correlates with appearance of IL2RA protein at the cell surface. We found no influence of cis located SNP alleles upon CpG methylation. Treg cells show constitutive demethylation at all studied CpGs. Methylation of 9/18 CpGs, including CpG +3502, decreases with age. Our data thus identify CpG +3502 and a few other CpGs at the IL2RA locus as coordinated epigenetic regulators of IL2RA expression in CD4+ T cells. This may contribute to unravel how the IL2RA locus can be involved in immune physiology and pathology.

Association of Tolllike receptor2 and 9 gene variants with pulmonary tuberculosis: exploration in a northern Indian population.

Tuberculosis (TB) is a disease of global importance. There is an increasing recognition of the role of Toll like receptors, important pattern recognition receptors of host immune system, in determining the susceptibility or resistance to TB in various populations. In an attempt to examine the importance of Toll like receptors in immune response to Mycobacterium tuberculosis infection, we explored two variants each of TLR2 and TLR9 in a population residing in Uttar Pradesh, India. Genotyping was performed to detect -196 to -174 del polymorphism and G2258A SNP (Arg753Gln, rs5743708) in TLR2 gene and -T1237C (rs5743836) and G2848A (rs352140) SNP in TLR9 gene in patients with pulmonary TB and healthy controls. The A allele of G2848A SNP in TLR9 gene was found with a marginally higher frequency among TB patients as compared to healthy controls, suggesting that A allele at position 2848 of TLR9 gene may be associated with susceptibility to TB in North Indian population [p = 0.05, Mantel-Haenszel OR = 1.34, 95% CI (1.0-1.82)].

Variation in the TEK gene is not associated with asthma but with allergic conjunctivitis.

The Tie2 receptor is an important player in angiogenesis. The Tie2 mRNA and protein are abundantly expressed in the lungs and the associated pathway also has an important role in the development and function of the eye. Tie2 is encoded by the TEK gene in humans. Recently, variations in the TEK gene have been found associated with asthma. The objective of the present study was to investigate whether variations in the TEK gene influenced the susceptibility to pediatric asthma and/or associated phenotypes like GINA status, viral- or exercise-induced asthma, allergic asthma, indoor, outdoor, inhalative allergies, IgE and eosonophil levels, allergic rhinitis and allergic conjunctivitis. Three single nucleotide polymorphisms (SNPs, rs3780315, rs581724 and rs7876024) in the TEK gene were genotyped in 1189 unrelated individuals, out of which 435 were asthmatic children and 754 healthy controls. Different types of asthma, allergies and co-morbidities were defined in 320 patients. Among the fully phenotyped 320 asthmatic patients 178 (55.6%) also had allergic rhinitis and 100 (31.3%) had conjunctivitis. Among the rhinitis patients 98 (55.1%) also had conjunctivitis. Two patients had conjunctivitis without rhinitis. The genotyped SNPs showed no association with asthma. However, SNP rs581724 was significantly associated with allergic conjunctivitis in a recessive way (p=0.007; OR=2.3 (1.3-4.4)) within the asthmatic population. The risk remained significant when the whole population (asthmatics and healthy controls) was included in the calculation (p = 0.003; OR = 2.1 (1.3-3.6)). The minor allele of the rs581724 SNP which is associated with the increased risk to conjunctivitis is also associated with reduced Tie2 expression. There was a significant association between SNP rs581724 and the occurrence of allergic conjunctivitis in asthmatic children. If additional studies can confirm the role of the Tie2 pathway in allergic conjunctivitis, it can be a potential novel therapeutic target in the disease.

Application of droplet digital PCR for prenatal screening of Down syndrome

Background: This study was proposed to explore the feasibility of droplet digital PCR (ddPCR) analysis for non-invasive prenatal diagnosis of Down syndrome. Materials and Methods: The authors studied maternal plasma samples from 465 pregnant women carrying euploid and trisomy 21 (T21) fetuses. A methylation-sensitive restriction endonuclease, BstUI, was used to digest the hypomethylated holocarboxylase synthetase (HLCS) gene. The authors quantified digestion-resistant HLCS gene on chromosome 21 and fetal-specific rs6636 SNP allele on chromosome 14 by droplet digital PCR analysis. Maternal plasma DNA analysis was performed by comparing the ratio of hypermethylated HLCS to fetal-specific rs6636 SNP allele between two groups. Results: Using a rs6636 SNP allele on chromosome 14 as the reference marker, the authors analyzed 78 euploid and 28 T21 plasma samples. The ratios of the numbers of positive hypermethylated HLCS and the fetal-specific C allele in the euploid and T21 samples were significantly different ( p p Conclusions: The study demonstrated that ddPCR approach can be applied for prenatal screening of trisomy 21.

A method for determining haploid and triploid genotypes and their association with vascular phenotypes in Williams syndrome and 7q11.23 duplication syndrome

BackgroundWilliams syndrome ([WS], 7q11.23 hemideletion) and 7q11.23 duplication syndrome (Dup7) show contrasting syndromic symptoms. However, within each group there is considerable interindividual variability in the degree to which these phenotypes are expressed. Though software exists to identify areas of copy number variation (CNV) from commonly-available SNP-chip data, this software does not provide non-diploid genotypes in CNV regions. Here, we describe a method for identifying haploid and triploid genotypes in CNV regions, and then, as a proof-of-concept for applying this information to explain clinical variability, we test for genotype-phenotype associations.MethodsBlood samples for 25 individuals with WS and 13 individuals with Dup7 were genotyped with Illumina-HumanOmni5M SNP-chips. PennCNV and in-house code were used to make genotype calls for each SNP in the 7q11.23 locus. We tested for association between the presence of aortic arteriopathy and genotypes of the remaining (haploid in WS) or duplicated (triploid in Dup7) alleles.ResultsHaploid calls in the 7q11.23 region were made for 99.0% of SNPs in the WS group, and triploid calls for 98.8% of SNPs in those with Dup7. The G allele of SNP rs2528795 in the ELN gene was associated with aortic stenosis in WS participants (p < 0.0049) while the A allele of the same SNP was associated with aortic dilation in Dup7.ConclusionsCommonly available SNP-chip information can be used to make haploid and triploid calls in individuals with CNVs and then to relate variability in specific genes to variability in syndromic phenotypes, as demonstrated here using aortic arteriopathy. This work sets the stage for similar genotype-phenotype analyses in CNVs where phenotypes may be more complex and/or where there is less information about genetic mechanisms.

POLARIS: Polygenic LD-adjusted risk score approach for set-based analysis of GWAS data.

ABSTRACTPolygenic risk scores (PRSs) are a method to summarize the additive trait variance captured by a set of SNPs, and can increase the power of set‐based analyses by leveraging public genome‐wide association study (GWAS) datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk for the same or different phenotype estimated from independent data. We propose the application of PRSs as a set‐based method with an additional component of adjustment for linkage disequilibrium (LD), with potential extension of the PRS approach to analyze biologically meaningful SNP sets. We call this method POLARIS: POlygenic Ld‐Adjusted RIsk Score. POLARIS identifies the LD structure of SNPs using spectral decomposition of the SNP correlation matrix and replaces the individuals' SNP allele counts with LD‐adjusted dosages. Using a raw genotype dataset together with SNP effect sizes from a second independent dataset, POLARIS can be used for set‐based analysis. MAGMA is an alternative set‐based approach employing principal component analysis to account for LD between markers in a raw genotype dataset. We used simulations, both with simple constructed and real LD‐structure, to compare the power of these methods. POLARIS shows more power than MAGMA applied to the raw genotype dataset only, but less or comparable power to combined analysis of both datasets. POLARIS has the advantages that it produces a risk score per person per set using all available SNPs, and aims to increase power by leveraging the effect sizes from the discovery set in a self‐contained test of association in the test dataset.

Sensitive mutant detection by concentrating mutant DNA with allele-specific capture and its application to analysis of contaminated grains in rice.

We developed a method for detection of mutants in a large number of plants, and found this method to be applicable to detection of a mutant allele at a concentration of 1/1000. Many techniques for SNP analysis have been developed, but most of these techniques are not so sensitive to be used for detection of mutants in a large number of plants. Although some highly sensitive methods of SNP analysis have been reported, they are costly. In the present study, a method for concentrating mutant DNA was examined for sensitive detection of an SNP allele in a bulked DNA sample. PCR products of mutant alleles were captured by biotin-labeled oligonucleotide conjugated with streptavidin-coated magnetic beads. By repeated captures of each strand and combining both strands, mutant alleles with a concentration of 1/1000 in wild-type alleles were detectable by CAPS or dCAPS analysis. Indirect capture of a mutant allele was possible, but efficiency was slightly lower than that of the direct capture. The developed method was applied to detection of contamination of rice grains by grains of a different cultivar. Possible applications of this method are discussed.

The CD14 (\u2212159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult Caucasians.

Association between BACE1 gene polymorphisms and focal seizures in a Chinese Han population.

Background:Beta-secretase 1 (BACE1) is attracting increasing attention for its vital role in pathogenesis of many neuropsychiatric disorders and many studies also have indicated BACE1 as a possible risk factor for seizures, but not any studies have reported association between BACE1 gene polymorphisms and seizures. Therefore, we investigated the possible association between focal seizures and BACE1 gene polymorphisms in the present study.Methods:A total of 162 patients and 211 health controls were enrolled in this study and polymorphisms of BACE1 gene were detected using polymerase chain reaction (PCR)-ligase detection reaction method.Results:The frequency of genotype AT for BACE1 rs535860 (A>T) was significantly higher (24.1%) in patients compared to controls (14.7%) (OR = 1.836, 95% CI = 1.086–3.102, P = .023). Intriguingly, we only found the significant difference of BACE1 SNP genotype and allele frequency among males but not females. However, no statistically significant results were presented for the genotype distributions of rs525493 (G>T) and rs638405(C>G) polymorphisms between patients and controls.Conclusion:Our study demonstrated there may exist an association between BACE1 rs535860 (A>T) polymorphism and focal seizures in Chinese Han males.